Journal of Neurodegenerative Diseases http://www.hindawi.com The latest articles from Hindawi Publishing Corporation © 2014 , Hindawi Publishing Corporation . All rights reserved. Multidisciplinary Interventions in Motor Neuron Disease Tue, 18 Nov 2014 13:26:29 +0000 http://www.hindawi.com/journals/jnd/2014/435164/ Motor neuron disease is a neurodegenerative disease characterized by loss of upper motor neuron in the motor cortex and lower motor neurons in the brain stem and spinal cord. Death occurs 2–4 years after the onset of the disease. A complex interplay of cellular processes such as mitochondrial dysfunction, oxidative stress, excitotoxicity, and impaired axonal transport are proposed pathogenetic processes underlying neuronal cell loss. Currently evidence exists for the use of riluzole as a disease modifying drug; multidisciplinary team care approach to patient management; noninvasive ventilation for respiratory management; botulinum toxin B for sialorrhoea treatment; palliative care throughout the course of the disease; and Modafinil use for fatigue treatment. Further research is needed in management of dysphagia, bronchial secretion, pseudobulbar affect, spasticity, cramps, insomnia, cognitive impairment, and communication in motor neuron disease. U. E. Williams, E. E. Philip-Ephraim, and S. K. Oparah Copyright © 2014 U. E. Williams et al. All rights reserved. Nicotine-Cadmium Interaction Alters Exploratory Motor Function and Increased Anxiety in Adult Male Mice Thu, 13 Nov 2014 00:00:00 +0000 http://www.hindawi.com/journals/jnd/2014/359436/ In this study we evaluated the time dependence in cadmium-nicotine interaction and its effect on motor function, anxiety linked behavioural changes, serum electrolytes, and weight after acute and chronic treatment in adult male mice. Animals were separated randomly into four groups of n = 6 animals each. Treatment was done with nicotine, cadmium, or nicotine-cadmium for 21 days. A fourth group received normal saline for the same duration (control). Average weight was determined at 7-day interval for the acute (D1-D7) and chronic (D7-D21) treatment phases. Similarly, the behavioural tests for exploratory motor function (open field test) and anxiety were evaluated. Serum electrolytes were measured after the chronic phase. Nicotine, cadmium, and nicotine-cadmium treatments caused no significant change in body weight after the acute phase while cadmium-nicotine and cadmium caused a decline in weight after the chronic phase. This suggests the role of cadmium in the weight loss observed in tobacco smoke users. Both nicotine and cadmium raised serum Ca2+ concentration and had no significant effect on K+ ion when compared with the control. In addition, nicotine-cadmium treatment increased bioaccumulation of Cd2+ in the serum which corresponded to a decrease in body weight, motor function, and an increase in anxiety. Duyilemi Chris Ajonijebu, Philip Adeyemi Adeniyi, Adeshina Oloruntoba Adekeye, Babawale Peter Olatunji, Azeez Olakunle Ishola, and Olalekan Michael Ogundele Copyright © 2014 Duyilemi Chris Ajonijebu et al. All rights reserved. Comment on “Prevalence and Cognitive Bases of Subjective Memory Complaints in Older Adults: Evidence from a Community Sample” Wed, 13 Aug 2014 07:58:29 +0000 http://www.hindawi.com/journals/jnd/2014/240215/ Ashima Nehra, Sakshi Chopra, and Harsimarpreet Kaur Copyright © 2014 Ashima Nehra et al. All rights reserved. Glial Cell Line-Derived Neurotrophic Factor Family Members Reduce Microglial Activation via Inhibiting p38MAPKs-Mediated Inflammatory Responses Mon, 09 Jun 2014 09:15:47 +0000 http://www.hindawi.com/journals/jnd/2014/369468/ Previous studies have shown that glial cell line-derived neurotrophic factor (GDNF) family ligands (GFL) are potent survival factors for dopaminergic neurons and motoneurons with therapeutic potential for Parkinson’s disease. However, little is known about direct influences of the GFL on microglia function, which are known to express part of the GDNF receptor system. Using RT-PCR and immunohistochemistrym we investigated the expression of the GDNF family receptor alpha 1 (GFR alpha) and the coreceptor transmembrane receptor tyrosine kinase (RET) in rat microglia in vitro as well as the effect of GFL on the expression of proinflammatory molecules in LPS activated microglia. We could show that GFL are able to regulate microglia functions and suggest that part of the well known neuroprotective action may be related to the suppression of microglial activation. We further elucidated the functional significance and pathophysiological implications of these findings and demonstrate that microglia are target cells of members of the GFL (GDNF and the structurally related neurotrophic factors neurturin (NRTN), artemin (ARTN), and persephin (PSPN)). Uta Rickert, Steffen Grampp, Henrik Wilms, Jessica Spreu, Friederike Knerlich-Lukoschus, Janka Held-Feindt, and Ralph Lucius Copyright © 2014 Uta Rickert et al. All rights reserved. Prevalence and Cognitive Bases of Subjective Memory Complaints in Older Adults: Evidence from a Community Sample Sun, 27 Apr 2014 09:55:47 +0000 http://www.hindawi.com/journals/jnd/2014/176843/ Objectives. To estimate the prevalence of subjective memory complaints (SMCs) in a sample of community-dwelling, older adults and to examine cognitive bases of these complaints. Participants. 499 community-dwelling adults, 65 and older. Measurements. A telephone survey consisting of cognitive tests and clinical and sociodemographic variables. SMCs were based on subjects' evaluations and subjects' perceptions of others' evaluations. Analysis. Logistic regression was used to model the risk for SMCs as a function of the cognitive, clinical, and sociodemographic variables. We tested for interactions of the cognitive variables with age, education, and gender. Results. 27.1% reported memory complaints. Among the younger age, better objective memory performance predicted lower risk for SMCs, while among the older age, better memory had no effect on risk. Among the better-educated people, better global cognitive functioning predicted lower risk for SMCs, while among the less-educated people, better global cognitive functioning had no effect on SMC risk. When predicting others' perceptions, better objective memory was associated with lower risk for SMCs. Conclusion. Objective memory performance and global cognitive functioning are associated with lower risk for SMCs, but these relationships are the strongest for the younger age and those with more education, respectively. Age and education may affect the ability to accurately appraise cognitive functioning. Thomas Fritsch, McKee J. McClendon, Maggie S. Wallendal, Trevor F. Hyde, and Janet D. Larsen Copyright © 2014 Thomas Fritsch et al. All rights reserved. Essential Tremor in the Elderly and Risk for Dementia Wed, 09 Apr 2014 08:43:04 +0000 http://www.hindawi.com/journals/jnd/2014/328765/ The objective is to examine the risk of dementia in subjects with essential tremor (ET) involved in the Arizona Study of Aging and Neurodegenerative Disorders. All subjects were free of a neurodegenerative diagnosis at baseline and had annual motor, general neurological, and neuropsychological assessments. Subjects with ET were compared with controls for the risk of dementia. There were 83 subjects with ET and 424 subjects without tremor. Mean age at study entry was for ET and for controls. Median tremor duration was 5.2 years at study entry. Followup was a median of 5.4 years (range 0.9 to 12.1). The hazard ratio for the association between ET and dementia was 0.79 (95% CI 0.33 to 1.85). The hazard ratio for the association between tremor onset at age 65 or over, versus onset before age 65, was 2.1 (95% CI 0.24 to 18) and the hazard ratio for the association between tremor duration greater than 5 years, versus less than 5 years, was 0.46 (95% CI 0.08 to 2.6). We conclude that all elderly ET was not associated with an increased risk of dementia but that a subset of subjects with older age onset/shorter duration tremor may be at higher risk. Holly A. Shill, Joseph G. Hentz, Sandra A. Jacobson, Christine Belden, Marwan N. Sabbagh, Thomas G. Beach, Erika Driver-Dunckley, and Charles H. Adler Copyright © 2014 Holly A. Shill et al. All rights reserved. Differential Changes in Postsynaptic Density Proteins in Postmortem Huntington’s Disease and Parkinson’s Disease Human Brains Thu, 16 Jan 2014 08:38:27 +0000 http://www.hindawi.com/journals/jnd/2014/938530/ NMDA and AMPA-type glutamate receptors and their bound membrane-associated guanylate kinases (MAGUKs) are critical for synapse development and plasticity. We hypothesised that these proteins may play a role in the changes in synapse function that occur in Huntington’s disease (HD) and Parkinson’s disease (PD). We performed immunohistochemical analysis of human postmortem brain tissue to examine changes in the expression of SAP97, PSD-95, GluA2 and GluN1 in human control, and HD- and PD-affected hippocampus and striatum. Significant increases in SAP97 and PSD-95 were observed in the HD and PD hippocampus, and PSD95 was downregulated in HD striatum. We observed a significant increase in GluN1 in the HD hippocampus and a decrease in GluA2 in HD and PD striatum. Parallel immunohistochemistry experiments in the YAC128 mouse model of HD showed no change in the expression levels of these synaptic proteins. Our human data show that major but different changes occur in glutamatergic proteins in HD versus PD human brains. Moreover, the changes in human HD brains differ from those occurring in the YAC128 HD mouse model, suggesting that unique changes occur at a subcellular level in the HD human hippocampus. C. Fourie, E. Kim, H. Waldvogel, J. M. Wong, A. McGregor, R. L. M. Faull, and J. M. Montgomery Copyright © 2014 C. Fourie et al. All rights reserved. Outcomes of a Peer Support Program in Multiple Sclerosis in an Australian Community Cohort: A Prospective Study Thu, 05 Dec 2013 15:52:39 +0000 http://www.hindawi.com/journals/jnd/2013/429171/ Background/Objectives. This pilot study evaluated the impact of a peer support program on improving multiple sclerosis (MS) related psychological functions (depression, anxiety, and stress) and enhancing quality of life. Methodology. Participants () were recruited prospectively and received an 8-week group face-to-face peer support program. Assessments were at baseline (T1), 6 weeks after program (T2), and 12 months after program (T3), using validated questionnaires: Depression Anxiety Stress Scale (DASS), McGill Quality of Life (MQOL), and Brief COPE. Results. Participants’ mean age was 52; the majority were female (64%) and married (64%). Median time since MS diagnosis was 16 years. At T2, participants reported improved psychological functioning (DASS “depression,” “anxiety,” and “stress” subscales, values −2.36, −2.22, and −2.54, moderate effect sizes () 0.29, 0.28, and 0.32, resp.) and quality of life (MQOL SIS score −2.07, ) and were less likely to use “self-blame” as a coping mechanism (Brief COPE score −2.37, ). At T3, the positive improvements in stress (DASS stress subscale score −2.41, ) and quality of life were maintained (MQOL SIS, score −2.30, ). There were no adverse effects reported. Louisa Ng, Bhasker Amatya, and Fary Khan Copyright © 2013 Louisa Ng et al. All rights reserved. Neuroprotection by Exendin-4 Is GLP-1 Receptor Specific but DA D3 Receptor Dependent, Causing Altered BrdU Incorporation in Subventricular Zone and Substantia Nigra Thu, 21 Nov 2013 14:17:39 +0000 http://www.hindawi.com/journals/jnd/2013/407152/ Glucagon-like peptide-1 receptor (GLP-1R) activation by exendin-4 (EX-4) is effective in preclinical models of Parkinson’s disease (PD) and appears to promote neurogenesis even in severely lesioned rats. In the present study, we determined the effects of EX-4 on cellular BrdU incorporation in the rat subventricular zone (SVZ) and substantia nigra (SN). We also determined the specificity of this effect with the GLP-1R antagonist EX-(9-39) as well as the potential role of dopamine (DA) D3 receptors. Rats were administered 6-OHDA and 1 week later given EX-4 alone, with EX-(9-39) or nafadotride (D3 antagonist) and BrdU. Seven days later, rats were challenged with apomorphine to evaluate circling. Extracellular DA was measured using striatal microdialysis and subsequently tissue DA measured. Tyrosine hydroxylase and BrdU were verified using immunohistochemistry. Apomorphine circling was reversed by EX-4 in lesioned rats, an effect reduced by EX-4, while both EX-(9-39) and NAF attenuated this. 6-OHDA decreased extracellular and tissue DA, both reversed by EX-4 but again attenuated by EX-(9-39) or NAF. Analysis of BrdU+ cells in the SVZ revealed increases in 6-OHDA-treated rats which were reversed by EX-4 and antagonised by either EX-(9-39) or NAF, while in the SN the opposite profile was seen. A. Harkavyi, N. Rampersaud, and P. S. Whitton Copyright © 2013 A. Harkavyi et al. All rights reserved. Simple Repeat-Primed PCR Analysis of the Myotonic Dystrophy Type 1 Gene in a Clinical Diagnostics Environment Mon, 11 Nov 2013 13:56:05 +0000 http://www.hindawi.com/journals/jnd/2013/857564/ Myotonic dystrophy type 1 is an autosomal dominant neuromuscular disorder that is caused by the expansion of a CTG trinucleotide repeat in the DMPK gene. The confirmation of a clinical diagnosis of DM-1 usually involves PCR amplification of the CTG repeat-containing region and subsequent sizing of the amplification products in order to deduce the number of CTG repeats. In the case of repeat hyperexpansions, Southern blotting is also used; however, the latter has largely been superseded by triplet repeat-primed PCR (TP-PCR), which does not yield a CTG repeat number but nevertheless provides a means of stratifying patients regarding their disease severity. We report here a combination of forward and reverse TP-PCR primers that allows for the simple and effective scoring of both the size of smaller alleles and the presence or absence of expanded repeat sequences. In addition, the CTG repeat-containing TP-PCR forward primer can target both the DM-1 and Huntington disease genes, thereby streamlining the work flow for confirmation of clinical diagnoses in a diagnostic laboratory. Philippa A. Dryland, Elaine Doherty, Jennifer M. Love, and Donald R. Love Copyright © 2013 Philippa A. Dryland et al. All rights reserved. Sleep-Wake Cycle and Daytime Sleepiness in the Myotonic Dystrophies Mon, 04 Nov 2013 15:05:34 +0000 http://www.hindawi.com/journals/jnd/2013/692026/ Myotonic dystrophy is the most common type of muscular dystrophy in adults and is characterized by progressive myopathy, myotonia, and multiorgan involvement. Two genetically distinct entities have been identified, myotonic dystrophy type 1 (DM1 or Steinert’s Disease) and myotonic dystrophy type 2 (DM2). Myotonic dystrophies are strongly associated with sleep dysfunction. Sleep disturbances in DM1 are common and include sleep-disordered breathing (SDB), periodic limb movements (PLMS), central hypersomnia, and REM sleep dysregulation (high REM density and narcoleptic-like phenotype). Interestingly, drowsiness in DM1 seems to be due to a central dysfunction of sleep-wake regulation more than SDB. To date, little is known regarding the occurrence of sleep disorders in DM2. SDB (obstructive and central apnoea), REM sleep without atonia, and restless legs syndrome have been described. Further polysomnographic, controlled studies are strongly needed, particularly in DM2, in order to clarify the role of sleep disorders in the myotonic dystrophies. A. Romigi, M. Albanese, C. Liguori, F. Placidi, M. G. Marciani, and R. Massa Copyright © 2013 A. Romigi et al. All rights reserved. Death Receptors in the Selective Degeneration of Motoneurons in Amyotrophic Lateral Sclerosis Tue, 16 Jul 2013 14:31:26 +0000 http://www.hindawi.com/journals/jnd/2013/746845/ While studies on death receptors have long been restricted to immune cells, the last decade has provided a strong body of evidence for their implication in neuronal death and hence neurodegenerative disorders such as amyotrophic lateral sclerosis (ALS). ALS is a fatal paralytic disorder that primarily affects motoneurons in the brain and spinal cord. A neuroinflammatory process, associated with astrocyte and microglial activation as well as infiltration of immune cells, accompanies motoneuron degeneration and supports the contribution of non-cell-autonomous mechanisms in the disease. Hallmarks of Fas, TNFR, LT-βR, and p7 signaling have been observed in both animal models and ALS patients. This review summarizes to date knowledge of the role of death receptors in ALS and the link existing between the selective loss of motoneurons and neuroinflammation. It further suggests how this recent evidence could be included in an ultimate multiapproach to treat patients. Julianne Aebischer, Nathalie Bernard-Marissal, Brigitte Pettmann, and Cédric Raoul Copyright © 2013 Julianne Aebischer et al. All rights reserved. Immunolocalization of Kisspeptin Associated with Amyloid-β Deposits in the Pons of an Alzheimer’s Disease Patient Thu, 16 May 2013 09:47:13 +0000 http://www.hindawi.com/journals/jnd/2013/879710/ The pons region of the Alzheimer’s disease (AD) brain is one of the last to show amyloid-β (Aβ) deposits and has been suggested to contain neuroprotective compounds. Kisspeptin (KP) is a hormone that activates the hypothalamic-pituitary-gonadal axis and has been suggested to be neuroprotective against Aβ toxicity. The localization of KP, plus the established endogenous neuroprotective compounds corticotropin releasing hormone (CRH) and catalase, in tissue sections from the pons region of a male AD subject has been determined in relation to Aβ deposits. Results showed Aβ deposits also stained with KP, CRH, and catalase antibodies. At high magnification the staining of deposits was either KP or catalase positive, and there was only a limited area of the deposits with KP-catalase colocalization. The CRH does not bind Aβ, whilst both KP and catalase can bind Aβ, suggesting that colocalization in Aβ deposits is not restricted to compounds that directly bind Aβ. The neuroprotective actions of KP, CRH, and catalase were confirmed in vitro, and fibrillar Aβ preparations were shown to stimulate the release of KP in vitro. In conclusion, neuroprotective KP, CRH, and catalase all colocalize with Aβ plaque-like deposits in the pons region from a male AD subject. Amrutha Chilumuri, Maria Ashioti, Amanda N. Nercessian, and Nathaniel G. N. Milton Copyright © 2013 Amrutha Chilumuri et al. All rights reserved. Obstacle Avoidance amongst Parkinson Disease Patients Is Challenged in a Threatening Context Wed, 15 May 2013 11:44:20 +0000 http://www.hindawi.com/journals/jnd/2013/787861/ We examined whether people with Parkinson disease (PD) have difficulty negotiating a gait obstruction in threatening (gait path and obstacle raised above floor) and nonthreatening (gait path and obstacle at floor level) contexts. Ten PD patients were tested in both Meds OFF and Meds ON states, along with 10 age-matched controls. Participants completed 18 gait trials, walking 4.7 m at a self-selected speed while attempting to cross an obstacle 0.15 m in height placed near the centre point of the walkway. Kinematic and kinetic parameters were measured, and obstacle contact errors were tallied. Results indicated that PD patients made more obstacle contacts than control participants in the threatening context. Successful crossings by PD patients in the threatening condition also exhibited kinematic differences, with Meds OFF PD patients making shorter crossing steps, with decreased initiation and crossing velocities. The findings from this study lend support to the theory that PD patients rely on directed attention to initiate and control movement, while providing indication that the motor improvements provided by current PD pharmacotherapy may be limited by contextual interference. These movement patterns may be placing PD patients at risk of obstacle contact and falling. Jon B. Doan, Natalie de Bruin, Sergio M. Pellis, Oksana Suchowersky, Ian Q. Whishaw, and Lesley A. Brown Copyright © 2013 Jon B. Doan et al. All rights reserved. Reevaluating Metabolism in Alzheimer's Disease from the Perspective of the Astrocyte-Neuron Lactate Shuttle Model Tue, 23 Apr 2013 16:23:32 +0000 http://www.hindawi.com/journals/jnd/2013/234572/ The conventional view of central nervous system (CNS) metabolism is based on the assumption that glucose is the main fuel source for active neurons and is processed in an oxidative manner. However, since the early 1990s research has challenged the idea that the energy needs of nerve cells are met exclusively by glucose and oxidative metabolism. This alternative view of glucose utilization contends that astrocytes metabolize glucose to lactate, which is then released and taken up by nearby neurons and used as a fuel source, commonly known as the astrocyte-neuron lactate shuttle (ANLS) model. Once thought of as a waste metabolite, lactate has emerged as a central player in the maintenance of neuronal function and long-term memory. Decreased neuronal metabolism has traditionally been viewed as a hallmark feature of Alzheimer's disease (AD). However, a more complex picture of CNS metabolism is emerging that may provide valuable insight into the pathophysiological changes that occur during AD and other neurodegenerative diseases. This review will examine the ANLS model and present recent evidence highlighting the critical role that lactate plays in neuronal survival and memory. Moreover, the role of glucose and lactate metabolism in AD will be re-evaluated from the perspective of the ANLS. Jordan T. Newington, Richard A. Harris, and Robert C. Cumming Copyright © 2013 Jordan T. Newington et al. All rights reserved. P-Glycoprotein Altered Expression in Alzheimer's Disease: Regional Anatomic Variability Wed, 03 Apr 2013 11:48:36 +0000 http://www.hindawi.com/journals/jnd/2013/257953/ We investigated the expression of P-glycoprotein (P-gp) in brain samples of Alzheimer disease (AD) and normative brains (NM). Superior temporal cortex hippocampal and brainstem samples from 15 AD and NM brains were selected from comparable sites. P-gp positive capillaries and β-amyloid (Aβ) senile plaques (SP) were counted. Statistical analysis of the data was performed using nonparametric data analysis with Mann-Whitney, Kruskal-Wallis, and Spearman’s tests. There were no significant differences in P-gp expression between superior temporal and hippocampus samples. However, there were significant differences in P-gp expression, when comparing brainstem with both hippocampal and superior temporal samples in both conditions (; in NM cases and ; in AD cases); the brainstem has greater P-gp expression in each case and condition. In addition, there was a notable inverse negative correlation () between P-gp expression and the presence of SPs in the AD condition superior temporal cortex. The results of this study suggest that there were significant site-dependent differences in the expression of P-gp. There may be an increased protective role for P-gp expression against amyloid deposition in the brainstem and in the superior temporal cortex of AD brains. Brian Jeynes and John Provias Copyright © 2013 Brian Jeynes and John Provias. All rights reserved. The Effect of Lipoic Acid Therapy on Cognitive Functioning in Patients with Alzheimer's Disease Sat, 30 Mar 2013 11:23:54 +0000 http://www.hindawi.com/journals/jnd/2013/454253/ Diabetes mellitus (DM) is an important risk factor for Alzheimer's disease (AD). Most diabetic patients have insulin resistance (IR) that is associated with compensatory hyperinsulinemia, one of the mechanisms suggested for increased AD risk in patients with DM. Alpha-lipoic acid (ALA) is a disulfide molecule with antioxidant properties that has positive effects on glucose metabolism and IR. This study evaluated the effect of ALA treatment (600 mg/day) on cognitive performances in AD patients with and without DM. One hundred and twenty-six patients with AD were divided into two groups, according to DM presence (group A) or absence (group B). Cognitive functions were assessed by MMSE, Alzheimer's Disease Assessment Scale-cognitive (ADAS-Cog), Clinician's Interview-Based Impression of Severity (CIBIC), Clinical Dementia Rating (CDR), and Alzheimer's Disease Functional and Change Scale (ADFACS). IR was assessed by HOMA index. At the end of the study, MMSE scores showed a significant improvement in 43% patients of group A (26 subjects) and 23% of group B (15 subjects), compared to baseline (). Also ADAS-Cog, CIBIC, and ADFACS scores showed a significant improvement in group A versus group B. IR was higher in group A. Our study suggests that ALA therapy could be effective in slowing cognitive decline in patients with AD and IR. Antonietta Fava, Domenico Pirritano, Massimiliano Plastino, Dario Cristiano, Giovanna Puccio, Carmen Colica, Caterina Ermio, Matteo De Bartolo, Gaetano Mauro, and Domenico Bosco Copyright © 2013 Antonietta Fava et al. All rights reserved. Cerebrospinal Fluid Biomarkers for Kii Amyotrophic Lateral Sclerosis/Parkinsonism-Dementia Complex Wed, 27 Mar 2013 10:59:10 +0000 http://www.hindawi.com/journals/jnd/2013/679089/ Objective. Amyotrophic lateral sclerosis/parkinsonism-dementia complex is classified as one of the tauopathies. Methods. The total tau, phosphorylated tau, and amyloid β42 levels were assayed in cerebrospinal fluid from patients with Kii amyotrophic lateral sclerosis/parkinsonism-dementia complex (), Alzheimer’s disease (), Parkinson’s disease (), amyotrophic lateral sclerosis (), and controls () using specific enzyme-linked immunosorbent assay methods. Results. Total tau and phosphorylated tau did not increase and amyloid β42 was relatively reduced in Kii amyotrophic lateral sclerosis/parkinsonism-dementia complex. Relatively reduced amyloid β42 might discriminate Kii amyotrophic lateral sclerosis/parkinsonism-dementia complex from amyotrophic lateral sclerosis and Parkinson’s disease, and the ratios of phosphorylated-tau to amyloid β42 could discriminate Kii amyotrophic lateral sclerosis/parkinsonism-dementia complex from Alzheimer’s disease. Conclusions. Cerebrospinal fluid analysis may be useful to differentiate amyotrophic lateral sclerosis/parkinsonism-dementia complex from Alzheimer’s disease, amyotrophic lateral sclerosis, and Parkinson’s disease. Yui Nakayama, Satoru Morimoto, Misao Yoneda, Shigeki Kuzuhara, and Yasumasa Kokubo Copyright © 2013 Yui Nakayama et al. All rights reserved. Clinical and Genetic Study of Algerian Patients with Spinal Muscular Atrophy Sun, 24 Mar 2013 13:29:01 +0000 http://www.hindawi.com/journals/jnd/2013/903875/ Spinal muscular atrophy (SMA) is the second most common lethal autosomal recessive disorder. It is divided into the acute Werdnig-Hoffmann disease (type I), the intermediate form (type II), the Kugelberg-Welander disease (type III), and the adult form (type IV). The gene involved in all four forms of SMA, the so-called survival motor neuron (SMN) gene, is duplicated, with a telomeric (tel SMN or SMN1) and a centromeric copy (cent SMN or SMN2). SMN1 is homozygously deleted in over 95% of SMA patients. Another candidate gene in SMA is the neuronal apoptosis inhibitory protein (NAIP) gene; it shows homozygous deletions in 45–67% of type I and 20–42% of type II/type III patients. Here we studied the SMN and NAIP genes in 92 Algerian SMA patients (20 type I, 16 type II, 53 type III, and 3 type IV) from 57 unrelated families, using a semiquantitative PCR approach. Homozygous deletions of SMN1 exons 7 and/or 8 were found in 75% of the families. Deletions of exon 4 and/or 5 of the NAIP gene were found in around 25%. Conversely, the quantitative analysis of SMN2 copies showed a significant correlation between SMN2 copy number and the type of SMA. Y. Sifi, K. Sifi, A. Boulefkhad, N. Abadi, Z. Bouderda, R. Cheriet, M. Magen, J. P. Bonnefont, A. Munnich, C. Benlatreche, and A. Hamri Copyright © 2013 Y. Sifi et al. All rights reserved. Increasing Membrane Cholesterol Level Increases the Amyloidogenic Peptide by Enhancing the Expression of Phospholipase C Thu, 07 Mar 2013 14:01:24 +0000 http://www.hindawi.com/journals/jnd/2013/407903/ Cerebral elevation of 42-residue amyloid β-peptide (Aβ42) triggers neuronal dysfunction in Alzheimer's disease (AD). Even though a number of cholesterol modulating agents have been shown to affect Aβ generation, the role of cholesterol in the pathogenesis of AD is not clear yet. Recently, we have shown that increased membrane cholesterol levels downregulates phosphatidylinositol 4,5-bisphosphate (PIP2) via activation of phospholipase C (PLC). In this study, we tested whether membrane cholesterol levels may affect the Aβ42 production via changing PIP2 levels. Increasing membrane cholesterol levels decreased PIP2 and increased secreted Aβ42. Supplying PIP2, by using a PIP2-carrier system, blocked the effect of cholesterol on Aβ42. We also found that cholesterol increased the expressions of β1 and β3 PLC isoforms (PLCβ1, PLCβ3). Silencing the expression of PLCβ1 prevented the effects of cholesterol on PIP2 levels as well as on Aβ42 production, suggesting that increased membrane cholesterol levels increased secreted Aβ42 by downregulating PIP2 via enhancing the expression of PLCβ1. Thus, cholesterol metabolism may be linked to Aβ42 levels via PLCβ1 expression and subsequent changes in PIP2 metabolism. Yoon Sun Chun, Hyun Geun Oh, Myoung Kyu Park, Tae-Wan Kim, and Sungkwon Chung Copyright © 2013 Yoon Sun Chun et al. All rights reserved. Bacopa monnieri Phytochemicals Mediated Synthesis of Platinum Nanoparticles and Its Neurorescue Effect on 1-Methyl 4-Phenyl 1,2,3,6 Tetrahydropyridine-Induced Experimental Parkinsonism in Zebrafish Mon, 04 Mar 2013 13:19:09 +0000 http://www.hindawi.com/journals/jnd/2013/972391/ Current discovery demonstrates the rapid formation of platinum nanoparticles using leaf extract of a neurobeneficial plant, Bacopa monnieri (BmE). The nanoparticles (BmE-PtNPs) were stabilized and then coated with varied phytochemicals present within the leaf extract. These nanoparticles demonstrated the same activity of Complex I, as that of oxidizing NADH to NAD+ using a spectrophotometric method. This suggests that BmE-PtNPs are a potential medicinal substance for oxidative stress mediated disease with suppressed mitochondrial complex I, namely, Parkinson's disease (PD). Hence, the neuroprotective potentials of the phytochemical coated nanoparticle were explored in 1-methyl 4-phenyl 1,2,3,6 tetrahydropyridine- (MPTP-)induced experimental Parkinsonism in zebrafish model. BmE-PtNPs pretreatment significantly reversed toxic effects of MPTP by increasing the levels of dopamine, its metabolites, GSH and activities of GPx, catalase, SOD and complex I, and reducing levels of MDA along with enhanced locomotor activity. Taken together, these findings suggest that BmE-PtNPs have protective effect in MPTP-induced neurotoxicity in this model of Parkinson's disease via their dual functions as mitochondrial complex I and antioxidant activity. Jayshree Nellore, Cynthia Pauline, and Kanchana Amarnath Copyright © 2013 Jayshree Nellore et al. All rights reserved. Amyloid Beta-Protein and Neural Network Dysfunction Wed, 30 Jan 2013 10:50:49 +0000 http://www.hindawi.com/journals/jnd/2013/657470/ Understanding the neural mechanisms underlying brain dysfunction induced by amyloid beta-protein (Aβ) represents one of the major challenges for Alzheimer’s disease (AD) research. The most evident symptom of AD is a severe decline in cognition. Cognitive processes, as any other brain function, arise from the activity of specific cell assemblies of interconnected neurons that generate neural network dynamics based on their intrinsic and synaptic properties. Thus, the origin of Aβ-induced cognitive dysfunction, and possibly AD-related cognitive decline, must be found in specific alterations in properties of these cells and their consequences in neural network dynamics. The well-known relationship between AD and alterations in the activity of several neural networks is reflected in the slowing of the electroencephalographic (EEG) activity. Some features of the EEG slowing observed in AD, such as the diminished generation of different network oscillations, can be induced in vivo and in vitro upon Aβ application or by Aβ overproduction in transgenic models. This experimental approach offers the possibility to study the mechanisms involved in cognitive dysfunction produced by Aβ. This type of research may yield not only basic knowledge of neural network dysfunction associated with AD, but also novel options to treat this modern epidemic. Fernando Peña-Ortega Copyright © 2013 Fernando Peña-Ortega. All rights reserved. Sex Differences in Presynaptic Density and Neurogenesis in Middle-Aged ApoE4 and ApoE Knockout Mice Sun, 27 Jan 2013 14:03:11 +0000 http://www.hindawi.com/journals/jnd/2013/531326/ Atherosclerosis and apolipoprotein E ε4 (APOE4) genotype are risk factors for Alzheimer’s disease (AD) and cardiovascular disease (CVD). Sex differences exist in prevalence and manifestation of both diseases. We investigated sex differences respective to aging, focusing on cognitive parameters in apoE4 and apoE knockout (ko) mouse models of AD and CVD. Presynaptic density and neurogenesis were investigated immunohistochemically in male and female apoE4, apoE ko, and wild-type mice. Middle-aged female apoE4 mice showed decreased presynaptic density in the inner molecular layer of the dentate gyrus of the hippocampus. Middle-aged female apoE ko mice showed a trend towards increased neurogenesis in the hippocampus compared with wild-type mice. No differences in these parameters could be observed in middle-aged male mice. Specific harmful interactions between apoE4 and estrogen could be responsible for decreased presynaptic density in female apoE4 mice. The trend of increased neurogenesis found in female apoE ko mice supports previous studies suggesting that temporarily increased amount of synaptic contacts and/or neurogenesis is a compensatory mechanism for synaptic failure. To our knowledge, no other studies investigating presynaptic density in aging female apoE4 or apoE ko mice are available. Sex-specific differences between APOE genotypes could account for some sex differences in AD and CVD. A. Rijpma, D. Jansen, I. A. C. Arnoldussen, X. T. Fang, M. Wiesmann, M. P. C. Mutsaers, P. J. Dederen, C. I. F. Janssen, and A. J. Kiliaan Copyright © 2013 A. Rijpma et al. All rights reserved. Neurodegenerative Diseases: Multifactorial Conformational Diseases and Their Therapeutic Interventions Sun, 30 Dec 2012 17:00:57 +0000 http://www.hindawi.com/journals/jnd/2013/563481/ Neurodegenerative diseases are multifactorial debilitating disorders of the nervous system that affect approximately 30 millionindividuals worldwide. Neurodegenerative diseases such as Alzheimer’s, Parkinson’s, Huntington’s, and amyotrophic lateral sclerosis diseases are the consequence of misfolding and dysfunctional trafficking of proteins. Beside that, mitochondrial dysfunction, oxidative stress, and/or environmental factors strongly associated with age have also been implicated in causing neurodegeneration. After years of intensive research, considerable evidence has accumulated that demonstrates an important role of these factors in the etiology of common neurodegenerative diseases. Despite the extensive efforts that have attempted to define the molecular mechanisms underlying neurodegeneration, many aspects of these pathologies remain elusive. However, in order to explore the therapeutic interventions directed towards treatment of neurodegenerative diseases, neuroscientists are now fully exploiting the data obtained from studies of these basic mechanisms that have gone awry. The novelty of these mechanisms represents a challenge to the identification of viable drug targets and biomarkers for early diagnosis of the diseases. In this paper, we are reviewing various aspects associated with the disease and the recent trends that may have an application for the treatment of the neurodegenerative disorders. Saba Sheikh, Safia, Ejazul Haque, and Snober S. Mir Copyright © 2013 Saba Sheikh et al. All rights reserved. The MFN2 V705I Variant Is Not a Disease-Causing Mutation: A Segregation Analysis in a CMT2 Family Wed, 28 Nov 2012 15:48:20 +0000 http://www.hindawi.com/journals/jnd/2013/495873/ Charcot-Marie-Tooth (CMT) disease is a clinically and genetically heterogeneous group of disorders affecting both motor and sensory neurons in the peripheral nervous system. Mutations in the MFN2 gene cause an axonal form of CMT, CMT2A. The V705I variant in MFN2 has been previously reported as a disease-causing mutation in families with CMT2. We identified an affected index patient from an Australian multigenerational family with the V705I variant. Segregation analysis showed that the V705I variant did not segregate with the disease phenotype and was present in control individuals with an allele frequency of 4.4%. We, therefore, propose that the V705I variant is a polymorphism and not a disease-causing mutation as previously reported. Obaid M. Albulym, Danqing Zhu, Stephen Reddel, Marina Kennerson, and Garth Nicholson Copyright © 2013 Obaid M. Albulym et al. All rights reserved. Evaluative Conditioning with Facial Stimuli in Dementia Patients Tue, 04 Sep 2012 08:30:50 +0000 http://www.hindawi.com/journals/jnd/2013/854643/ We present results of a study investigating evaluative learning in dementia patients with a classic evaluative conditioning paradigm. Picture pairs of three unfamiliar faces with liked, disliked, or neutral faces, that were rated prior to the presentation, were presented 10 times each to a group of dementia patients (N = 15) and healthy controls (N = 14) in random order. Valence ratings of all faces were assessed before and after presentation. In contrast to controls, dementia patients changed their valence ratings of unfamiliar faces according to their pairing with either a liked or disliked face, although they were not able to explicitly assign the picture pairs after the presentation. Our finding suggests preserved evaluative conditioning in dementia patients. However, the result has to be considered preliminary, as it is unclear which factors prevented the predicted rating changes in the expected direction in the control group. Andreas Blessing, Jacqueline Zöllig, Roland Weierstall, Gerhard Dammann, and Mike Martin Copyright © 2013 Andreas Blessing et al. All rights reserved. Oxidative Stress and Its Clinical Applications in Dementia Thu, 30 Aug 2012 09:05:04 +0000 http://www.hindawi.com/journals/jnd/2013/319898/ Dementia is a complex disorder that mostly affects the elderly and represents a significant and growing public health burden in the world. Alzheimer’s disease (AD)- associated dementia and dementia with Lewy bodies (DLB) are the most common forms of dementia, in which oxidative stress is significantly involved. Oxidative stress mechanisms may have clinical applications, that is, providing information for potential biomarkers. Thus brain-rich peptides with an antioxidant property, such as CART (cocaine- and amphetamine-regulated transcript), may be promising new markers. This paper summarizes the progress in research regarding oxidative stress in dementia with a focus on potential biomarkers in the cerebrospinal fluid (CSF) in the main forms of dementia. Other central and peripheral biomarkers, especially those considered oxidative stress related, are also discussed. This paper aims to provide information to improve current understanding of the pathogenesis and progression of dementia. It also offers insight into the differential diagnosis of AD and DLB. Peizhong Mao Copyright © 2013 Peizhong Mao. All rights reserved.