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Chao Dong, Ji-Chun Zhang, Wei Yao, Qian Ren, Min Ma, Chun Yang, Shigeyuki Chaki, Kenji Hashimoto
BACKGROUND: Similar to the N-methyl-D-aspartate (NMDA) receptor antagonist ketamine, the metabotropic glutamate 2/3 (mGlu2/3) receptor antagonist, MGS0039 shows antidepressant effects. However, there are no reports comparing these two compounds in the social defeat stress model of depression. METHODS: We examined the effects of MGS0039 (1 mg/kg) and ketamine (10 mg/kg) on depression-like behavior in susceptible mice, after repeated social defeat stress. Protein levels of brain-derived neurotrophic factor (BDNF), TrkB, phospho-TrkB (p-TrkB), α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor (GluA1) and postsynaptic density protein 95 (PSD-95), and dendritic spine density in selected brain regions were measured...
October 7, 2016: International Journal of Neuropsychopharmacology
Petros Petrikis, Vassiliki A Boumba, Alexandros T Tzallas, Paraskevi V Voulgari, Dimitra T Archimandriti, Petros Skapinakis, Venetsanos Mavreas
Insulin-like growth factor 1 (IGF-1) plays an important role in neurogenesis and synaptogenesis and may be implicated in schizophrenia, although data so far have been inconclusive. The aim of our study was to compare levels of IGF-1 in drug-naïve patients with a first episode of schizophrenia and related disorders with matched healthy controls. Forty drug naïve first-episode patients with schizophrenia and related disorders and forty healthy subjects matched for age, gender, body mass index (BMI) and smoking status were enrolled in the study...
September 28, 2016: Psychiatry Research
Mathieu Fonteneau, Dominique Filliol, Patrick Anglard, Katia Befort, Pascal Romieu, Jean Zwiller
DNA methylation is a major epigenetic process which regulates the accessibility of genes to the transcriptional machinery. In the present study, we investigated whether modifying the global DNA methylation pattern in the brain would alter cocaine intake by rats, using the cocaine self-administration test. The data indicate that treatment of rats with the DNA methyltransferase inhibitors 5-aza-2'-deoxycytidine and zebularine actually enhanced the reinforcing properties of cocaine. To get some insights about the underlying neurobiological mechanisms, a genome-wide methylation analysis was undertaken in the prefrontal cortex of rats self-administering cocaine and treated or not with 5-aza-2'-deoxycytidine...
October 20, 2016: Genes, Brain, and Behavior
Ji-Won Lee, Bill X Huang, HeungSun Kwon, Md Abdur Rashid, Giorgi Kharebava, Abhishek Desai, Samarjit Patnaik, Juan Marugan, Hee-Yong Kim
Docosahexaenoic acid (DHA, 22:6n-3) is an omega-3 fatty acid essential for proper brain development. N-docosahexaenoylethanolamine (synaptamide), an endogenous metabolite of DHA, potently promotes neurogenesis, neuritogenesis and synaptogenesis; however, the underlying molecular mechanism is not known. Here, we demonstrate orphan G-protein coupled receptor 110 (GPR110, ADGRF1) as the synaptamide receptor, mediating synaptamide-induced bioactivity in a cAMP-dependent manner. Mass spectrometry-based proteomic characterization and cellular fluorescence tracing with chemical analogues of synaptamide reveal specific binding of GPR110 to synaptamide, which triggers cAMP production with low nM potency...
October 19, 2016: Nature Communications
Yan Xu, Christopher C Quinn
Axonal branch formation and synaptogenesis are sequential events that are required for the establishment of neuronal connectivity. However, little is known about how the transition between these two events is regulated. Here, we report that the lin-4 microRNA can regulate the transition between branch formation and synaptogenesis in the PLM axon of C. elegans. The PLM axon grows a collateral branch during the early L1 stage and undergoes synaptogenesis during the late L1 stage. Loss of the lin-4 microRNA disrupts synaptogenesis during the late L1 stage, suggesting that lin-4 promotes synaptogenesis...
October 13, 2016: Developmental Biology
A S Parent, A Pinson, N Woods, C Chatzi, C E Vaaga, A Bensen, A Gérard, J P Thome, J P Bourguignon, G L Westbrook
Neurogenesis in the dentate gyrus is sensitive to endogenous and exogenous factors that influence hippocampal function. Ongoing neurogenesis and the integration of these new neurons throughout life thus may provide a sensitive indicator of environmental stress. We examined the effects of Aroclor 1254 (A1254), a mixture of polychlorinated biphenyls (PCBs), on the development and function of newly-generated dentate granule cells. Early exposure to A1254 has been associated with learning impairment in children, suggesting potential impact on the development of hippocampus and/or cortical circuits...
October 14, 2016: European Journal of Neuroscience
Edward C Lauterbach
Dextromethorphan (DM) may have ketamine-like rapid-acting, treatment-resistant, and conventional antidepressant effects.(1,2) This reports our initial experience with DM in unipolar Major Depressive Disorder (MDD). A patient with treatment-resistant MDD (failing adequate trials of citalopram and vortioxetine) with loss of antidepressant response (to fluoxetine and bupropion) twice experienced a rapid-acting antidepressant effect within 48 hours of DM administration and lasting 7 days, sustained up to 20 days with daily administration, then gradually developing labile loss of antidepressant response over the ensuing 7 days...
August 15, 2016: Psychopharmacology Bulletin
Byunghyuk Kim, Bangxia Suo, Scott W Emmons
We compare whole-animal RNA-seq transcriptomes for C. elegans males and hermaphrodites from the late L3 larval stage to young adulthood. During this interval, male sexual structures develop, including extensive neurogenesis and synaptogenesis that nearly doubles the size of the nervous system. Previous genome-wide expression studies in C. elegans have usually focused on only one sex-the hermaphrodite-and there are a relatively large number of genes that remain without meaningful annotation. In the present study, differential expression analysis of the RNA-seq data revealed 1,751 genes expressed at a higher level in the male...
October 11, 2016: Cell Reports
Marco Sassoè-Pognetto, Annarita Patrizi
Since the groundbreaking work of Ramon y Cajal, the cerebellar Purkinje cell has always represented an ideal model for studying the organization, development and function of synaptic circuits. Purkinje cells receive distinct types of glutamatergic and GABAergic synapses, each characterized by exquisite sub-cellular and molecular specificity. The formation and refinement of these connections results from a temporally-regulated sequence of events that involves molecular interactions between distinct sets of secreted and surface proteins, as well as activity-dependent competition between converging inputs...
October 6, 2016: Brain Research Bulletin
Vivian Y Poon, Minxia Gu, Fang Ji, Antonius M VanDongen, Marc Fivaz
BACKGROUND: MicroRNAs (miRNAs) are short non-coding RNAs that are emerging as important post-transcriptional regulators of neuronal and synaptic development. The precise impact of miRNAs on presynaptic function and neurotransmission remains, however, poorly understood. RESULTS: Here, we identify miR-27b-an abundant neuronal miRNA implicated in neurological disorders-as a global regulator of the presynaptic transcriptome. miR-27b influences the expression of three quarters of genes associated with presynaptic function in cortical neurons...
October 4, 2016: BMC Genomics
Antonella Tramutola, Andrea Arena, Chiara Cini, D Allan Butterfield, Eugenio Barone
Clinical studies suggest a link between peripheral insulin resistance and cognitive dysfunction. Post-mortem analyses of Alzheimer disease (AD) subjects revealed insulin resistance in the brain, suggesting a role of this condition in cognitive deficits observed in AD. In this review, we focus on the glucagon-like peptide-1 (GLP-1) signaling pathway, whose role in the brain is collecting increasing attention because of its association with insulin signaling activation. Areas covered: The role of GLP-1-mediated effects in the brain and how they are affected along the progression of AD pathology is discussed...
October 7, 2016: Expert Review of Neurotherapeutics
Yi-Sian Lin, Han-Ying Wang, De-Fong Huang, Pei-Fen Hsieh, Meng-Ying Lin, Chih-Hsuan Chou, I-Ju Wu, Guo-Jen Huang, Susan Shur-Fen Gau, Hsien-Sung Huang
Dysfunction of RBFOX3 has been identified in neurodevelopmental disorders such as autism spectrum disorder, cognitive impairments and epilepsy and a causal relationship with these diseases has been previously demonstrated with Rbfox3 homozygous knockout mice. Despite the importance of RBFOX3 during neurodevelopment, the function of RBFOX3 regarding neurogenesis and synaptogenesis remains unclear. To address this critical question, we profiled the developmental expression pattern of Rbfox3 in the brain of wild-type mice and analyzed brain volume, disease-relevant behaviors, neurogenesis, synaptic plasticity, and synaptogenesis in Rbfox3 homozygous knockout mice and their corresponding wild-type counterparts...
2016: PloS One
Yusuke Naito, Alfred Kihoon Lee, Hideto Takahashi
Tropomyosin-receptor-kinase (Trk) receptors have been extensively studied for their roles in kinase-dependent signaling cascades in nervous system development. Synapse organization is coordinated by trans-synaptic interactions of various cell adhesion proteins, a representative example of which is the neurexin-neuroligin complex. Recently, a novel role for TrkC as a synapse organizing protein has been established. Post-synaptic TrkC binds to pre-synaptic type-IIa receptor-type protein tyrosine phosphatase sigma (PTPσ)...
September 30, 2016: Neuroscience Research
Grace M McPhee, Luke A Downey, Anthony Noble, Con Stough
As the elderly population grows the impact of age associated cognitive decline as well as neurodegenerative diseases such as Alzheimer's disease and dementia will increase. Ageing is associated with consistent impairments in cognitive processes (e.g., processing speed, memory, executive function and learning) important for work, well-being, life satisfaction and overall participation in society. Recently, there has been increased effort to conduct research examining methods to improve cognitive function in older citizens...
October 2016: Medical Hypotheses
A-Ram Lee, Kwang Woo Ko, Hojae Lee, Yi-Seul Yoon, Mi-Ryoung Song, Chul-Seung Park
UNLABELLED: During brain development, dynamic changes in neuronal membranes perform critical roles in neuronal morphogenesis and migration to create functional neural circuits. Among the proteins that induce membrane dynamics, cell adhesion molecules are important in neuronal membrane plasticity. Here, we report that V-set and transmembrane domain-containing protein 5 (Vstm5), a cell-adhesion-like molecule belonging to the Ig superfamily, was found in mouse brain. Knock-down of Vstm5 in cultured hippocampal neurons markedly reduced the complexity of dendritic structures, as well as the number of dendritic filopodia...
September 28, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Yulan Xu, Yadan Xue, Lijun Kang
There are three types of glial cells in Caenorhabditis elegans (C. elegans for short): sheath glia, socket glia and glutamate receptor glia. They are mainly located in four sensory organs including the amphid, the cephalic organ, the outer labial sensilla and the inner labial sensilla. C. elegans glial cells play key roles in dendrite extension, neurite guidance and extension, and are essential for synaptogenesis and maintain the normal morphology and the function of sensory nerve endings as well. A recent study shown that some nematode neurons are derived from the glial cells...
May 25, 2016: Zhejiang da Xue Xue Bao. Yi Xue Ban, Journal of Zhejiang University. Medical Sciences
Bi-Qin Lai, Ming-Tian Che, Bao-Ling Du, Xiang Zeng, Yuan-Huan Ma, Bo Feng, Xue-Chen Qiu, Ke Zhang, Shu Liu, Hui-Yong Shen, Jin-Lang Wu, Eng-Ang Ling, Yuan-Shan Zeng
Severe spinal cord injury (SCI) causes loss of neural connectivity and permanent functional deficits. Re-establishment of new neuronal relay circuits after SCI is therefore of paramount importance. The present study tested our hypothesis if co-culture of neurotrophin-3 (NT-3) gene-modified Schwann cells (SCs, NT-3-SCs) and TrkC (NT-3 receptor) gene-modified neural stem cells (NSCs, TrkC-NSCs) in a gelatin sponge scaffold could construct a tissue engineering neural network for re-establishing an anatomical neuronal relay after rat spinal cord transection...
December 2016: Biomaterials
Inseyah Bagasrawala, Fani Memi, Nevena V Radonjić, Nada Zecevic
N-methyl d-aspartate receptors (NMDARs), a subtype of glutamate receptor, have important functional roles in cellular activity and neuronal development. They are well-studied in rodent and adult human brains, but limited information is available about their distribution in the human fetal cerebral cortex. Here we show that 3 NMDAR subunits, NR1, NR2A, and NR2B, are expressed in the human cerebral cortex during the second trimester of gestation, a period of intense neurogenesis and synaptogenesis. With increasing fetal age, expression of the NMDAR-encoding genes Grin1 (NR1) and Grin2a (NR2A) increased while Grin2b (NR2B) expression decreased...
September 24, 2016: Cerebral Cortex
Yue Zhu, Xiuzhu Duan, Xiaoxuan Cheng, Xiaonan Cheng, Xu Li, Liu Zhang, Pei Liu, Su Shulan, Jin-Ao Duan, Tina Ting-Xia Dong, Karl Wah-Keung Tsim, Fei Huang
BACKGROUND: Kai-xin-san (KXS), composed of Ginseng Radix et Rhizoma, Polygalae Radix, Acori Tatarinowii Rhizoma and Poria, is a famous Chinese medicinal formula applied for treating stress-related psychiatric disease with the symptoms such as depression, forgetfulness and dizziness. Dependent on the symptom differentiation of patients, the composition ratio of KXS was varied and one ratio of 3:2:2:3 was widely applied. However, its molecular mechanism has seldom been investigated. PURPOSE: We aimed to reveal the action mechanism of KXS on anti-depression on synaptic protein regulation in both in vivo and in vitro models...
September 19, 2016: Journal of Ethnopharmacology
X U Yulan, Xue Yadan, Kang Lijun
There are three types of glial cells in Caenorhabditis elegans (C. elegans for short): sheath glia, socket glia and glutamate receptor glia. They are mainly located in four sensory organs including the amphid, the cephalic organ, the outer labial sensilla and the inner labial sensilla. C. elegans glial cells play key roles in dendrite extension, neurite guidance and extension, and are essential for synaptogenesis and maintain the normal morphology and the function of sensory nerve endings as well. A recent study shown that some nematode neurons are derived from the glial cells...
May 25, 2016: Zhejiang da Xue Xue Bao. Yi Xue Ban, Journal of Zhejiang University. Medical Sciences
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