Neuroscience Journal The latest articles from Hindawi Publishing Corporation © 2016 , Hindawi Publishing Corporation . All rights reserved. The Progress of Mitophagy and Related Pathogenic Mechanisms of the Neurodegenerative Diseases and Tumor Tue, 08 Dec 2015 07:04:57 +0000 Mitochondrion, an organelle with two layers of membrane, is extremely vital to eukaryotic cell. Its major functions are energy center and apoptosis censor inside cell. The intactness of mitochondrial membrane is important to maintain its structure and function. Mitophagy is one kind of autophagy. In recent years, studies of mitochondria have shown that mitophagy is regulated by various factors and is an important regulation mechanism for organisms to maintain their normal state. In addition, abnormal mitophagy is closely related to several neurodegenerative diseases and tumor. However, the related signal pathway and its regulation mechanism still remain unclear. As a result, summarizing the progress of mitophagy and its related pathogenic mechanism not only helps to reveal the complicated molecular mechanism, but also helps to find a new target to treat the related diseases. Ying Song, Wei Ding, Yan Xiao, and Kong-jun Lu Copyright © 2015 Ying Song et al. All rights reserved. Fingolimod Real World Experience: Efficacy and Safety in Clinical Practice Thu, 26 Nov 2015 10:30:56 +0000 Fingolimod is a multiple sclerosis treatment licensed in Europe since 2011. Its efficacy has been demonstrated in three large phase III trials, used in the regulatory submissions throughout the world. As usual, in these trials the inclusion and exclusion criteria were designed to obtain a homogeneous population, with interchangeable characteristics in the different treatment arms. Although this is the best strategy to achieve a robust answer to the investigation question, it does not guaranty the treatment efficacy in the clinical practice, since in the real world there are concomitant treatments, comorbidities, adherence, and persistence challenges. But, to make informed treatment decision for a real life patient, we need to have evidence of the treatment efficacy, what has been called treatment effectiveness. This work aims to review fingolimod effectiveness, using, as source of information, abstracts, posters, and manuscripts. This unorthodox strategy was developed because more than half of the published experience with fingolimod is still on abstracts and posters. Only a small part of the studies reviewed are already published in peer reviewed journals. Fingolimod seems to be, at least, as effective and safe as it was on clinical trials, and with its long-term experience no new safety signals were observed. Joaquim Fonseca Copyright © 2015 Joaquim Fonseca. All rights reserved. Do Three Different Passive Assessments of Quadriceps Spasticity Relate to the Functional Activity of Walking for Children Diagnosed with Cerebral Palsy? Tue, 20 Oct 2015 09:41:59 +0000 A stiff-knee gait pattern is frequently associated with several impairments including quadriceps spasticity in children diagnosed with cerebral palsy (CP). The relationship of clinical measures of quadriceps spasticity and the stiff-knee gait pattern in children diagnosed with CP has not been well established. Therefore, the purpose of this study was to determine the ability of clinical measures of quadriceps spasticity (modified Ashworth scale [MAS], Ely tests, and pendulum test) to categorize a stiff-knee gait pattern in children with CP. Children were categorized as having a stiff-knee gait pattern based on kinematic and EMG gait data. Results of a logistic regression model revealed that the only significant measure was A1 of the pendulum test. Discriminant analysis functions were used to predict group membership (stiff-knee, not stiff-knee gait pattern) for each measure. The A1 of the pendulum test demonstrated the highest classification accuracy and the highest sensitivity compared to the other measures. Therefore, a negative pendulum test (indicated by an A1 value of 45 degrees or more) is more useful for ruling out a stiff-knee gait pattern compared to the other clinical measures. Hank White, Tim L. Uhl, and Sam Augsburger Copyright © 2015 Hank White et al. All rights reserved. Evaluation of Motor Neuron Excitability by CMAP Scanning with Electric Modulated Current Thu, 27 Aug 2015 06:08:15 +0000 Introduction. Compound Muscle Action Potential (CMAP) scan is a noninvasive promissory technique for neurodegenerative pathologies diagnosis. In this work new CMAP scan protocols were implemented to study the influence of electrical pulse waveform on peripheral nerve excitability. Methods. A total of 13 healthy subjects were tested. Stimulation was performed with an increasing intensities range from 4 to 30 mA. The procedure was repeated 4 times per subject, using a different single pulse stimulation waveform: monophasic square and triangular and quadratic and biphasic square. Results. Different waveforms elicit different intensity-response amplitude curves. The square pulse needs less current to generate the same response amplitude regarding the other waves and this effect is gradually decreasing for the triangular, quadratic, and biphasic pulse, respectively. Conclusion. The stimulation waveform has a direct influence on the stimulus-response slope and consequently on the motoneurons excitability. This can be a new prognostic parameter for neurodegenerative disorders. Tiago Araújo, Rui Candeias, Neuza Nunes, and Hugo Gamboa Copyright © 2015 Tiago Araújo et al. All rights reserved. Change in Motor and Nonmotor Symptoms Severity in a “Real-Life” Cohort of Subjects with Parkinson’s Disease Thu, 20 Aug 2015 16:14:12 +0000 Background. Parkinson’s disease (PD) is a chronic and progressive disorder. Rates of change in motor symptoms have been more studied compared to nonmotor symptoms. The objective was to describe these changes in a real-life cohort of subjects with PD. Methods. A cohort study was carried out from 2011 to 2013. Consecutive patients with PD were recruited from a movement disorders clinic. MDS-UPDRS, PDQ-8, and NMSS were applied to all subjects at an initial evaluation and a subsequent visit ( months). Disease severity was categorized using a recent classification of MDS-UPDRS severity. Results. The MDS-UPDRS Part III showed a significant decrease of points () between evaluations. A mean increase of points () in the MDS-UPDRS Part IV was observed. An increase of points () in the NMSS total score was found; when assessed individually, the difference was statistically significant only for the perceptual problems/hallucinations item. Quality of life remained unchanged. Conclusion. Motor improvement was observed accompanied by an increase in motor complications possibly as a result of treatment optimization. Nonmotor symptoms worsened as a whole. The overall effect in the quality of life was negligible. Adib Jorge de Saráchaga, Amin Cervantes-Arriaga, Rodrigo Llorens-Arenas, Humberto Calderón-Fajardo, and Mayela Rodríguez-Violante Copyright © 2015 Adib Jorge de Saráchaga et al. All rights reserved. Sex Differences and the Impact of Chronic Stress and Recovery on Instrumental Learning Thu, 16 Apr 2015 11:05:26 +0000 We have previously shown that 21-day chronic restraint stress impacts instrumental learning, but overall few studies have examined sex differences on the impact of stress on learning. We further examined sex differences in response to extended 42-day chronic stress on instrumental learning, as well as recovery from chronic stress. Rats were tested in aversive training tasks with or without prior appetitive experience, and daily body weight data was collected as an index of stress. Relative to control animals, reduced body weight was maintained from day 22 through day 42 across the stress period for males, but not for females. Stressed males had increased response speed and lower learning efficiency during appetitive acquisition and aversive learning. Males overall showed slower escape shaping times and more shock exposure. In contrast, stressed females showed slower appetitive response speeds and higher appetitive and aversive efficiency but overall reduced avoidance rates during acquisition and maintenance for transfer animals and during maintenance for aversive-only animals. These tasks reveal important nuances on the effect of stress on goal-directed behavior and further highlight sexually divergent effects on appetitive versus aversive motivation. Furthermore, these data underscore that systems are temporally impacted by chronic stress in a sexually divergent pattern. Angela L. McDowell, Kathryn M. H. Fransen, Kevin S. Elliott, Alhasan Elghouche, Polina V. Kostylev, Pamela K. O’Dea, and Preston E. Garraghty Copyright © 2015 Angela L. McDowell et al. All rights reserved. Motorcycle-Related Traumatic Brain Injuries: Helmet Use and Treatment Outcome Mon, 23 Mar 2015 09:14:15 +0000 Summary. With increasing use of motorcycle as means of transport in developing countries, traumatic brain injuries from motorcycle crashes have been increasing. The only single gadget that protects riders from traumatic brain injury is crash helmet. Objective. The objectives were to determine the treatment outcome among traumatic brain injury patients from motorcycle crashes and the rate of helmet use among them. Methods. It was a prospective, cross-sectional study of motorcycle-related traumatic brain injury patients managed in our center from 2010 to 2014. Patients were managed using our unit protocol for traumatic brain injuries. Data for the study were collected in accident and emergency, intensive care unit, wards, and outpatient clinic. The data were analyzed using Environmental Performance Index (EPI) info 7 software. Results. Ninety-six patients were studied. There were 87 males. Drivers were 65. Only one patient wore helmet. Majority of them were between 20 and 40 years. Fifty-three patients had mild head injuries. Favorable outcome among them was 84.35% while mortality was 12.5%. Severity of the injury affected the outcome significantly. Conclusion. Our study showed that the helmet use by motorcycle riders was close to zero despite the existing laws making its use compulsory in Nigeria. The outcome was related to severity of injuries. Mathias Ogbonna Nnanna Nnadi, Olufemi Babatola Bankole, and Beleudanyo Gbalipre Fente Copyright © 2015 Mathias Ogbonna Nnanna Nnadi et al. All rights reserved. Age- and Sex-Dependent Changes in Androgen Receptor Expression in the Developing Mouse Cortex and Hippocampus Tue, 03 Feb 2015 08:23:16 +0000 During the perinatal period, male mice are exposed to higher levels of testosterone (T) than females, which promotes sexual dimorphism in their brain structures and behaviors. In addition to acting via estrogen receptors after being locally converted into estradiol by aromatase, T also acts directly through androgen receptor (AR) in the brain. Therefore, we hypothesized that AR expression in the developing mouse cortex and hippocampus was sexually dimorphic. To test our hypothesis, we measured and determined AR mRNA and protein levels in mouse cortex/hippocampus collected on the day of birth (PN0) and 7 (PN7), 14 (PN14), and 21 (PN21) days after birth. We demonstrated that, as age advanced, AR mRNA levels increased in the cortex/hippocampus of both sexes but showed no sex difference. Two AR proteins, the full-length (110 kDa) and a smaller isoform (70 kDa), were detected in the developing mouse cortex/hippocampus with an age-dependent increase in protein levels of both AR isoforms at PN21 and a transient masculine increase in expression of the full-length AR protein on PN7. Thus, we conclude that the postnatal age and sex differences in AR protein expression in combination with the sex differences in circulating T may cause sexual differentiation of the mouse cortex/hippocampus. Houng-Wei Tsai, Saori Taniguchi, Jason Samoza, and Aaron Ridder Copyright © 2015 Houng-Wei Tsai et al. All rights reserved. Language Development across the Life Span: A Neuropsychological/Neuroimaging Perspective Thu, 18 Dec 2014 11:28:46 +0000 Language development has been correlated with specific changes in brain development. The aim of this paper is to analyze the linguistic-brain associations that occur from birth through senescence. Findings from the neuropsychological and neuroimaging literature are reviewed, and the relationship of language changes observable in human development and the corresponding brain maturation processes across age groups are examined. Two major dimensions of language development are highlighted: naming (considered a major measure of lexical knowledge) and verbal fluency (regarded as a major measure of language production ability). Developmental changes in the brain lateralization of language are discussed, emphasizing that in early life there is an increase in functional brain asymmetry for language, but that this asymmetry changes over time, and that changes in the volume of gray and white matter are age-sensitive. The effects of certain specific variables, such as gender, level of education, and bilingualism are also analyzed. General conclusions are presented and directions for future research are suggested. Mónica Rosselli, Alfredo Ardila, Esmeralda Matute, and Idaly Vélez-Uribe Copyright © 2014 Mónica Rosselli et al. All rights reserved. Impact of Age and Duration of Symptoms on Surgical Outcome of Single-Level Microscopic Anterior Cervical Discectomy and Fusion in the Patients with Cervical Spondylotic Radiculopathy Tue, 30 Sep 2014 14:08:21 +0000 We aim to evaluate the impact of age and duration of symptoms on surgical outcome of the patients with cervical spondylotic radiculopathy (CSR) who had been treated by single-level microscopic anterior cervical discectomy and fusion (ACDF). We retrospectively evaluated 68 patients (48 female and 20 male) with a mean age of (ranged from 24 to 72 years old) in our Orthopedic Department, Imam Reza Hospital. They were followed up for months (ranged from 25 to 65 months). Pain and disability were assessed by Visual Analogue Scale (VAS) and Neck Disability Index (NDI) questionnaires in preoperative and last follow-up visits. Functional outcome was eventually evaluated by Odom’s criteria. Surgery could significantly improve pain and disability from preoperative and to and (1–21) at the last follow-up visit, respectively. Satisfactory outcomes were observed in 89.7%. Symptom duration of more and less than six months had no effect on surgical outcome, but the results showed a statistically significant difference in NDI improvement in favor of the patients aged more than 45 years (), although pain improvement was similar in the two groups. Farzad Omidi-Kashani, Ebrahim Ghayem Hasankhani, and Reza Ghandehari Copyright © 2014 Farzad Omidi-Kashani et al. All rights reserved. Age-Dependent Increase of Absence Seizures and Intrinsic Frequency Dynamics of Sleep Spindles in Rats Mon, 23 Jun 2014 08:56:02 +0000 The risk of neurological diseases increases with age. In WAG/Rij rat model of absence epilepsy, the incidence of epileptic spike-wave discharges is known to be elevated with age. Considering close relationship between epileptic spike-wave discharges and physiologic sleep spindles, it was assumed that age-dependent increase of epileptic activity may affect time-frequency characteristics of sleep spindles. In order to examine this hypothesis, electroencephalograms (EEG) were recorded in WAG/Rij rats successively at the ages 5, 7, and 9 months. Spike-wave discharges and sleep spindles were detected in frontal EEG channel. Sleep spindles were identified automatically using wavelet-based algorithm. Instantaneous (localized in time) frequency of sleep spindles was determined using continuous wavelet transform of EEG signal, and intraspindle frequency dynamics were further examined. It was found that in 5-months-old rats epileptic activity has not fully developed (preclinical stage) and sleep spindles demonstrated an increase of instantaneous frequency from beginning to the end. At the age of 7 and 9 months, when animals developed matured and longer epileptic discharges (symptomatic stage), their sleep spindles did not display changes of intrinsic frequency. The present data suggest that age-dependent increase of epileptic activity in WAG/Rij rats affects intrinsic dynamics of sleep spindle frequency. Evgenia Sitnikova, Alexander E. Hramov, Vadim Grubov, and Alexey A. Koronovsky Copyright © 2014 Evgenia Sitnikova et al. All rights reserved. Association of Metabolic Syndrome and Inflammation with Cognitive Decline in Adults Aged 60 Years and Older: Findings from a National Health Survey in the United States Thu, 26 Dec 2013 18:35:25 +0000 Objectives. We aimed to test the hypothesis that metabolic syndrome (MetS) is significantly associated with cognitive decline (CoD) in elderly adults and further assess whether MetS and inflammation have a significant joint effect on CoD. Methods. Data () from the U.S. National Health and Nutrition Examination Survey (1999–2002) in participants aged ≥60 years who had Digit Symbol Substitution Tests (DSS: a standard measure of cognitive function) were studied. CoD was defined as those in the lowest quintile of DSS score. MetS was defined as having ≥3 of 5 MetS traits (large waist circumference (WC), high blood pressure (BP), elevated glucose, triglycerides, and decreased high density lipoprotein cholesterol). Results. Of 2975 participants, the prevalence of CoD (DSS score <25) was 12.1%. After adjusting covariates, individual large WC, high BP, elevated glucose level, and MetS were significantly associated with CoD in logistic regression models (). There was a significant dose-response relationship between an increased number of MetS traits and CoD (). A significant joint effect of MetS and CRP on the odds of CoD was observed. Conclusion. The study, using a nationally representative sample, extended previous studies by highlighting a significant MetS-CoD relationship and a joint effect of MetS and CRP on CoD. These novel findings add to our understanding of the association of neurometabolic disorders and cognition and have implications that may be relevant to primary care practice. Zuolu Liu and Carol F. Lippa Copyright © 2013 Zuolu Liu and Carol F. Lippa. All rights reserved. Brain SERT Expression of Male Rats Is Reduced by Aging and Increased by Testosterone Restitution Wed, 18 Dec 2013 10:04:26 +0000 In preclinical and clinical studies aging has been associated with a deteriorated response to antidepressant treatment. We hypothesize that such impairment is explained by an age-related decrease in brain serotonin transporter (SERT) expression associated with low testosterone (T) levels. The objectives of this study were to establish (1) if brain SERT expression is reduced by aging and (2) if the SERT expression in middle-aged rats is increased by T-restitution. Intact young rats (3–5 months) and gonad-intact middle-aged rats with or without T-restitution were used. The identification of the brain SERT expression was done by immunofluorescence in prefrontal cortex, lateral septum, hippocampus, and raphe nuclei. An age-dependent reduction of SERT expression was observed in all brain regions examined, while T-restitution recovered the SERT expression only in the dorsal raphe of middle-aged rats. This last action seems relevant since dorsal raphe plays an important role in the antidepressant action of selective serotonin reuptake inhibitors. All data suggest that this mechanism accounts for the T-replacement usefulness to improve the response to antidepressants in the aged population. José Jaime Herrera-Pérez, Alonso Fernández-Guasti, and Lucía Martínez-Mota Copyright © 2013 José Jaime Herrera-Pérez et al. All rights reserved. The mGlu2/3 Receptor Agonists LY354740 and LY379268 Differentially Regulate Restraint-Stress-Induced Expression of c-Fos in Rat Cerebral Cortex Tue, 19 Nov 2013 13:41:59 +0000 Metabotropic glutamate 2/3 (mGlu2/3) receptors have emerged as potential therapeutic targets due to the ability of mGlu2/3 receptor agonists to modulate excitatory transmission at specific synapses. LY354740 and LY379268 are selective and potent mGlu2/3 receptor agonists that show both anxiolytic- and antipsychotic-like effects in animal models. We compared the efficacy of LY354740 and LY379268 in attenuating restraint-stress-induced expression of the immediate early gene c-Fos in the rat prelimbic (PrL) and infralimbic (IL) cortex. LY354740 (10 and 30 mg/kg, i.p.) showed statistically significant and dose-related attenuation of stress-induced increase in c-Fos expression, in the rat cortex. By contrast, LY379268 had no effect on restraint-stress-induced c-Fos upregulation (0.3–10 mg/kg, i.p.). Because both compounds inhibit serotonin 2A receptor ()-induced c-Fos expression, we hypothesize that LY354740 and LY379268 have different in vivo properties and that activation and restraint stress induce c-Fos through distinct mechanisms. M. M. Menezes, M. A. Santini, M. J. Benvenga, G. J. Marek, K. M. Merchant, J. D. Mikkelsen, and K. A. Svensson Copyright © 2013 M. M. Menezes et al. All rights reserved. Detecting Silent Vocalizations in a Locked-In Subject Thu, 07 Nov 2013 13:52:23 +0000 Problem Addressed. Decoding of silent vocalization would be enhanced by detecting vocalization onset. This is necessary in order to improve decoding of neural firings and thus synthesize near conversational speech in locked-in subjects implanted with brain computer interfacing devices. Methodology. Cortical recordings were obtained during attempts at inner speech in a mute and paralyzed subject (ER) implanted with a recording electrode to detect and analyze lower beta band peaks meeting the criterion of a minimum 0.2% increase in the power spectrum density (PSD). To provide supporting data, three speaking subjects were used in a similar testing paradigm using EEG signals recorded over the speech area. Results. Conspicuous lower beta band peaks were identified around the time of assumed speech onset. The correlations between single unit firings, recorded at the same time as the continuous neural signals, were found to increase after the lower beta band peaks as compared to before the peaks. Studies in the nonparalyzed control individuals suggested that the lower beta band peaks were related to the movement of the articulators of speech (tongue, jaw, and lips), not to higher order speech processes. Significance and Potential Impact. The results indicate that the onset of silent and overt speech is associated with a sharp peak in lower beta band activity—an important step in the development of a speech prosthesis. This raises the possibility of using these peaks in online applications to assist decoding paradigms being developed to decode speech from neural signal recordings in mute humans. Elina Sarmah and Philip Kennedy Copyright © 2013 Elina Sarmah and Philip Kennedy. All rights reserved. Cognitive, Affective, and Motivational Changes during Ostracism: An ERP, EMG, and EEG Study Using a Computerized Cyberball Task Thu, 07 Nov 2013 08:35:08 +0000 Individuals are known to be highly sensitive to signs of ostracism, such as being ignored or excluded; however, the cognitive, affective, and motivational processes underlying ostracism have remained unclear. We investigated temporal changes in these psychological states resulting from being ostracized by a computer. Using event-related brain potentials (ERPs), the facial electromyogram (EMG), and electroencephalogram (EEG), we focused on the P3b amplitude, corrugator supercilii activity, and frontal EEG asymmetry, which reflect attention directed at stimuli, negative affect, and approach/withdrawal motivation, respectively. Results of the P3b and corrugator supercilii activity replicated findings of previous studies on being ostracized by humans. The mean amplitude of the P3b wave decreased, and facial EMG activity increased over time. In addition, frontal EEG asymmetry changed from relative left frontal activation, suggestive of approach motivation, to relative right frontal activation, indicative of withdrawal motivation. These findings suggest that ostracism by a computer-generated opponent is an aversive experience that in time changes the psychological status of ostracized people, similar to ostracism by human. Our findings also imply that frontal EEG asymmetry is a useful index for investigating ostracism. Results of this study suggest that ostracism has well developed neurobiological foundations. Taishi Kawamoto, Hiroshi Nittono, and Mitsuhiro Ura Copyright © 2013 Taishi Kawamoto et al. All rights reserved. Functional Outcomes of Surgery in Cervical Spondylotic Radiculopathy versus Myelopathy: A Comparative Study Sun, 18 Aug 2013 11:35:49 +0000 Background. Cervical spondylosis can cause three different categories of symptoms and signs with possible overlap in the affected patients. Aim. We aim to compare functional outcome of surgery in the patients with cervical spondylotic radiculopathy and myelopathy, regardless of their surgical type and approach. Materials and Methods. We retrospectively reviewed 140 patients with cervical spondylotic radiculopathy and myelopathy who had been operated from August 2006 to January 2011, as Group A (68 cases) and Group B (72 cases), respectively. The mean age was 48.2 and 55.7 years, while the mean followup was 38.9 and 37.3 months, respectively. Functional outcome of the patients was assessed by neck disability index (NDI) and patient satisfaction with surgery. Results. Only in Group A, the longer delay caused a worse surgical outcome (NDI). In addition, in Group B, there was no significant relationship between imaging signal change of the spinal cord and our surgical outcomes. Improvement in NDI and final satisfaction rate in both groups are comparable. Conclusions. Surgery was associated with an improvement in NDI in both groups (). The functional results in both groups were similar and comparable, regarding this index and patient's satisfaction score. F. Omidi-Kashani, E. G. Hasankhani, M. F. Vavsari, S. Afsari, and F. Golhasani-Keshtan Copyright © 2013 F. Omidi-Kashani et al. All rights reserved. Age-Induced Loss of Mossy Fibre Synapses on CA3 Thorns in the CA3 Stratum Lucidum Mon, 17 Jun 2013 15:13:54 +0000 Advanced ageing is associated with hippocampal deterioration and mild cognitive decline. The hippocampal subregion CA3 stratum lucidum (CA3-SL) receives neuronal inputs from the giant mossy fibre boutons of the dentate gyrus, but relatively little is known about the integrity of this synaptic connection with ageing. Using serial electron microscopy and unbiased stereology, we examined age-related changes in mossy fibre synapses on CA3 thorny excrescences within the CA3-SL of young adults (4-month-old), middle-aged (12-month-old), and old-aged (28-month-old) Wistar rats. Our data show that while there is an increase in CA3 volume with ageing, there is a significant (40–45%) reduction in synaptic density within the CA3-SL of 12- and 28-month-old animals compared with 4-month-old animals. We also present preliminary data showing that the CA3 neuropil in advanced ageing was conspicuously full of lipofuscin and phagolysosome positive, activated microglial cellular processes, and altered perivascular pathology. These data suggest that synaptic density in the CA3-SL is significantly impaired in ageing, accompanied by underlying prominent ultrastructural glial and microvascular changes. Bunmi Ojo, Heather Davies, Payam Rezaie, Paul Gabbott, Francis Colyer, Igor Kraev, and Michael G. Stewart Copyright © 2013 Bunmi Ojo et al. All rights reserved. Antinociceptive and Antioxidant Activities of Phytol In Vivo and In Vitro Models Tue, 11 Jun 2013 15:51:40 +0000 The objective of the present study was to evaluate the antinociceptive effects of phytol using chemical and thermal models of nociception in mice and to assess its antioxidant effects in vitro. Phytol was administered intraperitoneally (i.p.) to mice at doses of 25, 50, 100, and 200 mg/kg. In the acetic acid-induced writhing test, phytol significantly reduced the number of contortions compared to the control group (). In the formalin test, phytol reduced significantly the amount of time spent in paw licking in both phases (the neurogenic and inflammatory phases), this effect being more pronounced in the second phase (). Phytol also provoked a significant increase in latency in the hot plate test. These antinociceptive effects did not impaire the motor performance, as shown in the rotarod test. Phytol demonstrated a strong antioxidant effect in vitro in its capacity to remove hydroxyl radicals and nitric oxide as well as to prevent the formation of thiobarbituric acid reactive substances (TBARS). Taken as a whole, these results show the pronounced antinociceptive effects of phytol in the nociception models used, both through its central and peripheral actions, but also its antioxidant properties demonstrated in the in vitro methods used. Camila Carolina de Menezes Patrício Santos, Mirian Stiebbe Salvadori, Vanine Gomes Mota, Luciana Muratori Costa, Antonia Amanda Cardoso de Almeida, Guilherme Antônio Lopes de Oliveira, Jéssica Pereira Costa, Damião Pergentino de Sousa, Rivelilson Mendes de Freitas, and Reinaldo Nóbrega de Almeida Copyright © 2013 Camila Carolina de Menezes Patrício Santos et al. All rights reserved. Gene Network Analysis in Amygdala following Taste Aversion Learning in Rats Thu, 23 May 2013 18:02:24 +0000 Conditioned taste aversion (CTA) is an adaptive behavior that benefits survival of animals including humans and also serves as a powerful model to study the neural mechanisms of learning. Memory formation is a necessary component of CTA learning and involves neural processing and regulation of gene expression in the amygdala. Many studies have been focused on the identification of intracellular signaling cascades involved in CTA, but not late responsive genes underlying the long-lasting behavioral plasticity. In this study, we explored in silico experiments to identify persistent changes in gene expression associated with CTA in rats. We used oligonucleotide microarrays to identify 248 genes in the amygdala regulated by CTA. Pathway Studio and IPA software analyses showed that the differentially expressed genes in the amygdala fall in diverse functional categories such as behavior, psychological disorders, nervous system development and function, and cell-to-cell signaling. Conditioned taste aversion is a complex behavioral trait which involves association of visceral and taste inputs, consolidation of taste and visceral information, memory formation, retrieval of stored information, and extinction phase. In silico analysis of differentially expressed genes is therefore necessary to manipulate specific phase/stage of CTA to understand the molecular insight. Siva K. Panguluri, Nobuyuki Kuwabara, Nigel Cooper, Srinivas M. Tipparaju, Kevin B. Sneed, and Robert F. Lundy Copyright © 2013 Siva K. Panguluri et al. All rights reserved. Encoding into Visual Working Memory: Event-Related Brain Potentials Reflect Automatic Processing of Seemingly Redundant Information Sun, 12 May 2013 17:44:10 +0000 Encoding and maintenance of information in visual working memory in an S1-S2 task with a 1500 ms retention phase were investigated by means of event-related brain potentials (ERPs). Participants were asked to decide whether two visual stimuli were physically identical (identity comparison (IC) task) or belonged to the same set or category of equivalent patterns (category comparison (CC) task). The stimuli differ with regard to two features. (1) Each pattern can belong to a set of either four (ESS 4) or eight (ESS 8) equivalent patterns, mirroring differences in the complexity with regard to the representational structure of each pattern (i.e., equivalence set size (ESS)). (2) The set of patterns differ with regard to the rated complexity. Memory performance obtained the effects of the task instructions (IC versus CC) and the ESS (ESS 4 versus ESS 8) but not of the rated complexity. ERPs in the retention interval reveal that the stimulus-related factors (subjective complexity and ESS) affect the encoding of the stimuli as mirrored by the pronounced P3b amplitude in ESS 8 compared to ESS 4 patterns. Importantly, these effects are independent of task instructions. The pattern of results suggests an automatic processing of the ESS in the encoding phase. Stefan Berti and Urte Roeber Copyright © 2013 Stefan Berti and Urte Roeber. All rights reserved. The Modulation of Error Processing in the Medial Frontal Cortex by Transcranial Direct Current Stimulation Wed, 17 Apr 2013 16:06:21 +0000 Background. In order to prevent future errors, we constantly control our behavior for discrepancies between the expected (i.e., intended) and the real action outcome and continuously adjust our behavior accordingly. Neurophysiological correlates of this action-monitoring process can be studied with event-related potentials (error-related negativity (ERN) and error positivity (Pe)) originating from the medial prefrontal cortex (mPFC). Patients with neuropsychiatric diseases often show performance monitoring dysfunctions potentially caused by pathological changes of cortical excitability; therefore, a modulation of the underlying neuronal activity might be a valuable therapeutic tool. One technique which allows us to explore cortical modulation of neural networks is transcranial direct current stimulation (tDCS). Therefore, we tested the effect of medial-prefrontal tDCS on error-monitoring potentials in 48 healthy subjects randomly assigned to anodal, cathodal, or sham stimulation. Results. We found that cathodal stimulation attenuated Pe amplitudes compared to both anodal and sham stimulation, but no effect for the ERN. Conclusions. Our results indicate that cathodal tDCS over the mPFC results in an attenuated cortical excitability leading to decreased Pe amplitudes. We therefore conclude that tDCS has a neuromodulatory effect on error-monitoring systems suggesting a future approach to modify the sensitivity of corresponding neural networks in patients with action-monitoring deficits. Lisa Bellaïche, Manish Asthana, Ann-Christine Ehlis, Thomas Polak, and Martin J. Herrmann Copyright © 2013 Lisa Bellaïche et al. All rights reserved. Teratogenic Effect of Crude Ethanolic Root Bark and Leaf Extracts of Rauwolfia vomitoria (Apocynaceae) on Nissl Substances of Albino Wistar Rat Fetuses Sun, 24 Mar 2013 11:56:49 +0000 Rauwolfia vomitoria is a plant used for the treatment of insanity. The possible adverse effects of crude ethanolic root bark and leaf extract of the plant on Nissl substances of albino Wistar rat fetuses were studied using 25 mature female Wistar rats. The animals were divided equally into 5 groups, labeled A, B, C, D, and E. Group A was the control, while groups B, C, D, and E were the experimental. The female rats were mated with the males overnight, and the sperm positive day was designated as day zero of pregnancy. Oral doses of 150 mg/kg and 250 mg/kg body weight of the root bark extract were administered to groups B and C animals, respectively, while groups D and E animals received 150 mg/kg and 250 mg/kg body weight of the leaf extract, respectively, from day 7 to 11 of gestation. On day 20 of gestation, the rats were sacrificed, the fetuses brains extracted, and the cerebral cortices excised and routinely processed for Nissl substances using Cresyl fast violet staining method. Results showed reduced staining intensity of Nissl substances in the treated groups, especially those that received the root extract. Thus, the herbs may have adverse effects on protein synthesis within the cerebral cortex. Mokutima A. Eluwa, Theresa B. Ekanem, Paul B. Udoh, Moses B. Ekong, Olaitan R. Asuquo, Amabe O. Akpantah, and Agnes O. Nwakanma Copyright © 2013 Mokutima A. Eluwa et al. All rights reserved. Biochemical Evidence for a Putative Inositol 1,3,4,5-Tetrakisphosphate Receptor in the Olfactory System of Atlantic Salmon (Salmo salar) Mon, 11 Mar 2013 14:38:16 +0000 Olfactory receptor neurons in Atlantic salmon (Salmo salar) appear to use a phosphoinositide-directed phospholipase C (PLC) in odorant signal transduction. The consequences of odor-activated PLC depend on its product, inositol 1,4,5-trisphosphate (IP3). Therefore, a plasma membrane rich (PMR) fraction, previously characterized from salmon olfactory rosettes, was used to study binding sites for IP3 and its phosphorylation product, inositol 1,3,4,5-tetrakisphosphate (IP4). Binding sites for IP3 were present at the lower limit for detection in the PMR fraction but were abundant in a microsomal fraction. Binding sites for IP4 were abundant in the PMR fraction and thus colocalized in the same subcellular fraction with odorant receptors for amino acids and bile acids. Binding of IP4 was saturable and high affinity ( = 83 nM). The rank order for potency of inhibition of IP4 by other inositol polyphosphates (InsPx) followed the phosphorylation number with InsP6 > InsP5 > other InsP4 isomers > InsP3 isomers > InsP2 isomers, with the latter showing no activity. The consequences of PLC activity in this system may be dictated in part by a putative receptor for IP4. Jiongdong Pang and Dennis E. Rhoads Copyright © 2013 Jiongdong Pang and Dennis E. Rhoads. All rights reserved. The Effects of Sex and Chronic Restraint on Instrumental Learning in Rats Thu, 28 Feb 2013 14:52:21 +0000 Chronic stress has been shown to impact learning, but studies have been sparse or nonexistent examining sex or task differences. We examined the effects of sex and chronic stress on instrumental learning in adult rats. Rats were tested in an aversive paradigm with or without prior appetitive experience, and daily body weight data was collected as an index of stress. Relative to control animals, reduced body weight was maintained across the stress period for males (−7%, ) and females (−5%, ). For males, there were within-subject day-by-day differences after asymptotic transition, and all restrained males were delayed in reaching asymptotic performance. In contrast, stressed females were facilitated in appetitive and aversive-only instrumental learning but impaired during acquisition of the aversive transfer task. Males were faster than females in reaching the appetitive shaping criterion, but females were more efficient in reaching the appetitive tone-signaled criterion. Finally, an effect of task showed that while females reached aversive shaping criterion at a faster rate when they had prior appetitive learning, they were impaired in tone-signaled avoidance learning only when they had prior appetitive learning. These tasks reveal important nuances on the effect of stress and sex differences on goal-directed behavior. Angela L. McDowell, Kathryn M. Heath, and Preston E. Garraghty Copyright © 2013 Angela L. McDowell et al. All rights reserved. The Triglyceride Paradox in Stroke Survivors: A Prospective Study Mon, 25 Feb 2013 17:45:33 +0000 Objective. The purpose of our study was to understand the association between serum triglycerides and outcomes in acute ischemic stroke (AIS) patients. Methods. A cohort of all adult patients presenting to the Emergency Department (ED) with an AIS from March 2004 to December 2005 were selected. The lipid profile levels were measured within 24 hours of stroke onset. Demographics, admission stroke severity (NIHSS), functional outcome at discharge (modified Rankin Scale (mRS)), and mortality at 3 months were recorded. Results. The final cohort consisted of 334 subjects. A lower level of triglycerides at presentation was found to be significantly associated with worse National Institutes of Health Stroke Scale (NIHSS) (), worse mRS (), and death at 3 months (). After adjusting for age and gender and NIHSS, the association between triglyceride and mortality at 3 months was not significant (). Conclusion. Lower triglyceride levels seem to be associated with a worse prognosis in AIS. Minal Jain, Anunaya Jain, Neeraja Yerragondu, Robert D. Brown, Alejandro Rabinstein, Babak S. Jahromi, Lekshmi Vaidyanathan, Brian Blyth, and Latha Ganti Stead Copyright © 2013 Minal Jain et al. All rights reserved. rTMS as a Treatment of Alzheimer’s Disease with and without Comorbidity of Depression: A Review Thu, 07 Feb 2013 13:28:46 +0000 With an ever-increasing population of Alzheimer’s disease (AD) patients worldwide, a noninvasive treatment for AD is needed. In this paper, the application of repetitive transcranial magnetic stimulus (rTMS) as a treatment for patients with probable AD is compared to the application of rTMS as a treatment for depression. Comorbidity of depression and dementia is discussed, as well as possible links between the two diseases. The possible confounding antidepressant effects of rTMS on cognitive improvements in AD patients are discussed. Grant Rutherford, Rebecca Gole, and Zahra Moussavi Copyright © 2013 Grant Rutherford et al. All rights reserved. Roles of Integrins and Intracellular Molecules in the Migration and Neuritogenesis of Fetal Cortical Neurons: MEK Regulates Only the Neuritogenesis Sun, 20 Jan 2013 09:38:53 +0000 The roles of integrin subunits and intracellular molecules in regulating the migration and neuritogenesis of neurons isolated from 16.5 gestation days rat fetal cortices were examined using in vitro assays. Results showed that laminin supported the migration of fetal cortical neurons better than fibronectin and that the fetal cortical neurons migrated on laminin using β1 and α3 integrin subunits which make up the α3β1 integrin receptor. On fibronectin, the migration was mediated by β1 integrin subunit. Perturbation of src kinase, phospholipase C, or protein kinase C activity, inhibition of IP3 receptor mediated calcium release, or chelation of intracellular calcium inhibited both migration and neuritogenesis, whereas inhibition of growth factor signaling via MEK inhibited only the neuritogenesis. The detection of α1 and α9 transcripts suggested that the migration of fetal cortical neurons may also be mediated by α1β1 and α9β1 integrin receptors. Results showed that calcium may regulate migration and neuritogenesis by maintaining optimum levels of microtubules in the fetal cortical neurons. It is concluded that the fetal cortical neurons are fully equipped with the integrin signaling cascade required for their migration and neuritogenesis, whereas crosstalk between the integrin and growth-factor signaling regulate only the neuritogenesis. Ujjwal K. Rout Copyright © 2013 Ujjwal K. Rout. All rights reserved. Significance of Haemodynamic and Haemostatic Factors in the Course of Different Manifestations of Cerebral Small Vessel Disease: The SHEF-CSVD Study—Study Rationale and Protocol Wed, 02 Jan 2013 13:28:00 +0000 Rationale. This paper describes the rationale and design of the SHEF-CSVD Study, which aims to determine the long-term clinical and radiological course of cerebral small vessel disease (CSVD) and to evaluate haemostatic and haemodynamic prognostic factors of the condition. Design. This single-centre, prospective, non-interventional cohort study will follow 150 consecutive patients with different clinical manifestations of CSVD (lacunar ischaemic stroke, vascular dementia, vascular parkinsonism or spontaneous deep, intracerebral haemorrhage) and 50 age- and sex-matched controls over a period of 24 months. The clinical and radiological course will be evaluated basing on a detailed neurological, neuropsychological and MRI examinations. Haemodynamic (cerebral vasoreactivity, 24 h blood pressure control) and haemostatic factors (markers of endothelial and platelet dysfunction, brachial artery flow-mediated dilatation test) will be determined. Discussion. The scheduled study will specifically address the issue of haemodynamic and haemostatic prognostic factors and their course over time in various clinical manifestations of CSVD. The findings may aid the development of prophylactic strategies and individualised treatment plans, which are critical during the early stages of the disease. Jacek Staszewski, Renata Piusińska-Macoch, Ewa Skrobowska, Bogdan Brodacki, Rafał Pawlik, Tomasz Dutkiewicz, Wiesław Piechota, Alicja Rączka, Kazimierz Tomczykiewicz, and Adam Stępień Copyright © 2013 Jacek Staszewski et al. All rights reserved. Circadian Levels of Serum Melatonin and Cortisol in relation to Changes in Mood, Sleep, and Neurocognitive Performance, Spanning a Year of Residence in Antarctica Thu, 13 Dec 2012 14:33:47 +0000 Background. Altered circadian cortisol and melatonin rhythms in healthy subjects exposed to an extreme polar photoperiod results in changes in mood and sleep, which can influence cognitive performance. Materials and Methods. We assessed the circadian rhythm of 20 subjects who wintered over at Maitri (S, E), India’s permanent Antarctic station, from November 2010 to December 2011. Serum cortisol and melatonin levels were measured by radioimmunoassay at 8 am, 3 pm, 8 pm, and 2 am in a single day, once each during the polar summer and winter photoperiods. Conventional psychological tests, Depression, Anxiety, and Stress Scale (DASS-42), Epworth Sleepiness Scale (ESS), and a computerized neurocognitive test battery were used to measure mood, sleep, and cognitive performance. Results. The mean scores for DASS42 were higher during midwinter suggesting the presence of “overwintering.” Mean diurnal cortisol levels during summer and winter were comparable, but the levels of melatonin were markedly higher during winter. Higher 8 am melatonin levels were associated with better sleep quality, lower depression scores, and better performance in tasks like attention, visual memory, and arithmetic. Conclusion. Timing of artificial light exposure and usage of melatonin supplements in improving sleep and cognitive performance in expedition teams are of future research interest. Madhumita Premkumar, Tarulata Sable, Dinesh Dhanwal, and Richa Dewan Copyright © 2013 Madhumita Premkumar et al. All rights reserved.