Neural Plasticity The latest articles from Hindawi © 2017 , Hindawi Limited . All rights reserved. Maturation, Refinement, and Serotonergic Modulation of Cerebellar Cortical Circuits in Normal Development and in Murine Models of Autism Tue, 15 Aug 2017 00:00:00 +0000 The formation of the complex cerebellar cortical circuits follows different phases, with initial synaptogenesis and subsequent processes of refinement guided by a variety of mechanisms. The regularity of the cellular and synaptic organization of the cerebellar cortex allowed detailed studies of the structural plasticity mechanisms underlying the formation of new synapses and retraction of redundant ones. For the attainment of the monoinnervation of the Purkinje cell by a single climbing fiber, several signals are involved, including electrical activity, contact signals, homosynaptic and heterosynaptic interaction, calcium transients, postsynaptic receptors, and transduction pathways. An important role in this developmental program is played by serotonergic projections that, acting on temporally and spatially regulated postsynaptic receptors, induce and modulate the phases of synaptic formation and maturation. In the adult cerebellar cortex, many developmental mechanisms persist but play different roles, such as supporting synaptic plasticity during learning and formation of cerebellar memory traces. A dysfunction at any stage of this process can lead to disorders of cerebellar origin, which include autism spectrum disorders but are not limited to motor deficits. Recent evidence in animal models links impairment of Purkinje cell function with autism-like symptoms including sociability deficits, stereotyped movements, and interspecific communication by vocalization. Eriola Hoxha, Pellegrino Lippiello, Bibiana Scelfo, Filippo Tempia, Mirella Ghirardi, and Maria Concetta Miniaci Copyright © 2017 Eriola Hoxha et al. All rights reserved. AAV-KLF7 Promotes Descending Propriospinal Neuron Axonal Plasticity after Spinal Cord Injury Sun, 13 Aug 2017 00:00:00 +0000 DPSN axons mediate and maintain a variety of normal spinal functions. Unsurprisingly, DPSN tracts have been shown to mediate functional recovery following SCI. KLF7 could contribute to CST axon plasticity after spinal cord injury. In the present study, we assessed whether KLF7 could effectively promote DPSN axon regeneration and synapse formation following SCI. An AAV-KLF7 construct was used to overexpress KLF7. In vitro, KLF7 and target proteins were successfully elevated and axonal outgrowth was enhanced. In vivo, young adult C57BL/6 mice received a T10 contusion followed by an AAV-KLF7 injection at the T7–9 levels above the lesion. Five weeks later, overexpression of KLF7 was expressed in DPSN. KLF7 and KLF7 target genes (NGF, TrkA, GAP43, and P0) were detectably increased in the injured spinal cord. Myelin sparring at the lesion site, DPSN axonal regeneration and synapse formation, muscle weight, motor endplate morphology, and functional parameters were all additionally improved by KLF7 treatment. Our findings suggest that KLF7 promotes DPSN axonal plasticity and the formation of synapses with motor neurons at the caudal spinal cord, leading to improved functional recovery and further supporting the potential of AAV-KLF7 as a therapeutic agent for spinal cord injury. Wen-Yuan Li, Ying Wang, Feng-Guo Zhai, Ping Sun, Yong-Xia Cheng, Ling-Xiao Deng, and Zhen-Yu Wang Copyright © 2017 Wen-Yuan Li et al. All rights reserved. Brain-Derived Neurotrophic Factor, Depression, and Physical Activity: Making the Neuroplastic Connection Tue, 08 Aug 2017 07:51:32 +0000 Brain-derived neurotrophic factor (BDNF) is a neurotrophin that is vital to the survival, growth, and maintenance of neurons in key brain circuits involved in emotional and cognitive function. Convergent evidence indicates that neuroplastic mechanisms involving BDNF are deleteriously altered in major depressive disorder (MDD) and animal models of stress. Herein, clinical and preclinical evidence provided that stress-induced depressive pathology contributes to altered BDNF level and function in persons with MDD and, thereby, disruptions in neuroplasticity at the regional and circuit level. Conversely, effective therapeutics that mitigate depressive-related symptoms (e.g., antidepressants and physical activity) optimize BDNF in key brain regions, promote neuronal health and recovery of function in MDD-related circuits, and enhance pharmacotherapeutic response. A greater knowledge of the interrelationship between BDNF, depression, therapeutic mechanisms of action, and neuroplasticity is important as it necessarily precedes the derivation and deployment of more efficacious treatments. Cristy Phillips Copyright © 2017 Cristy Phillips. All rights reserved. The Effect of Glucocorticoid and Glucocorticoid Receptor Interactions on Brain, Spinal Cord, and Glial Cell Plasticity Tue, 08 Aug 2017 00:00:00 +0000 Stress, injury, and disease trigger glucocorticoid (GC) elevation. Elevated GCs bind to the ubiquitously expressed glucocorticoid receptor (GR). While GRs are in every cell in the nervous system, the expression level varies, suggesting that diverse cell types react differently to GR activation. Stress/GCs induce structural plasticity in neurons, Schwann cells, microglia, oligodendrocytes, and astrocytes as well as affect neurotransmission by changing the release and reuptake of glutamate. While general nervous system plasticity is essential for adaptation and learning and memory, stress-induced plasticity is often maladaptive and contributes to neuropsychiatric disorders and neuropathic pain. In this brief review, we describe the evidence that stress/GCs activate GR to promote cell type-specific changes in cellular plasticity throughout the nervous system. Kathryn M. Madalena and Jessica K. Lerch Copyright © 2017 Kathryn M. Madalena and Jessica K. Lerch. All rights reserved. Modulation of Central Synapses by Astrocyte-Released ATP and Postsynaptic P2X Receptors Sun, 06 Aug 2017 00:00:00 +0000 Communication between neuronal and glial cells is important for neural plasticity. P2X receptors are ATP-gated cation channels widely expressed in the brain where they mediate action of extracellular ATP released by neurons and/or glia. Recent data show that postsynaptic P2X receptors underlie slow neuromodulatory actions rather than fast synaptic transmission at brain synapses. Here, we review these findings with a particular focus on the release of ATP by astrocytes and the diversity of postsynaptic P2X-mediated modulation of synaptic strength and plasticity in the CNS. Eric Boué-Grabot and Yuriy Pankratov Copyright © 2017 Eric Boué-Grabot and Yuriy Pankratov. All rights reserved. White Matter Hyperintensity Load Modulates Brain Morphometry and Brain Connectivity in Healthy Adults: A Neuroplastic Mechanism? Thu, 03 Aug 2017 04:31:37 +0000 White matter hyperintensities (WMHs) are acquired lesions that accumulate and disrupt neuron-to-neuron connectivity. We tested the associations between WMH load and (1) regional grey matter volumes and (2) functional connectivity of resting-state networks, in a sample of 51 healthy adults. Specifically, we focused on the positive associations (more damage, more volume/connectivity) to investigate a potential route of adaptive plasticity. WMHs were quantified with an automated procedure. Voxel-based morphometry was carried out to model grey matter. An independent component analysis was run to extract the anterior and posterior default-mode network, the salience network, the left and right frontoparietal networks, and the visual network. Each model was corrected for age, global levels of atrophy, and indices of brain and cognitive reserve. Positive associations were found with morphometry and functional connectivity of the anterior default-mode network and salience network. Within the anterior default-mode network, an association was found in the left mediotemporal-limbic complex. Within the salience network, an association was found in the right parietal cortex. The findings support the suggestion that, even in the absence of overt disease, the brain actuates a compensatory (neuroplastic) response to the accumulation of WMH, leading to increases in regional grey matter and modified functional connectivity. Matteo De Marco, Riccardo Manca, Micaela Mitolo, and Annalena Venneri Copyright © 2017 Matteo De Marco et al. All rights reserved. The Temporal Pattern of a Lesion Modulates the Functional Network Topology of Remote Brain Regions Thu, 03 Aug 2017 04:06:52 +0000 Focal brain lesions can alter the morphology and function of remote brain areas. When the damage is inflicted more slowly, the functional compensation by and structural reshaping of these areas seem to be more effective. It remains unclear, however, whether the momentum of lesion development also modulates the functional network topology of the remote brain areas. In this study, we compared resting-state functional connectivity data of patients with a slowly growing low-grade glioma (LGG) with that of patients with a faster-growing high-grade glioma (HGG). Using graph theory, we examined whether the tumour growth velocity modulated the functional network topology of remote areas, more specifically of the hemisphere contralateral to the lesion. We observed that the contralesional network topology characteristics differed between patient groups. Based only on the connectivity of the hemisphere contralateral to the lesion, patients could be classified in the correct tumour-grade group with 70% accuracy. Additionally, LGG patients showed smaller contralesional intramodular connectivity, smaller contralesional ratio between intra- and intermodular connectivity, and larger contralesional intermodular connectivity than HGG patients. These results suggest that, in the hemisphere contralateral to the lesion, there is a lower capacity for local, specialized information processing coupled to a higher capacity for distributed information processing in LGG patients. These results underline the utility of a network perspective in evaluating effects of focal brain injury. W. De Baene, G. J. M. Rutten, and M. M. Sitskoorn Copyright © 2017 W. De Baene et al. All rights reserved. A Hypothalamic Leptin-Glutamate Interaction in the Regulation of Sympathetic Nerve Activity Thu, 03 Aug 2017 00:00:00 +0000 Accumulated evidence indicates that obesity-induced type 2 diabetes (T2D) is associated with enhanced sympathetic activation. The present study was conducted to investigate the role for leptin-glutamate signaling within the hypothalamus in regulating sympathetic nerve activity. In anesthetized rats, microinjections of leptin (5 ng ~ 100 ng) into the arcuate nucleus (ARCN) and paraventricular nucleus (PVN) induced increases in renal sympathetic nerve activity (RSNA), blood pressure (BP), and heart rate (HR). Prior microinjections of NMDA receptor antagonist AP5 (16 pmol) into the ARCN or PVN reduced leptin-induced increases in RSNA, BP, and HR in both ARCN and PVN. Knockdown of a leptin receptor with siRNA inhibited NMDA-induced increases in RSNA, BP, and HR in the ARCN but not in the PVN. Confocal calcium imaging in the neuronal NG108 and astrocytic C6 cells demonstrated that preincubation with leptin induced an increase in intracellular calcium green fluorescence when the cells were challenged with glutamate. In high-fat diet and low-dose streptozotocin-induced T2D rats, we found that leptin receptor and NMDA NR1 receptor expressions in the ARCN and PVN were significantly increased. In conclusion, these studies provide evidence that within the hypothalamic nuclei, leptin-glutamate signaling regulates the sympathetic activation. This may contribute to the sympathoexcitation commonly observed in obesity-related T2D. Hong Zheng, Xuefei Liu, Yulong Li, and Kaushik P. Patel Copyright © 2017 Hong Zheng et al. All rights reserved. Emotion Processing by ERP Combined with Development and Plasticity Mon, 31 Jul 2017 00:00:00 +0000 Emotions important for survival and social interaction have received wide and deep investigations. The application of the fMRI technique into emotion processing has obtained overwhelming achievements with respect to the localization of emotion processes. The ERP method, which possesses highly temporal resolution compared to fMRI, can be employed to investigate the time course of emotion processing. The emotional modulation of the ERP component has been verified across numerous researches. Emotions, described as dynamically developing along with the growing age, have the possibility to be enhanced through learning (or training) or to be damaged due to disturbances in growth, which is underlain by the neural plasticity of emotion-relevant nervous systems. And mood disorders with typical symptoms of emotion discordance probably have been caused by the dysfunctional neural plasticity. Rui Ding, Ping Li, Wei Wang, and Wenbo Luo Copyright © 2017 Rui Ding et al. All rights reserved. Exercise Promotes Neuroplasticity in Both Healthy and Depressed Brains: An fMRI Pilot Study Sun, 30 Jul 2017 00:00:00 +0000 Memory impairments are a frequently reported cognitive symptom in people suffering from major depressive disorder (MDD) and often persist despite antidepressant therapy. Neuroimaging studies have identified abnormal hippocampal activity during memory processes in MDD. Exercise as an ad-on treatment for MDD is a promising therapeutic strategy shown to improve mood, cognitive function, and neural structure and function. To advance our understanding of how exercise impacts neural function in MDD, we must also understand how exercise impacts healthy individuals without MDD. This pilot study used a subsequent memory paradigm to investigate the effects of an eight-week exercise intervention on hippocampal function in low-active healthy () and low-active MDD () individuals. Results showed a marked improvement in depression scores for the MDD group () and no change in memory performance for either group (). Functional imaging results showed a marginally significant decrease in hippocampal activity in both groups following the exercise intervention. Our whole brain analysis collapsed across groups revealed a similar deactivation pattern across several memory-associated regions. These results suggest that exercise may enhance neural efficiency in low-fit individuals while still resulting in a substantially greater mood effect for those suffering from MDD. This trial is registered with clinical NCT03191994. Joanne Gourgouvelis, Paul Yielder, and Bernadette Murphy Copyright © 2017 Joanne Gourgouvelis et al. All rights reserved. Learning “How to Learn”: Super Declarative Motor Learning Is Impaired in Parkinson’s Disease Sun, 30 Jul 2017 00:00:00 +0000 Learning new information is crucial in daily activities and occurs continuously during a subject’s lifetime. Retention of learned material is required for later recall and reuse, although learning capacity is limited and interference between consecutively learned information may occur. Learning processes are impaired in Parkinson’s disease (PD); however, little is known about the processes related to retention and interference. The aim of this study is to investigate the retention and anterograde interference using a declarative sequence learning task in drug-naive patients in the disease’s early stages. Eleven patients with PD and eleven age-matched controls learned a visuomotor sequence, SEQ1, during Day1; the following day, retention of SEQ1 was assessed and, immediately after, a new sequence of comparable complexity, SEQ2, was learned. The comparison of the learning rates of SEQ1 on Day1 and SEQ2 on Day2 assessed the anterograde interference of SEQ1 on SEQ2. We found that SEQ1 performance improved in both patients and controls on Day2. Surprisingly, controls learned SEQ2 better than SEQ1, suggesting the absence of anterograde interference and the occurrence of learning optimization, a process that we defined as “learning how to learn.” Patients with PD lacked such improvement, suggesting defective performance optimization processes. Lucio Marinelli, Carlo Trompetto, Stefania Canneva, Laura Mori, Flavio Nobili, Francesco Fattapposta, Antonio Currà, Giovanni Abbruzzese, and Maria Felice Ghilardi Copyright © 2017 Lucio Marinelli et al. 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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.