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https://www.readbyqxmd.com/read/29230399/role-of-protein-kinase-c-in-bipolar-disorder-a-review-of-the-current-literature
#1
REVIEW
Ashwini Saxena, Giselli Scaini, Daniela V Bavaresco, Camila Leite, Samira S Valvassoria, André F Carvalho, João Quevedo
Bipolar disorder (BD) is a major health problem. It causes significant morbidity and imposes a burden on the society. Available treatments help a substantial proportion of patients but are not beneficial for an estimated 40-50%. Thus, there is a great need to further our understanding the pathophysiology of BD to identify new therapeutic avenues. The preponderance of evidence pointed towards a role of protein kinase C (PKC) in BD. We reviewed the literature pertinent to the role of PKC in BD. We present recent advances from preclinical and clinical studies that further support the role of PKC...
November 2017: Molecular Neuropsychiatry
https://www.readbyqxmd.com/read/29230184/neuroligin-2-r215h-mutant-mice-manifest-anxiety-increased-prepulse-inhibition-and-impaired-spatial-learning-and-memory
#2
Chia-Hsiang Chen, Pin-Wei Lee, Hsiao-Mei Liao, Pi-Kai Chang
Neuroligin 2 (NLGN2) is a postsynaptic adhesion protein that plays an essential role in synaptogenesis and function of inhibitory neuron. We previously identified a missense mutation R215H of the NLGN2 in a patient with schizophrenia. This missense mutation was shown to be pathogenic in several cell-based assays. The objective of this study was to better understand the behavioral consequences of this mutation in vivo. We generated a line of transgenic mice carrying this mutation using a recombinant-based method...
2017: Frontiers in Psychiatry
https://www.readbyqxmd.com/read/29227343/golgi-fragmentation-induced-by-overactivated-cyclin-dependent-kinase-5-is-associated-with-isoflurane-induced-neurotoxicity
#3
Fang-Fang Miao, Cui-Cui Kong, Yan Wu, Long Fan, Tian-Long Wang
Overactivated cyclin-dependent kinase 5 (Cdk5) induces Golgi fragmentation, which interrupts the processing and trafficking of secretory cargo and subsequently synaptic plasticity and synaptogenesis, and even leads to neuronal cell death. Cdk5 overactivation and subsequent Golgi fragmentation are involved in many neurodegenerative diseases. However, whether isoflurane-induced neurotoxicity is relevant to aberrant Cdk5 activation and subsequent Golgi fragmentation remains unknown. In the present study, we explored the underlying molecular mechanisms of isoflurane-induced neurotoxicity in primary cultured hippocampal neurons...
December 8, 2017: Neuroreport
https://www.readbyqxmd.com/read/29226467/axon-guidance-pathways-and-the-control-of-gene-expression
#4
REVIEW
Samantha A Russell, Greg J Bashaw
Axons need to be properly guided to their targets to form synaptic connections, and this requires interactions between highly conserved extracellular and transmembrane ligands and their cell surface receptors. The majority of studies on axon guidance signaling pathways have focused on the role of these pathways in rearranging the local cytoskeleton and plasma membrane in growth cones and axons. However, a smaller body of work has demonstrated that axon guidance signaling pathways also control gene expression via local translation and transcription...
December 11, 2017: Developmental Dynamics: An Official Publication of the American Association of Anatomists
https://www.readbyqxmd.com/read/29225544/novel-targets-for-developing-antiseizure-and-potentially-antiepileptogenic-drugs
#5
Dipan C Patel, Karen S Wilcox, Cameron S Metcalf
Epilepsy is a chronic neurological disorder caused by abnormal changes in the functions of neuronal circuits and manifested by seizures. It affects patients of all age, substantially worsens the quality of life for the patients as well as their families, and imposes a huge economic burden on the healthcare system. Historically, efforts for discovering and developing antiseizure therapies have been focused on modulating the functions of receptors, transporters, and enzymes expressed by neurons. These drug development efforts have paid off, as we have over 25 antiseizure drugs available in the clinic...
September 2017: Epilepsy Currents
https://www.readbyqxmd.com/read/29225336/psychiatric-polygenic-risk-associates-with-cortical-morphology-and-functional-organization-in-aging
#6
Annie Lee, Mojun Shen, Anqi Qiu
Common brain abnormalities in cortical morphology and functional organization are observed in psychiatric disorders and aging, reflecting shared genetic influences. This preliminary study aimed to examine the contribution of a polygenetic risk for psychiatric disorders (PRScross) to aging brain and to identify molecular mechanisms through the use of multimodal brain images, genotypes, and transcriptome data. We showed age-related cortical thinning in bilateral inferior frontal cortex (IFC) and superior temporal gyrus and alterations in the functional connectivity between bilateral IFC and between right IFC and right inferior parietal lobe as a function of PRScross...
December 11, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/29221166/high-salt-induced-hypertension-leads-to-cognitive-defect
#7
Cui-Ping Guo, Zhen Wei, Fang Huang, Min Qin, Xing Li, Yu-Man Wang, Qun Wang, Jian-Zhi Wang, Rong Liu, Bin Zhang, Hong-Lian Li, Xiao-Chuan Wang
Although increasing evidences suggest a relationship between hypertension and brain function for years, it is still unclear whether hypertension constitutes a risk factor for cognitive decline and its underlying mechanism. In the present study, an experimental animal model of hypertension simply by feeding rats with high salt diet was employed. We found that long-term high salt intake caused a marked increase of systolic blood pressure linked to a declined regional cerebral blood flow. Fear conditioning and morris water maze behavioral test revealed that high salt diet induced hippocampal dependent spatial reference memory deficits, while a decreased synaptogenesis without neuronal loss in hippocampus was observed in high salt treated rats...
November 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29218848/shank1-is-differentially-expressed-during-development-in-ca1-hippocampal-neurons-and-astrocytes
#8
Sean M Collins, Amogh P Belagodu, Samantha L Reed, Roberto Galvez
Recent studies have strongly suggested a role for the synaptic scaffolding protein SHANK1 in normal synaptic structure and signaling. Global SHANK1 knockout (SHANK1-/-) mice demonstrate reduced dendritic spine density, an immature dendritic spine phenotype and impairments in various cognitive tasks. SHANK1 overexpression is associated with increased dendritic spine size and impairments in fear conditioning. These studies suggest proper regulation of SHANK1 is crucial for appropriate synaptic structure and cognition...
December 8, 2017: Developmental Neurobiology
https://www.readbyqxmd.com/read/29212022/alpha2delta-1-in-sf1-neurons-of-the-ventromedial-hypothalamus-is-an-essential-regulator-of-glucose-and-lipid-homeostasis
#9
Jennifer A Felsted, Cheng-Hao Chien, Dongqing Wang, Micaella Panessiti, Dominique Ameroso, Andrew Greenberg, Guoping Feng, Dong Kong, Maribel Rios
The central mechanisms controlling glucose and lipid homeostasis are inadequately understood. We show that α2δ-1 is an essential regulator of glucose and lipid balance, acting in steroidogenic factor-1 (SF1) neurons of the ventromedial hypothalamus (VMH). These effects are body weight independent and involve regulation of SF1+ neuronal activity and sympathetic output to metabolic tissues. Accordingly, mice with α2δ-1 deletion in SF1 neurons exhibit glucose intolerance, altered lipolysis, and decreased cholesterol content in adipose tissue despite normal energy balance regulation...
December 5, 2017: Cell Reports
https://www.readbyqxmd.com/read/29209878/cell-type-specific-spatiotemporal-expression-of-creatine-biosynthetic-enzyme-s-adenosylmethionine-guanidinoacetate-n-methyltransferase-in-developing-mouse-brain
#10
Masanori Tachikawa, Masahiko Watanabe, Masahiro Fukaya, Kazuhisa Sakai, Tetsuya Terasaki, Ken-Ichi Hosoya
Creatine is synthesized by S-adenosylmethionine:guanidinoacetate N-methyltransferase (GAMT), and the creatine/phosphocreatine shuttle system mediated by creatine kinase (CK) is essential for storage and regeneration of high-energy phosphates in cells. Although the importance of this system in brain development is evidenced by the hereditary nature of creatine deficiency syndrome, the spatiotemporal cellular expression patterns of GAMT in developing brain remain unknown. Here we show that two waves of high GAMT expression occur in developing mouse brain...
December 5, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/29209173/fundamental-elements-in-autism-from-neurogenesis-and-neurite-growth-to-synaptic-plasticity
#11
REVIEW
James Gilbert, Heng-Ye Man
Autism spectrum disorder (ASD) is a set of neurodevelopmental disorders with a high prevalence and impact on society. ASDs are characterized by deficits in both social behavior and cognitive function. There is a strong genetic basis underlying ASDs that is highly heterogeneous; however, multiple studies have highlighted the involvement of key processes, including neurogenesis, neurite growth, synaptogenesis and synaptic plasticity in the pathophysiology of neurodevelopmental disorders. In this review article, we focus on the major genes and signaling pathways implicated in ASD and discuss the cellular, molecular and functional studies that have shed light on common dysregulated pathways using in vitro, in vivo and human evidence...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/29207144/dner-modulates-the-length-polarity-and-synaptogenesis-of-spiral-ganglion-neurons-via-the-notch-signaling-pathway
#12
Jintao Du, Xianren Wang, Xiaobo Zhang, Xuemei Zhang, Hongyan Jiang
The Delta/Notch‑like epidermal growth factor‑related receptor (DNER) serves an important role in the developing central nervous system. However, the actions of DNER in the development of the spiral ganglion in the inner ear have yet to be elucidated. Wild‑type C57BL/6 mice were housed and time‑mated for use in the present study. Primary neuronal cultures were prepared using spiral ganglion progenitors isolated from the modiolus of postnatal day 1 (P1) mice. DNER recombinant lentiviral vectors were constructed and transfected into the cultured primary neurons...
November 20, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29204194/synaptogenesis-in-the-cerebellum-of-offspring-born-to-diabetic-mothers
#13
REVIEW
Javad Hami, Saeed Vafaei-Nezhad, Akram Sadeghi, Kazem Ghaemi, Mohammad-Mahdi Hasanzadeh Taheri, Mohammad Fereidouni, Ghasem Ivar, Mehran Hosseini
There is increasing evidence that maternal diabetes mellitus during the pregnancy is associated with a higher risk of neurodevelopmental and neurofunctional anomalies including motor dysfunctions, learning deficits, and behavioral problems in offspring. The cerebellum is a part of the brain that has long been recognized as a center of movement balance and motor coordination. Moreover, recent studies in humans and animals have also implicated the cerebellum in cognitive processing, sensory discrimination, attention, and learning and memory...
July 2017: Journal of Pediatric Neurosciences
https://www.readbyqxmd.com/read/29203796/aerobic-exercise-and-a-bdnf-mimetic-therapy-rescue-learning-and-memory-in-a-mouse-model-of-down-syndrome
#14
Martina Parrini, Diego Ghezzi, Gabriele Deidda, Lucian Medrihan, Enrico Castroflorio, Micol Alberti, Pietro Baldelli, Laura Cancedda, Andrea Contestabile
Down syndrome (DS) is caused by the triplication of human chromosome 21 and represents the most frequent genetic cause of intellectual disability. The trisomic Ts65Dn mouse model of DS shows synaptic deficits and reproduces the essential cognitive disabilities of the human syndrome. Aerobic exercise improved various neurophysiological dysfunctions in Ts65Dn mice, including hippocampal synaptic deficits, by promoting synaptogenesis and neurotransmission at glutamatergic terminals. Most importantly, the same intervention also prompted the recovery of hippocampal adult neurogenesis and synaptic plasticity and restored cognitive performance in trisomic mice...
December 4, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29203228/mild-fluid-percussion-injury-induces-diffuse-axonal-damage-and-reactive-synaptic-plasticity-in-the-mouse-olfactory-bulb
#15
Melissa A Powell, Raiford T Black, Terry L Smith, Thomas M Reeves, Linda L Phillips
Despite the regenerative capacity of the olfactory bulb (OB), head trauma causes olfactory disturbances in up to 30% of patients. While models of olfactory nerve transection, olfactory receptor neuron (ORN) ablation, or direct OB impact have been used to examine OB recovery, these models are severe and not ideal for study of OB synaptic repair. We posited that a mild fluid percussion brain injury (mFPI), delivered over mid-dorsal cortex, would produce diffuse OB deafferentation without confounding pathology...
December 1, 2017: Neuroscience
https://www.readbyqxmd.com/read/29199528/gene-networks-associated-with-non-syndromic-intellectual-disability
#16
Soohyun Lee, Stephen Rudd, Jacob Gratten, Peter M Visscher, Johannes B Prins, Paul A Dawson
Non-syndromic intellectual disability (NS-ID) is a genetically heterogeneous disorder, with more than 200 candidate genes to date. Despite the increasing number of novel mutations detected, a relatively low number of recurrently mutated genes have been identified, highlighting the complex genetic architecture of the disorder. A systematic search of PubMed and Medline identified 245 genes harbouring non-synonymous variants, insertions or deletions, which were identified as candidate NS-ID genes from case reports or from linkage or pedigree analyses...
December 4, 2017: Journal of Neurogenetics
https://www.readbyqxmd.com/read/29197626/microglia-key-players-in-neurodevelopment-and-neuronal-plasticity
#17
Luba Sominsky, Simone De Luca, Sarah J Spencer
Microglia are the primary innate immune cells in the CNS. Since their initial discovery and characterization, decades of research have revealed their unique roles not only in maintaining immune homeostasis, but also being indispensable to brain development and cognitive function. As such, microglia drive synaptogenesis, synaptic pruning, neurogenesis and neuronal activity. Microglia-specific mutations are implicated in several neurodevelopmental disorders, and dysregulation of microglial function is strongly linked to several pathologies, including cognitive decline and Alzheimer's disease...
December 1, 2017: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/29196321/mt3-mmp-promotes-excitatory-synapse-formation-by-promoting-nogo-66-receptor-ectodomain-shedding
#18
Ricardo L Sanz, Gino B Ferraro, Johannes Kacervosky, Charleen Salesse, Elizabeth Gowing, Luyang Hua, Isabel Rambaldi, Francois Beaubien, Kenn Holmbeck, J F Cloutier, Martin Lévesque, Keith Murai, Alyson E Fournier
Cell surface molecules are dynamically regulated at the synapse to assemble and disassemble adhesive contacts that are important for synaptogenesis and for tuning synaptic transmission. Metalloproteinases dynamically regulate cellular behaviors through the processing of cell surface molecules. In the present study, we evaluated the role of membrane-type metalloproteinases (MT-MMPs) in excitatory synaptogenesis. We find that MT3-MMP and MT5-MMP are broadly expressed in the mouse cerebral cortex and that MT3-MMP loss-of-function interferes with excitatory synapse development in dissociated cortical neurons and in vivo We identify Nogo-66 receptor (NgR1) as an MT3-MMP substrate that is required for MT3-MMP-dependent synapse formation...
December 1, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29187810/conditional-loss-of-hoxa5-function-early-after-birth-impacts-on-expression-of-genes-with-synaptic-function
#19
Benoit Lizen, Charlotte Moens, Jinane Mouheiche, Thomas Sacré, Marie-Thérèse Ahn, Lucie Jeannotte, Ahmad Salti, Françoise Gofflot
Hoxa5 is a member of the Hox gene family that plays critical roles in successive steps of the central nervous system formation during embryonic and fetal development. In the mouse, Hoxa5 was recently shown to be expressed in the medulla oblongata and the pons from fetal stages to adulthood. In these territories, Hoxa5 transcripts are enriched in many precerebellar neurons and several nuclei involved in autonomic functions, while the HOXA5 protein is detected mainly in glutamatergic and GABAergic neurons. However, whether HOXA5 is functionally required in these neurons after birth remains unknown...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/29182533/early-gabapentin-treatment-during-the-latency-period-increases-convulsive-threshold-reduces-microglial-activation-and-macrophage-infiltration-in-the-lithium-pilocarpine-model-of-epilepsy
#20
Alicia Rossi, Veronica Murta, Jerónimo Auzmendi, Alberto Javier Ramos
The lithium-pilocarpine model of epilepsy reproduces several features of temporal lobe epilepsy in humans, including the chronological timeline of an initial latency period followed by the development of spontaneous seizures. Epilepsy therapies in humans are implemented, as a rule, after the onset of the spontaneous seizures. We here studied the potential effect on epileptogenesis of starting an early treatment during the latency period, in order to prevent the development of spontaneous seizures. Adult male Wistar rats were treated with 3 mEq/kg LiCl, and 20 h later 30 mg/kg pilocarpine...
November 28, 2017: Pharmaceuticals
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