Neural Plasticity https://www.hindawi.com The latest articles from Hindawi © 2017 , Hindawi Limited . All rights reserved. Genesis and Maintenance of Attentional Biases: The Role of the Locus Coeruleus-Noradrenaline System Thu, 20 Jul 2017 00:00:00 +0000 http://www.hindawi.com/journals/np/2017/6817349/ Emotionally arousing events are typically better remembered than mundane ones, in part because emotionally relevant aspects of our environment are prioritized in attention. Such biased attentional tuning is itself the result of associative processes through which we learn affective and motivational relevance of cues. We propose that the locus coeruleus-noradrenaline (LC-NA) system plays an important role in the genesis of attentional biases through associative learning processes as well as their maintenance. We further propose that individual differences in and disruptions of the LC-NA system underlie the development of maladaptive biases linked to psychopathology. We provide support for the proposed role of the LC-NA system by first reviewing work on attentional biases in development and its link to psychopathology in relation to alterations and individual differences in NA availability. We focus on pharmacological manipulations to demonstrate the effect of a disrupted system as well as the ADRA2b polymorphism as a tool to investigate naturally occurring differences in NA availability. We next review associative learning processes that—modulated by the LC-NA system—result in such implicit attentional biases. Further, we demonstrate how NA may influence aversive and appetitive conditioning linked to anxiety disorders as well as addiction and depression. Mana R. Ehlers and Rebecca M. Todd Copyright © 2017 Mana R. Ehlers and Rebecca M. Todd. All rights reserved. Developmental Changes in Sleep Oscillations during Early Childhood Sun, 16 Jul 2017 00:00:00 +0000 http://www.hindawi.com/journals/np/2017/6160959/ Although quantitative analysis of the sleep electroencephalogram (EEG) has uncovered important aspects of brain activity during sleep in adolescents and adults, similar findings from preschool-age children remain scarce. This study utilized our time-frequency method to examine sleep oscillations as characteristic features of human sleep EEG. Data were collected from a longitudinal sample of young children (; 3 males) at ages 2, 3, and 5 years. Following sleep stage scoring, we detected and characterized oscillatory events across age and examined how their features corresponded to spectral changes in the sleep EEG. Results indicated a developmental decrease in the incidence of delta and theta oscillations. Spindle oscillations, however, were almost absent at 2 years but pronounced at 5 years. All oscillatory event changes were stronger during light sleep than slow-wave sleep. Large interindividual differences in sleep oscillations and their characteristics (e.g., “ultrafast” spindle-like oscillations, theta oscillation incidence/frequency) also existed. Changes in delta and spindle oscillations across early childhood may indicate early maturation of the thalamocortical system. Our analytic approach holds promise for revealing novel types of sleep oscillatory events that are specific to periods of rapid normal development across the lifespan and during other times of aberrant changes in neurobehavioral function. Eckehard Olbrich, Thomas Rusterholz, Monique K. LeBourgeois, and Peter Achermann Copyright © 2017 Eckehard Olbrich et al. All rights reserved. Stress Induced Neuroplasticity and Mental Disorders Thu, 13 Jul 2017 00:00:00 +0000 http://www.hindawi.com/journals/np/2017/9634501/ Fushun Wang, Fang Pan, Lee A. Shapiro, and Jason H. Huang Copyright © 2017 Fushun Wang et al. All rights reserved. Study on Lesion Assessment of Cerebello-Thalamo-Cortical Network in Wilson’s Disease with Diffusion Tensor Imaging Tue, 11 Jul 2017 05:37:16 +0000 http://www.hindawi.com/journals/np/2017/7323121/ Wilson’s disease (WD) is a genetic disorder of copper metabolism with pathological copper accumulation in the brain and any other tissues. This article aimed to assess lesions in cerebello-thalamo-cortical network with an advanced technique of diffusion tensor imaging (DTI) in WD. 35 WD patients and 30 age- and sex-matched healthy volunteers were recruited to accept diffusion-weighted images with 15 gradient vectors and conventional magnetic resonance imaging (MRI). The DTI parameters, including fractional anisotropy (FA) and mean diffusion (MD), were calculated by diffusion kurtosis estimator software. After registration, patient groups with FA mappings and MD mappings and normal groups were compared with 3dttest and receiver-operating characteristic (ROC) curve analysis, corrected with FDR simulations (, , cluster size = 326). We found that the degree of FA increased in the bilateral head of the caudate nucleus (HCN), lenticular nucleus (LN), ventral thalamus, substantia nigra (SN), red nucleus (RN), right dentate nucleus (DN), and decreased in the mediodorsal thalamus and extensive white matter. The value of MD increased in HCN, LN, SN, RN, and extensive white matter. The technique of DTI provides higher sensitivity and specificity than conventional MRI to detect Wilson’s disease. Besides, lesions in the basal ganglia, thalamus, and cerebellum might disconnect the basal ganglia-thalamo-cortical circuits or dentato-rubro-thalamic (DRT) track and disrupt cerebello-thalamo-cortical network finally, which may cause clinical extrapyramidal symptoms. Anqin Wang, Hongli Wu, Chunsheng Xu, Lanfeng Tang, Jaeyoun Lee, Min Wang, Man Jiang, Chuanfu Li, Qi Lu, and Chunyun Zhang Copyright © 2017 Anqin Wang et al. All rights reserved. Enkephalins: Endogenous Analgesics with an Emerging Role in Stress Resilience Tue, 11 Jul 2017 00:00:00 +0000 http://www.hindawi.com/journals/np/2017/1546125/ Psychological stress is a state of mental or emotional strain or tension that results from adverse or demanding circumstances. Chronic stress is well known to induce anxiety disorders and major depression; it is also considered a risk factor for Alzheimer’s disease. Stress resilience is a positive outcome that is associated with preserved cognition and healthy aging. Resilience presents psychological and biological characteristics intrinsic to an individual conferring protection against the development of psychopathologies in the face of adversity. How can we promote or improve resilience to chronic stress? Numerous studies have proposed mechanisms that could trigger this desirable process. The roles of enkephalin transmission in the control of pain, physiological functions, like respiration, and affective disorders have been studied for more than 30 years. However, their role in the resilience to chronic stress has received much less attention. This review presents the evidence for an emerging involvement of enkephalin signaling through its two associated opioid receptors, μ opioid peptide receptor and δ opioid peptide receptor, in the natural adaptation to stressful lifestyles. Mathilde S. Henry, Louis Gendron, Marie-Eve Tremblay, and Guy Drolet Copyright © 2017 Mathilde S. Henry et al. All rights reserved. Anodal Transcranial Direct Current Stimulation Provokes Neuroplasticity in Repetitive Mild Traumatic Brain Injury in Rats Sun, 09 Jul 2017 00:00:00 +0000 http://www.hindawi.com/journals/np/2017/1372946/ Repetitive mild traumatic brain injury (rmTBI) provokes behavioral and cognitive changes. But the study about electrophysiologic findings and managements of rmTBI is limited. In this study, we investigate the effects of anodal transcranial direct current stimulation (tDCS) on rmTBI. Thirty-one Sprague Dawley rats were divided into the following groups: sham, rmTBI, and rmTBI treated by tDCS. Animals received closed head mTBI three consecutive times a day. Anodal tDCS was applied to the left motor cortex. We evaluated the motor-evoked potential (MEP) and the somatosensory-evoked potential (SEP). T2-weighted magnetic resonance imaging was performed 12 days after rmTBI. After rmTBI, the latency of MEP was prolonged and the amplitude in the right hind limb was reduced in the rmTBI group. The latency of SEP was delayed and the amplitude was decreased after rmTBI in the rmTBI group. In the tDCS group, the amplitude in both hind limbs was increased after tDCS in comparison with the values before rmTBI. Anodal tDCS after rmTBI seems to be a useful tool for promoting transient motor recovery through increasing the synchronicity of cortical firing, and it induces early recovery of consciousness. It can contribute to management of concussion in humans if further study is performed. Ho Jeong Kim and Soo Jeong Han Copyright © 2017 Ho Jeong Kim and Soo Jeong Han. All rights reserved. Potential Roles of Exosomal MicroRNAs as Diagnostic Biomarkers and Therapeutic Application in Alzheimer’s Disease Sun, 09 Jul 2017 00:00:00 +0000 http://www.hindawi.com/journals/np/2017/7027380/ Exosomes are bilipid layer-enclosed vesicles derived from endosomes and are released from neural cells. They contain a diversity of proteins, mRNAs, and microRNAs (miRNAs) that are delivered to neighboring cells and/or are transported to distant sites. miRNAs released from exosomes appear to be associated with multiple neurodegenerative conditions linking to Alzheimer’s disease (AD) which is marked by hyperphosphorylated tau proteins and accumulation of Aβ plaques. Exciting findings reveal that miRNAs released from exosomes modulate the expression and function of amyloid precursor proteins (APP) and tau proteins. These open up the possibility that dysfunctional exosomal miRNAs may influence AD progression. In addition, it has been confirmed that the interaction between miRNAs released by exosomes and Toll-like receptors (TLR) initiates inflammation. In exosome support-deprived neurons, exosomal miRNAs may regulate neuroplasticity to relieve neurological damage. In this review, we summarize the literature on the function of exosomal miRNAs in AD pathology, the potential of these miRNAs as diagnostic biomarkers in AD, and the use of exosomes in the delivery of miRNAs which may lead to major advances in the field of macromolecular drug delivery. Jian-jiao Chen, Bin Zhao, Jie Zhao, and Shao Li Copyright © 2017 Jian-jiao Chen et al. All rights reserved. Human APP Gene Expression Alters Active Zone Distribution and Spontaneous Neurotransmitter Release at the Drosophila Larval Neuromuscular Junction Sun, 09 Jul 2017 00:00:00 +0000 http://www.hindawi.com/journals/np/2017/9202584/ This study provides further insight into the molecular mechanisms that control neurotransmitter release. Experiments were performed on larval neuromuscular junctions of transgenic Drosophila melanogaster lines with different levels of human amyloid precursor protein (APP) production. To express human genes in motor neurons of Drosophila, the UAS-GAL4 system was used. Human APP gene expression increased the number of synaptic boutons per neuromuscular junction. The total number of active zones, detected by Bruchpilot protein puncta distribution, remained unchanged; however, the average number of active zones per bouton decreased. These disturbances were accompanied by a decrease in frequency of miniature excitatory junction potentials without alteration in random nature of spontaneous quantal release. Similar structural and functional changes were observed with co-overexpression of human APP and β-secretase genes. In Drosophila line with expression of human amyloid-β42 peptide itself, parameters analyzed did not differ from controls, suggesting the specificity of APP effects. These results confirm the involvement of APP in synaptogenesis and provide evidence to suggest that human APP overexpression specifically disturbs the structural and functional organization of active zone and results in altered Bruchpilot distribution and lowered probability of spontaneous neurotransmitter release. Ekaterina A. Saburova, Alexander N. Vasiliev, Violetta V. Kravtsova, Elena V. Ryabova, Andrey L. Zefirov, Olga I. Bolshakova, Svetlana V. Sarantseva, and Igor I. Krivoi Copyright © 2017 Ekaterina A. Saburova et al. All rights reserved. Endophilin2 Interacts with GluA1 to Mediate AMPA Receptor Endocytosis Induced by Oligomeric Amyloid-β Wed, 05 Jul 2017 03:43:03 +0000 http://www.hindawi.com/journals/np/2017/8197085/ Amyloid-β (Aβ) plays an important role in Alzheimer’s disease (AD), as oligomeric Aβ induces loss of postsynaptic AMPA receptors (AMPARs) leading to cognitive deficits. The loss of postsynaptic AMPARs is mediated through the clathrin-dependent endocytosis pathway, in which endophilin2 is one of the important regulatory proteins. Endophilin2, which is enriched in both the pre- and postsynaptic membrane, has previously been reported to be important for recycling of synaptic vesicles at the presynaptic membrane. However, the role of endophilin2 in oligomeric Aβ-induced postsynaptic AMPAR endocytosis is not well understood. In this study, we show that endophilin2 does not affect constitutive AMPAR endocytosis. Endophilin2 knockdown, but not overexpression, resisted oligomeric Aβ-induced AMPAR dysfunction. Moreover, endophilin2 colocalized and interacted with GluA1, a subunit of AMPAR, to regulate oligomeric Aβ-induced AMPAR endocytosis. Thus, we have determined a role of endophilin2 in oligomeric Aβ-induced postsynaptic AMPAR dysfunction, indicating possible directions for preventing the loss of AMPARs in cognitive impairment and providing evidence for the clinical treatment of AD. Jifeng Zhang, Yichen Yin, Zhisheng Ji, Zhenbin Cai, Bo Zhao, Jiong Li, Minghui Tan, and Guoqing Guo Copyright © 2017 Jifeng Zhang et al. All rights reserved. Tail Nerve Electrical Stimulation and Electro-Acupuncture Can Protect Spinal Motor Neurons and Alleviate Muscle Atrophy after Spinal Cord Transection in Rats Wed, 28 Jun 2017 00:00:00 +0000 http://www.hindawi.com/journals/np/2017/7351238/ Spinal cord injury (SCI) often results in death of spinal neurons and atrophy of muscles which they govern. Thus, following SCI, reorganizing the lumbar spinal sensorimotor pathways is crucial to alleviate muscle atrophy. Tail nerve electrical stimulation (TANES) has been shown to activate the central pattern generator (CPG) and improve the locomotion recovery of spinal contused rats. Electroacupuncture (EA) is a traditional Chinese medical practice which has been proven to have a neural protective effect. Here, we examined the effects of TANES and EA on lumbar motor neurons and hindlimb muscle in spinal transected rats, respectively. From the third day postsurgery, rats in the TANES group were treated 5 times a week and those in the EA group were treated once every other day. Four weeks later, both TANES and EA showed a significant impact in promoting survival of lumbar motor neurons and expression of choline acetyltransferase (ChAT) and ameliorating atrophy of hindlimb muscle after SCI. Meanwhile, the expression of neurotrophin-3 (NT-3) in the same spinal cord segment was significantly increased. These findings suggest that TANES and EA can augment the expression of NT-3 in the lumbar spinal cord that appears to protect the motor neurons as well as alleviate muscle atrophy. Yu-Ting Zhang, Hui Jin, Jun-Hua Wang, Lan-Yu Wen, Yang Yang, Jing-Wen Ruan, Shu-Xin Zhang, Eng-Ang Ling, Ying Ding, and Yuan-Shan Zeng Copyright © 2017 Yu-Ting Zhang et al. All rights reserved. A Combined Water Extract of Frankincense and Myrrh Alleviates Neuropathic Pain in Mice via Modulation of TRPV1 Tue, 27 Jun 2017 00:00:00 +0000 http://www.hindawi.com/journals/np/2017/3710821/ Frankincense and myrrh are widely used in clinics as a pair of herbs to obtain a synergistic effect for relieving pain. To illuminate the analgesia mechanism of frankincense and myrrh, we assessed its effect in a neuropathic pain mouse model. Transient receptor potential vanilloid 1 (TRPV1) plays a crucial role in neuropathic pain and influences the plasticity of neuronal connectivity. We hypothesized that the water extraction of frankincense and myrrh (WFM) exerted its analgesia effect by modulating the neuronal function of TRPV1. In our study, WFM was verified by UHPLC-TQ/MS assay. In vivo study showed that nociceptive response in mouse by heat and capsaicin induced were relieved by WFM treatment. Furthermore, thermal hypersensitivity and mechanical allodynia were also alleviated by WFM treatment in a chronic constriction injury (CCI) mouse model. CCI resulted in increased TRPV1 expression at both the mRNA and protein levels in predominantly small-to-medium neurons. However, after WFM treatment, TRPV1 expression was reverted in real-time PCR, Western blot, and immunofluorescence experiments. Calcium response to capsaicin was also decreased in cultured DRG neurons from CCI model mouse after WFM treatment. In conclusion, WFM alleviated CCI-induced mechanical allodynia and thermal hypersensitivity via modulating TRPV1. Danyou Hu, Changming Wang, Fengxian Li, Shulan Su, Niuniu Yang, Yan Yang, Chan Zhu, Hao Shi, Lei Yu, Xiao Geng, Leying Gu, Xiaolin Yuan, Zhongli Wang, Guang Yu, and Zongxiang Tang Copyright © 2017 Danyou Hu et al. All rights reserved. Effect of Hypoxic Injury in Mood Disorder Thu, 22 Jun 2017 00:00:00 +0000 http://www.hindawi.com/journals/np/2017/6986983/ Hypoxemia is a common complication of the diseases associated with the central nervous system, and neurons are highly sensitive to the availability of oxygen. Neuroplasticity is an important property of the neural system controlling breathing, memory, and cognitive ability. However, the underlying mechanism has not yet been clearly elucidated. In recent years, several pieces of evidence have highlighted the effect of hypoxic injury on neuronal plasticity in the pathogenesis and treatment of mood disorder. Therefore, the present study reviewed the relevant articles regarding hypoxic injury and neuronal plasticity and discussed the pathological changes and physiological functions of neurons in hypoxemia in order to provide a translational perspective to the relevance of hypoxic injury and mood disorder. Fenglian Zhao, Junling Yang, and Ranji Cui Copyright © 2017 Fenglian Zhao et al. All rights reserved. Improving and Predicting Outcomes of Traumatic Brain Injury: Neuroplasticity, Imaging Modalities, and Perspective Therapy Thu, 22 Jun 2017 00:00:00 +0000 http://www.hindawi.com/journals/np/2017/4752546/ Chih-Lung Lin, Aaron S. Dumont, John H. Zhang, Mario Zuccarello, and Cheng-Sheng Chen Copyright © 2017 Chih-Lung Lin et al. All rights reserved. Assessment of Emotional Expressions after Full-Face Transplantation Wed, 21 Jun 2017 00:00:00 +0000 http://www.hindawi.com/journals/np/2017/8789724/ We assessed clinical features as well as sensory and motor recoveries in 3 full-face transplantation patients. A frequency analysis was performed on facial surface electromyography data collected during 6 basic emotional expressions and 4 primary facial movements. Motor progress was assessed using the wavelet packet method by comparison against the mean results obtained from 10 healthy subjects. Analyses were conducted on 1 patient at approximately 1 year after face transplantation and at 2 years after transplantation in the remaining 2 patients. Motor recovery was observed following sensory recovery in all 3 patients; however, the 3 cases had different backgrounds and exhibited different degrees and rates of sensory and motor improvements after transplant. Wavelet packet energy was detected in all patients during emotional expressions and primary movements; however, there were fewer active channels during expressions in transplant patients compared to healthy individuals, and patterns of wavelet packet energy were different for each patient. Finally, high-frequency components were typically detected in patients during emotional expressions, but fewer channels demonstrated these high-frequency components in patients compared to healthy individuals. Our data suggest that the posttransplantation recovery of emotional facial expression requires neural plasticity. Çağdaş Topçu, Hilmi Uysal, Ömer Özkan, Özlenen Özkan, Övünç Polat, Merve Bedeloğlu, Arzu Akgül, Ela Naz Döğer, Refik Sever, Nur Ebru Barçın, Kadriye Tombak, and Ömer Halil Çolak Copyright © 2017 Çağdaş Topçu et al. All rights reserved. The Link between Depression and Chronic Pain: Neural Mechanisms in the Brain Mon, 19 Jun 2017 07:46:07 +0000 http://www.hindawi.com/journals/np/2017/9724371/ Chronic pain, as a stress state, is one of the critical factors for determining depression, and their coexistence tends to further aggravate the severity of both disorders. Unfortunately, their association remains unclear, which creates a bottleneck problem for managing chronic pain-induced depression. In recent years, studies have found considerable overlaps between pain- and depression-induced neuroplasticity changes and neurobiological mechanism changes. Such overlaps are vital to facilitating the occurrence and development of chronic pain and chronic pain-induced depression. In this review, we summarized the role of neuroplasticity in the occurrence and development of the two disorders in question and explored individualized application strategies of analgesic drugs and antidepressants that have different pharmacological effects in the treatment of chronic pain-induced depression. Therefore, this review may provide new insights into the understanding of association between chronic pain and depression. Jiyao Sheng, Shui Liu, Yicun Wang, Ranji Cui, and Xuewen Zhang Copyright © 2017 Jiyao Sheng et al. All rights reserved. Emulation with Organic Memristive Devices of Impairment of LTP Mechanism in Neurodegenerative Disease Pathology Mon, 19 Jun 2017 06:45:24 +0000 http://www.hindawi.com/journals/np/2017/6090312/ We explore and demonstrate the extension of the synapse-mimicking properties of memristive devices to a dysfunctional synapse as it occurs in the Alzheimer’s disease (AD) pathology. The ability of memristive devices to reproduce synapse properties such as LTP, LTD, and STDP has been already widely demonstrated, and moreover, they were used for developing artificial neuron networks (perceptrons) able to simulate the information transmission in a cell network. However, a major progress would be to extend the common sense of neuromorphic device even to the case of dysfunction of natural synapses. Can memristors efficiently simulate them? We provide here evidences of the ability of emulating the dysfunctional synaptic behavior typical of the AD pathology with organic memristive devices considering the effect of the disease not only on a single synapse but also in the case of a neural network, composed by numerous synapses. Silvia Battistoni, Victor Erokhin, and Salvatore Iannotta Copyright © 2017 Silvia Battistoni et al. All rights reserved. Circadian Rhythms in Fear Conditioning: An Overview of Behavioral, Brain System, and Molecular Interactions Sun, 18 Jun 2017 00:00:00 +0000 http://www.hindawi.com/journals/np/2017/3750307/ The formation of fear memories is a powerful and highly evolutionary conserved mechanism that serves the behavioral adaptation to environmental threats. Accordingly, classical fear conditioning paradigms have been employed to investigate fundamental molecular processes of memory formation. Evidence suggests that a circadian regulation mechanism allows for a timestamping of such fear memories and controlling memory salience during both their acquisition and their modification after retrieval. These mechanisms include an expression of molecular clocks in neurons of the amygdala, hippocampus, and medial prefrontal cortex and their tight interaction with the intracellular signaling pathways that mediate neural plasticity and information storage. The cellular activities are coordinated across different brain regions and neural circuits through the release of glucocorticoids and neuromodulators such as acetylcholine, which integrate circadian and memory-related activation. Disturbance of this interplay by circadian phase shifts or traumatic experience appears to be an important factor in the development of stress-related psychopathology, considering these circadian components are of critical importance for optimizing therapeutic approaches to these disorders. Anne Albrecht and Oliver Stork Copyright © 2017 Anne Albrecht and Oliver Stork. All rights reserved. Erratum to “A Novel Nonsense Mutation of POU4F3 Gene Causes Autosomal Dominant Hearing Loss” Sun, 18 Jun 2017 00:00:00 +0000 http://www.hindawi.com/journals/np/2017/9202847/ Chi Zhang, Mingming Wang, Yun Xiao, Fengguo Zhang, Yicui Zhou, Jianfeng Li, Qingyin Zheng, Xiaohui Bai, and Haibo Wang Copyright © 2017 Chi Zhang et al. All rights reserved. Action Video Game Experience Related to Altered Large-Scale White Matter Networks Thu, 15 Jun 2017 00:00:00 +0000 http://www.hindawi.com/journals/np/2017/7543686/ With action video games (AVGs) becoming increasingly popular worldwide, the cognitive benefits of AVG experience have attracted continuous research attention over the past two decades. Research has repeatedly shown that AVG experience can causally enhance cognitive ability and is related to neural plasticity in gray matter and functional networks in the brain. However, the relation between AVG experience and the plasticity of white matter (WM) network still remains unclear. WM network modulates the distribution of action potentials, coordinating the communication between brain regions and acting as the framework of neural networks. And various types of cognitive deficits are usually accompanied by impairments of WM networks. Thus, understanding this relation is essential in assessing the influence of AVG experience on neural plasticity and using AVG experience as an interventional tool for impairments of WM networks. Using graph theory, this study analyzed WM networks in AVG experts and amateurs. Results showed that AVG experience is related to altered WM networks in prefrontal networks, limbic system, and sensorimotor networks, which are related to cognitive control and sensorimotor functions. These results shed new light on the influence of AVG experience on the plasticity of WM networks and suggested the clinical applicability of AVG experience. Diankun Gong, Weiyi Ma, Jinnan Gong, Hui He, Li Dong, Dan Zhang, Jianfu Li, Cheng Luo, and Dezhong Yao Copyright © 2017 Diankun Gong et al. All rights reserved. Impaired Hippocampal Glutamate and Glutamine Metabolism in the db/db Mouse Model of Type 2 Diabetes Mellitus Wed, 14 Jun 2017 05:28:02 +0000 http://www.hindawi.com/journals/np/2017/2107084/ Type 2 diabetes mellitus (T2DM) is a risk factor for the development of Alzheimer’s disease, and changes in brain energy metabolism have been suggested as a causative mechanism. The aim of this study was to investigate the cerebral metabolism of the important amino acids glutamate and glutamine in the db/db mouse model of T2DM. Glutamate and glutamine are both substrates for mitochondrial oxidation, and oxygen consumption was assessed in isolated brain mitochondria by Seahorse XFe96 analysis. In addition, acutely isolated cerebral cortical and hippocampal slices were incubated with [U-13C]glutamate and [U-13C]glutamine, and tissue extracts were analyzed by gas chromatography-mass spectrometry. The oxygen consumption rate using glutamate and glutamine as substrates was not different in isolated cerebral mitochondria of db/db mice compared to controls. Hippocampal slices of db/db mice exhibited significantly reduced 13C labeling in glutamate, glutamine, GABA, citrate, and aspartate from metabolism of [U-13C]glutamate. Additionally, reduced 13C labeling were observed in GABA, citrate, and aspartate from [U-13C]glutamine metabolism in hippocampal slices of db/db mice when compared to controls. None of these changes were observed in cerebral cortical slices. The results suggest specific hippocampal impairments in glutamate and glutamine metabolism, without affecting mitochondrial oxidation of these substrates, in the db/db mouse. Jens Velde Andersen, Jakob Dahl Nissen, Sofie Kjellerup Christensen, Kia Hjulmand Markussen, and Helle Sønderby Waagepetersen Copyright © 2017 Jens Velde Andersen et al. All rights reserved. Environmental Factors Promoting Neural Plasticity: Insights from Animal and Human Studies Wed, 14 Jun 2017 03:17:00 +0000 http://www.hindawi.com/journals/np/2017/7219461/ We do not all grow older in the same way. Some individuals have a cognitive decline earlier and faster than others who are older in years but cerebrally younger. This is particularly easy to verify in people who have maintained regular physical activity and healthy and cognitively stimulating lifestyle and even in the clinical field. There are patients with advanced neurodegeneration, such as Alzheimer’s disease (AD), that, despite this, have mild cognitive impairment. What determines this interindividual difference? Certainly, it cannot be the result of only genetic factors. We are made in a certain manner and what we do acts on our brain. In fact, our genetic basis can be modulated, modified, and changed by our experiences such as education and life events; daily, by sleep schedules and habits; or also by dietary elements. And this can be seen as true even if our experiences are indirectly driven by our genetic basis. In this paper, we will review some current scientific research on how our experiences are able to modulate the structural organization of the brain and how a healthy lifestyle (regular physical activity, correct sleep hygiene, and healthy diet) appears to positively affect cognitive reserve. Laura Mandolesi, Francesca Gelfo, Laura Serra, Simone Montuori, Arianna Polverino, Giuseppe Curcio, and Giuseppe Sorrentino Copyright © 2017 Laura Mandolesi et al. All rights reserved. Identification of TMPRSS3 as a Significant Contributor to Autosomal Recessive Hearing Loss in the Chinese Population Tue, 13 Jun 2017 00:00:00 +0000 http://www.hindawi.com/journals/np/2017/3192090/ Hereditary hearing loss is characterized by a high degree of genetic heterogeneity. Mutations in the TMPRSS3 (transmembrane protease, serine 3) gene cause prelingual (DFNB10) or postlingual (DFNB8) deafness. In our previous study, three pathogenic mutations in TMPRSS3 were identified in one Chinese family. To evaluate the importance of TMPRSS3 mutations in recessive deafness among the Chinese, we screened 150 autosomal recessive nonsyndromic hearing loss (ARNSHL) families and identified 6 that carried seven causative TMPRSS3 mutations, including five novel mutations (c.809T>A, c.1151T>G, c.1204G>A, c.1244T>C, and c.1250G>A) and two previously reported mutations (c.323-6G>A and c.916G>A). Each of the five novel mutations was classified as severe, by both age of onset and severity of hearing loss. Together with our previous study, six families were found to share one pathogenic mutation (c.916G>A, p.Ala306Thr). To determine whether this mutation arose from a common ancestor, we analyzed six short tandem repeat (STR) markers spanning the TMPRSS3 gene. In four families, we observed linkage disequilibrium between p.Ala306Thr and STR markers. Our results indicate that mutations in TMPRSS3 account for about 4.6% (7/151) of Chinese ARNSHL cases lacking mutations in SLC26A4 or GJB2 and that the recurrent TMPRSS3 mutation p.Ala306Thr is likely to be a founder mutation. Xue Gao, Sha-Sha Huang, Yong-Yi Yuan, Jin-Cao Xu, Ping Gu, Dan Bai, Dong-Yang Kang, Ming-Yu Han, Guo-Jian Wang, Mei-Guang Zhang, Jia Li, and Pu Dai Copyright © 2017 Xue Gao et al. All rights reserved. Lifestyle Modulators of Neuroplasticity: How Physical Activity, Mental Engagement, and Diet Promote Cognitive Health during Aging Mon, 12 Jun 2017 03:42:13 +0000 http://www.hindawi.com/journals/np/2017/3589271/ The number of the elderly across the globe will approximate 2.1 billion by 2050. Juxtaposed against this burgeoning segment of the population is evidence that nonpathological aging is associated with an increased risk for cognitive decline in a variety of domains, changes that can cause mild disability even before the onset of dementia. Given that pharmacological treatments that mitigate dementia are still outstanding, alternative therapeutic options are being investigated increasingly. The results from translational studies have shown that modifiable lifestyle factors—including physical activity, cognitive engagement, and diet—are a key strategy for maintaining brain health during aging. Indeed, a multiplicity of studies has demonstrated relationships between lifestyle factors, brain structure and function, and cognitive function in aging adults. For example, physical activity and diet modulate common neuroplasticity substrates (neurotrophic signaling, neurogenesis, inflammation, stress response, and antioxidant defense) in the brain whereas cognitive engagement enhances brain and cognitive reserve. The aims of this review are to evaluate the relationship between modifiable lifestyle factors, neuroplasticity, and optimal brain health during aging; to identify putative mechanisms that contribute positive brain aging; and to highlight future directions for scientists and clinicians. Undoubtedly, the translation of cutting-edge knowledge derived from the field of cognitive neuroscience will advance our understanding and enhance clinical treatment interventions as we endeavor to promote brain health during aging. Cristy Phillips Copyright © 2017 Cristy Phillips. All rights reserved. The Longevity of Hippocampus-Dependent Memory Is Orchestrated by the Locus Coeruleus-Noradrenergic System Sun, 11 Jun 2017 00:00:00 +0000 http://www.hindawi.com/journals/np/2017/2727602/ The locus coeruleus is connected to the dorsal hippocampus via strong fiber projections. It becomes activated after arousal and novelty, whereupon noradrenaline is released in the hippocampus. Noradrenaline from the locus coeruleus is involved in modulating the encoding, consolidation, retrieval, and reversal of hippocampus-based memory. Memory storage can be modified by the activation of the locus coeruleus and subsequent facilitation of hippocampal long-term plasticity in the forms of long-term depression and long-term potentiation. Recent evidence indicates that noradrenaline and dopamine are coreleased in the hippocampus from locus coeruleus terminals, thus fostering neuromodulation of long-term synaptic plasticity and memory. Noradrenaline is an inductor of epigenetic modifications regulating transcriptional control of synaptic long-term plasticity to gate the endurance of memory storage. In conclusion, locus coeruleus activation primes the persistence of hippocampus-based long-term memory. Niels Hansen Copyright © 2017 Niels Hansen. All rights reserved. Autism-Like Behaviours and Memory Deficits Result from a Western Diet in Mice Thu, 08 Jun 2017 00:00:00 +0000 http://www.hindawi.com/journals/np/2017/9498247/ Nonalcoholic fatty liver disease, induced by a Western diet (WD), evokes central and peripheral inflammation that is accompanied by altered emotionality. These changes can be associated with abnormalities in social behaviour, hippocampus-dependent cognitive functions, and metabolism. Female C57BL/6J mice were fed with a regular chow or with a WD containing 0.2% of cholesterol and 21% of saturated fat for three weeks. WD-treated mice exhibited increased social avoidance, crawl-over and digging behaviours, decreased body-body contacts, and hyperlocomotion. The WD-fed group also displayed deficits in hippocampal-dependent performance such as contextual memory in a fear conditioning and pellet displacement paradigms. A reduction in glucose tolerance and elevated levels of serum cholesterol and leptin were also associated with the WD. The peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PPARGC1a) mRNA, a marker of mitochondrial activity, was decreased in the prefrontal cortex, hippocampus, hypothalamus, and dorsal raphe, suggesting suppressed brain mitochondrial functions, but not in the liver. This is the first report to show that a WD can profoundly suppress social interactions and induce dominant-like behaviours in naïve adult mice. The spectrum of behaviours that were found to be induced are reminiscent of symptoms associated with autism, and, if paralleled in humans, suggest that a WD might exacerbate autism spectrum disorder. Ekaterina Veniaminova, Raymond Cespuglio, Chi Wai Cheung, Alexei Umriukhin, Nataliia Markova, Elena Shevtsova, Klaus-Peter Lesch, Daniel C. Anthony, and Tatyana Strekalova Copyright © 2017 Ekaterina Veniaminova et al. All rights reserved. Abnormal Functional Connectivity of Ventral Anterior Insula in Asthmatic Patients with Depression Wed, 07 Jun 2017 00:00:00 +0000 http://www.hindawi.com/journals/np/2017/7838035/ Objective. To explore the underlying mechanism of depression in asthmatic patients, the ReHo in the insula and its FC was used to probe the differences between depressed asthmatic (DA) and nondepressed asthmatic (NDA) patients. Methods. 18 DA patients, 24 NDA patients, and 60 healthy controls (HCs) received resting-state fMRI scan, severity of depression, and asthma control assessment. Results. DA patients showed increased FC between the left ventral anterior insula (vAI) and the left middle temporal gyrus compared with both NDA and HC groups. In addition, compared with HCs, the DA and NDA patients both exhibited increased FC between the left vAI and the right anterior cingulate cortex (ACC), decreased FC between the left vAI and the bilateral parietal lobe, and increased FC between the right vAI and the left putamen and the right caudate, respectively. Furthermore, the increased FC between the left vAI and the right ACC could differentiate HCs from both DA and NDA patients, and the increased FC between the right vAI and both the left putamen and the right caudate could separate NDA patients from HCs. Conclusions. This study confirmed that abnormal vAI FC may be involved in the neuropathology of depression in asthma. The increased FC between the left vAI and the left MTG could distinguish DA from the NDA and HC groups. Yuqun Zhang, Yuan Yang, Rongrong Bian, Yingying Yin, Zhenghua Hou, Yingying Yue, Zhi Xu, and Yonggui Yuan Copyright © 2017 Yuqun Zhang et al. All rights reserved. Visual Plasticity in Adults Sun, 04 Jun 2017 00:00:00 +0000 http://www.hindawi.com/journals/np/2017/8469580/ Jiawei Zhou, Zili Liu, Simon Clavagnier, Alexandre Reynaud, and Fang Hou Copyright © 2017 Jiawei Zhou et al. All rights reserved. Nicotinamide Administration Improves Remyelination after Stroke Thu, 01 Jun 2017 00:00:00 +0000 http://www.hindawi.com/journals/np/2017/7019803/ Aims. Stroke is a leading cause of morbidity and mortality. This study aimed to determine whether nicotinamide administration could improve remyelination after stroke and reveal the underlying mechanism. Methods. Adult male C57BL/6J mice were intraperitoneally (i.p.) administered with nicotinamide (200 mg/kg, daily) or saline after stroke induced by photothrombotic occlusion of the middle cerebral artery. FK866 (3 mg/kg, daily, bis in die), an inhibitor of NAMPT, and ANA-12 (0.5 mg/kg, daily), an antagonist of tropomyosin-related kinase B (TrkB), were administered intraperitoneally 1 h before nicotinamide administration. Functional recovery, MRI, and histological assessment were performed after stroke at different time points. Results. The nicotinamide-treated mice showed significantly lower infarct area 7 d after stroke induction and significantly higher fractional anisotropy (FA) in the ipsilesional internal capsule (IC) 14 d after stroke induction than the other groups. Higher levels of NAD+, BDNF, and remyelination markers were observed in the nicotinamide-treated group. FK866 administration reduced NAD+ and BDNF levels in the nicotinamide-treated group. ANA-12 administration impaired the recovery from stroke with no effect on NAD+ and BDNF levels. Furthermore, lesser functional deficits were observed in the nicotinamide-treated group than in the control group. Conclusions. Nicotinamide administration improves remyelination after stroke via the NAD+/BDNF/TrkB pathway. Congxiao Wang, Yi Zhang, Jie Ding, Zhen Zhao, Cheng Qian, Ying Luan, and Gao-Jun Teng Copyright © 2017 Congxiao Wang et al. All rights reserved. Inherited Paediatric Motor Neuron Disorders: Beyond Spinal Muscular Atrophy Sun, 28 May 2017 00:00:00 +0000 http://www.hindawi.com/journals/np/2017/6509493/ Paediatric motor neuron diseases encompass a group of neurodegenerative diseases characterised by the onset of muscle weakness and atrophy before the age of 18 years, attributable to motor neuron loss across various neuronal networks in the brain and spinal cord. While the genetic underpinnings are diverse, advances in next generation sequencing have transformed diagnostic paradigms. This has reinforced the clinical phenotyping and molecular genetic expertise required to navigate the complexities of such diagnoses. In turn, improved genetic technology and subsequent gene identification have enabled further insights into the mechanisms of motor neuron degeneration and how these diseases form part of a neurodegenerative disorder spectrum. Common pathophysiologies include abnormalities in axonal architecture and function, RNA processing, and protein quality control. This review incorporates an overview of the clinical manifestations, genetics, and pathophysiology of inherited paediatric motor neuron disorders beyond classic SMN1-related spinal muscular atrophy and describes recent advances in next generation sequencing and its clinical application. Specific disease-modifying treatment is becoming a clinical reality in some disorders of the motor neuron highlighting the importance of a timely and specific diagnosis. Hooi Ling Teoh, Kate Carey, Hugo Sampaio, David Mowat, Tony Roscioli, and Michelle Farrar Copyright © 2017 Hooi Ling Teoh et al. All rights reserved. Sortilin-Related Receptor Expression in Human Neural Stem Cells Derived from Alzheimer’s Disease Patients Carrying the APOE Epsilon 4 Allele Sun, 28 May 2017 00:00:00 +0000 http://www.hindawi.com/journals/np/2017/1892612/ Alzheimer’s disease (AD) is the most common form of dementia in the elderly; important risk factors are old age and inheritance of the apolipoprotein E4 (APOE4) allele. Changes in amyloid precursor protein (APP) binding, trafficking, and sorting may be important AD causative factors. Secretase-mediated APP cleavage produces neurotoxic amyloid-beta (Aβ) peptides, which form lethal deposits in the brain. In vivo and in vitro studies have implicated sortilin-related receptor (SORL1) as an important factor in APP trafficking and processing. Recent in vitro evidence has associated the APOE4 allele and alterations in the SORL1 pathway with AD development and progression. Here, we analyzed SORL1 expression in neural stem cells (NSCs) from AD patients carrying null, one, or two copies of the APOE4 allele. We show reduced SORL1 expression only in NSCs of a patient carrying two copies of APOE4 allele with increased Aβ/SORL1 localization along the degenerated neurites. Interestingly, SORL1 binding to APP was largely compromised; this could be almost completely reversed by γ-secretase (but not β-secretase) inhibitor treatment. These findings may yield new insights into the complex interplay of SORL1 and AD pathology and point to NSCs as a valuable tool to address unsolved AD-related questions in vitro. Alen Zollo, Zoe Allen, Helle F. Rasmussen, Filomena Iannuzzi, Yichen Shi, Agnete Larsen, Thorsten J. Maier, and Carmela Matrone Copyright © 2017 Alen Zollo et al. All rights reserved.