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https://www.readbyqxmd.com/read/29017814/pituitary-adenylate-cyclase-activating-polypeptide-induces-long-term-transcription-dependent-plasticity-and-remodeling-at-autonomic-synapses
#1
Eric R Starr, Joseph F Margiotta
Pituitary adenylate cyclase activating polypeptide (PACAP) is a multifunctional neuropeptide, widely expressed in the nervous system (Vaudry et al., 2009; Starr and Margiotta, 2016). At neuronal synapses where transmission is mediated by nicotinic acetylcholine receptor (nAChRs) transient PACAP exposure increases the frequency and amplitude (FS and AS) of spontaneous excitatory postsynaptic currents (sEPSCs) within minutes. This short-term (ST) plasticity requires high-affinity PACAP receptor (PAC1R) signaling via adenylate cyclase (AC), cyclic AMP (cAMP), Protein kinase A (PKA) and obligatory nAChR-dependent stimulation of nitric oxide (NO) synthesis to retrogradely increase presynaptic ACh release (Pugh et al...
October 7, 2017: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/28981195/nhe5-deficiency-enhances-learning-and-memory-via-upregulating-bdnf-trkb-signaling-in-mice
#2
Xuejiao Chen, Xiyi Wang, Lingyun Tang, Jinjin Wang, Chunling Shen, Jianbing Liu, Shunyuan Lu, Hongxin Zhang, Ying Kuang, Jian Fei, Zhugang Wang
Nhe5, a Na(+) /H(+) exchanger, is predominantly expressed in brain tissue and is proposed to act as a negative regulator of dendritic spine growth. Up to now, its physiological function in vivo remains unclear. Here we show that Nhe5-deficient mice exhibit markedly enhanced learning and memory in Morris water maze, novel object recognition, and passive avoidance task. Meanwhile, the pre- and post-synaptic components, synaptophysin (Syn) and post-synaptic density 95 (PSD95) expression levels were found increased in hippocampal regions lacking of Nhe5, suggesting a possible alterations in neuronal synaptic structure and function in Nhe5(-/-) mice...
October 5, 2017: American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics
https://www.readbyqxmd.com/read/28962170/electro-acupuncture-ameliorates-cognitive-impairment-via-improvement-of-brain-derived-neurotropic-factor-mediated-hippocampal-synaptic-plasticity-in-cerebral-ischemia-reperfusion-injured-rats
#3
Ruhui Lin, Xiaojie Li, Weilin Liu, Wenlie Chen, Kunqiang Yu, Congkuai Zhao, Jia Huang, Shanli Yang, Hongwei Peng, Jing Tao, Lidian Chen
A previous study by our group found that electro-acupuncture (EA) at the Shenting (DU24) and Baihui (DU20) acupoints ameliorates cognitive impairment in rats with cerebral ischemia-reperfusion (I/R) injury. However, the precise mechanism of action has remained largely unknown. The present study investigated whether brain-derived neurotropic factor (BDNF) mediates hippocampal synaptic plasticity as the underlying mechanism. Rats were randomly divided into three groups: The sham operation control (Sham) group, the focal cerebral ischemia-reperfusion (I/R) group, and the I/R with EA treatment (I/R+EA) group...
September 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28924363/thrombospondin-1-gene-deficiency-worsens-the-neurological-outcomes-of-traumatic-brain-injury-in-mice
#4
Chongjie Cheng, Zhanyang Yu, Song Zhao, Zhengbu Liao, Changhong Xing, Yinghua Jiang, Yong-Guang Yang, Michael J Whalen, Eng H Lo, Xiaochuan Sun, Xiaoying Wang
Background: Thrombospondin-1 (TSP-1) is an extracellular matrix protein that plays multiple physiological and pathophysiological roles in the brain. Experimental reports suggest that TSP-1 may have an adverse role in neuronal function recovery under certain injury conditions. However, the roles of TSP-1 in traumatic brain injury (TBI) have not been elucidated. In this study we for the first time investigated the roles of TSP-1 in a controlled cortical impact (CCI) model of TBI in TSP-1 knockout (TSP-1 KO) and wild type (WT) mice...
2017: International Journal of Medical Sciences
https://www.readbyqxmd.com/read/28890050/modulation-of-hippocampal-synapse-maturation-by-activity-regulated-e3-ligase-via-non-canonical-pathway
#5
Pushpa Kumari, Balakumar Srinivasan, Sourav Banerjee
Development of functional synapses is crucial for the transmission and storage of information in the brain. Post establishment of the initial synaptic contact, synapses are stabilized through neuronal activity-induced signals. Emerging studies have implicated ubiquitination; a reversible posttranslational modification, as a key regulatory switch that modulates synapse development through proteasomal degradation. Ubiquitination of proteins is precisely regulated by E3 ligases, a set of enzymes that bind to specific substrates to facilitate the conjugation of monomeric or polymeric ubiquitin...
September 8, 2017: Neuroscience
https://www.readbyqxmd.com/read/28887487/trkb-enhancer-facilitates-functional-recovery-after-traumatic-brain-injury
#6
John Marshall, Joanna Szmydynger-Chodobska, Mengia S Rioult-Pedotti, Kara Lau, Andrea T Chin, Siva K Reddy Kotla, Rakesh Kumar Tiwari, Keykavous Parang, Steven W Threlkeld, Adam Chodobski
Brain-derived neurotrophic factor (BDNF), a key player in regulating synaptic strength and learning, is dysregulated following traumatic brain injury (TBI), suggesting that stimulation of BDNF signaling pathways may facilitate functional recovery. This study investigates whether CN2097, a peptidomimetic ligand which targets the synaptic scaffold protein, postsynaptic density protein 95, to enhance downstream signaling of tropomyosin-related kinase B, a receptor for BDNF, can improve neurological function after TBI...
September 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28880744/the-effects-of-phenylethanoid-glycosides-derived-from-herba-cistanche-on-cognitive-deficits-and-antioxidant-activities-in-male-samp8-mice
#7
Jian-Xin Jia, Xu-Sheng Yan, Zhi-Ping Cai, Wei Song, Dong-Sheng Huo, Bai-Feng Zhang, He Wang, Zhan-Jun Yang
Cognitive deficits are closely associated with hippocampal synaptic changes. Phenylethanoid glycosides (PhG), derived from Herba cistanche, are known to exert protective effects on cognitive deficits in Alzheimer's disease (AD); however, the underlying mechanisms of this herbal extract on cognitive performance remain unclear. The aim of this study was thus to examine the protective mechanism attributed to PhG on cognitive deficits in an AD senescence accelerated mouse prone 8 (SAMP8) model. Cognitive deficit parameters examined included (1) Morris water maze (MWM) assessing cognitive performance and (2) quantification of dendritic spine density in hippocampal CA1 region by Golgi staining, a molecular biomarker of synaptic function...
September 7, 2017: Journal of Toxicology and Environmental Health. Part A
https://www.readbyqxmd.com/read/28866469/l-type-vdccs-participate-in-behavioral-ltp-and-memory-retention
#8
Yuan-Yuan Han, Xiao-Dong Wang, Li Liu, Hong-Mei Guo, Wei Cong, Wen-Wen Yan, Jun-Ni Huang, Peng Xiao, Chu-Hua Li
Although L-type voltage-dependent calcium channels (VDCCs) have been reported to display different even contrary actions on cognitive functions and long-term potentiation (LTP) formation, there is little information regarding the role of L-type VDCCs in behavioral LTP, a learning-induced LTP model, in the intact brain of freely behaving animals. Here we investigated the effects of verapamil, a non-selective blocker of L-type VDCCs, on behavioral LTP and cognitive functions. Population spikes (PS) were recorded by using electrophysiological methods to examine the role of verapamil in behavioral LTP in the hippocampal dentate gyrus (DG) region...
September 1, 2017: Neurobiology of Learning and Memory
https://www.readbyqxmd.com/read/28836295/microglia-may-compensate-for-dopaminergic-neuron-loss-in-experimental-parkinsonism-through-selective-elimination-of-glutamatergic-synapses-from-the-subthalamic-nucleus
#9
Hitomi Aono, Mohammed Emamussalehin Choudhury, Hiromi Higaki, Kazuya Miyanishi, Yuka Kigami, Kohdai Fujita, Jun-Ichi Akiyama, Hisaaki Takahashi, Hajime Yano, Madoka Kubo, Noriko Nishikawa, Masahiro Nomoto, Junya Tanaka
Parkinson's disease (PD) symptoms do not become apparent until most dopaminergic neurons in the substantia nigra pars compacta (SNc) degenerate, suggesting that compensatory mechanisms play a role. Here, we investigated the compensatory involvement of activated microglia in the SN pars reticulata (SNr) and the globus pallidus (GP) in a 6-hydroxydopamine-induced rat hemiparkinsonism model. Activated microglia accumulated more markedly in the SNr than in the SNc in the model. The cells had enlarged somata and expressed phagocytic markers CD68 and NG2 proteoglycan in a limited region of the SNr, where synapsin I- and postsynaptic density 95-immunoreactivities were reduced...
August 24, 2017: Glia
https://www.readbyqxmd.com/read/28809922/increased-signaling-by-the-autism-related-engrailed-2-protein-enhances-dendritic-branching-and-spine-density-alters-synaptic-structural-matching-and-exaggerates-protein-synthesis
#10
Asma Soltani, Solène Lebrun, Gilles Carpentier, Giulia Zunino, Sandrine Chantepie, Auriane Maïza, Yuri Bozzi, Claire Desnos, François Darchen, Olivier Stettler
Engrailed 1 (En1) and 2 (En2) code for closely related homeoproteins acting as transcription factors and as signaling molecules that contribute to midbrain and hindbrain patterning, to development and maintenance of monoaminergic pathways, and to retinotectal wiring. En2 has been suggested to be an autism susceptibility gene and individuals with autism display an overexpression of this homeogene but the mechanisms remain unclear. We addressed in the present study the effect of exogenously added En2 on the morphology of hippocampal cells that normally express only low levels of Engrailed proteins...
2017: PloS One
https://www.readbyqxmd.com/read/28749340/super-resolution-imaging-of-synaptic-and-extra-synaptic-ampa-receptors-with-different-sized-fluorescent-probes
#11
Sang Hak Lee, Chaoyi Jin, En Cai, Pinghua Ge, Yuji Ishitsuka, Kai Wen Teng, Andre A de Thomaz, Duncan Nall, Murat Baday, Okunola Jeyifous, Daniel Demonte, Christopher M Dundas, Sheldon Park, Jary Y Delgado, William N Green, Paul R Selvin
Previous studies tracking AMPA receptor (AMPAR) diffusion at synapses observed a large mobile extrasynaptic AMPAR pool. Using super-resolution microscopy, we examined how fluorophore size and photostability affected AMPAR trafficking outside of, and within, post-synaptic densities (PSDs) from rats. Organic fluorescent dyes (≈4 nm), quantum dots, either small (≈10 nm diameter; sQDs) or big (>20 nm; bQDs), were coupled to AMPARs via different-sized linkers. We find that >90% of AMPARs labeled with fluorescent dyes or sQDs were diffusing in confined nanodomains in PSDs, which were stable for 15 min or longer...
July 27, 2017: ELife
https://www.readbyqxmd.com/read/28742076/altered-neurite-morphology-and-cholinergic-function-of-induced-pluripotent-stem-cell-derived-neurons-from-a-patient-with-kleefstra-syndrome-and-autism
#12
J Nagy, J Kobolák, S Berzsenyi, Z Ábrahám, H X Avci, I Bock, Z Bekes, B Hodoscsek, A Chandrasekaran, A Téglási, P Dezső, B Koványi, E T Vörös, L Fodor, T Szél, K Németh, A Balázs, A Dinnyés, B Lendvai, G Lévay, V Román
The aim of the present study was to establish an in vitro Kleefstra syndrome (KS) disease model using the human induced pluripotent stem cell (hiPSC) technology. Previously, an autism spectrum disorder (ASD) patient with Kleefstra syndrome (KS-ASD) carrying a deleterious premature termination codon mutation in the EHMT1 gene was identified. Patient specific hiPSCs generated from peripheral blood mononuclear cells of the KS-ASD patient were differentiated into post-mitotic cortical neurons. Lower levels of EHMT1 mRNA as well as protein expression were confirmed in these cells...
July 25, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28741701/dissecting-molecular-architecture-of-post-synaptic-density-at-excitatory-synapses-an-editorial-highlight-for-hierarchical-organization-and-genetically-separable-subfamilies-of-psd95-postsynaptic-supercomplexes-on-page-504
#13
EDITORIAL
Jinjun Chen, Hui-Lin Pan
This Editorial highlights a study by Frank and colleagues (2017) in the current issue of Journal of Neurochemistry. The authors report the genetic composition and stoichiometry of endogenous subfamilies of PSD95-containing supercomplexes in the mouse brain using an innovative strategy of combining gene-tagging knock-in, targeted mutations, and quantitative biochemical assays. Their findings shed new light on our understanding of the genetic hierarchy required for the assembly of distinct supercomplex subfamilies at excitatory synapses in the brain...
August 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28733898/d-cycloserine-ameliorates-autism-like-deficits-by-removing-glua2-containing-ampa-receptors-in-a-valproic-acid-induced-rat-model
#14
Han-Fang Wu, Po See Chen, Ya-Ting Hsu, Chi-Wei Lee, Tzu-Feng Wang, Yi-Ju Chen, Hui-Ching Lin
Valproic acid (VPA)-exposed rat offspring have demonstrated autism spectrum disorder (ASD) phenotypes and impaired N-methyl-D-aspartate receptor (NMDAR)-dependent long-term depression (LTD) in the lateral nucleus of the amygdala. NMDAR partial agonist D-cycloserine (DCS) has been reported to act as a cognitive enhancer by increasing the NMDAR response to improve autistic-like phenotypes in animals. However, the mechanism of DCS in alleviating the ASD is still unknown. Using combined behavioral, electrophysiological, and molecular approaches, we found that DCS administration rescued social interaction deficits and anxiety/repetitive-like behaviors observed in VPA-exposed offspring...
July 21, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28705167/inhibition-of-parkinsonian-tremor-with-cutaneous-afferent-evoked-by-transcutaneous-electrical-nerve-stimulation
#15
Man-Zhao Hao, Shao-Qin Xu, Zi-Xiang Hu, Fu-Liang Xu, Chuan-Xin M Niu, Qin Xiao, Ning Lan
BACKGROUND: Recent study suggests that tremor signals are transmitted by way of multi-synaptic corticospinal pathway. Neurophysiological studies have also demonstrated that cutaneous afferents exert potent inhibition to descending motor commands by way of spinal interneurons. We hypothesize in this study that cutaneous afferents could also affect the transmission of tremor signals, thus, inhibit tremor in patients with PD. METHODS: We tested this hypothesis by activating cutaneous afferents in the dorsal hand skin innervated by superficial radial nerve using transcutaneous electrical nerve stimulation (TENS)...
July 14, 2017: Journal of Neuroengineering and Rehabilitation
https://www.readbyqxmd.com/read/28701928/the-hyperpolarization-activated-current-determines-synaptic-excitability-calcium-activity-and-specific-viability-of-substantia-nigra-dopaminergic-neurons
#16
Carmen Carbone, Alessia Costa, Gustavo Provensi, Guido Mannaioni, Alessio Masi
Differential vulnerability between Substantia Nigra pars compacta (SNpc) and Ventral Tegmental Area (VTA) dopaminergic (DAergic) neurons is a hallmark of Parkinson's disease (PD). Understanding the molecular bases of this key histopathological aspect would foster the development of much-needed disease-modifying therapies. Non-heterogeneous DAergic degeneration is present in both toxin-based and genetic animal models, suggesting that cellular specificity, rather than causing factors, constitutes the background for differential vulnerability...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28697947/synaptic-distribution-and-plasticity-in-primary-auditory-cortex-a1-exhibits-laminar-and-cell-specific-changes-in-the-deaf
#17
H Ruth Clemo, Stephen G Lomber, M Alex Meredith
The processing sequence through primary auditory cortex (A1) is impaired by deafness as evidenced by reduced neuronal activation in A1 of cochlear-implanted deaf cats. Such a loss of neuronal excitation should be manifest as changes in excitatory synaptic number and/or size, for which the post-synaptic correlate is the dendritic spine. Therefore, the present study sought evidence for this functional disruption using Golgi-Cox/light microscopic techniques that examined spine-bearing neurons and their dendritic spine features across all laminae in A1 of early-deaf (ototoxic lesion <1 month; raised into adulthood >16 months) and hearing cats...
July 1, 2017: Hearing Research
https://www.readbyqxmd.com/read/28688852/cdkl5-controls-postsynaptic-localization-of-glun2b-containing-nmda-receptors-in-the-hippocampus-and-regulates-seizure-susceptibility
#18
Kosuke Okuda, Shizuka Kobayashi, Masahiro Fukaya, Aya Watanabe, Takuto Murakami, Mai Hagiwara, Tempei Sato, Hiroe Ueno, Narumi Ogonuki, Sayaka Komano-Inoue, Hiroyuki Manabe, Masahiro Yamaguchi, Atsuo Ogura, Hiroshi Asahara, Hiroyuki Sakagami, Masashi Mizuguchi, Toshiya Manabe, Teruyuki Tanaka
Mutations in the Cyclin-dependent kinase-like 5 (CDKL5) gene cause severe neurodevelopmental disorders accompanied by intractable epilepsies, i.e. West syndrome or atypical Rett syndrome. Here we report generation of the Cdkl5 knockout mouse and show that CDKL5 controls postsynaptic localization of GluN2B-containing N-methyl-d-aspartate (NMDA) receptors in the hippocampus and regulates seizure susceptibility. Cdkl5 -/Y mice showed normal sensitivity to kainic acid; however, they displayed significant hyperexcitability to NMDA...
October 2017: Neurobiology of Disease
https://www.readbyqxmd.com/read/28660571/isolation-of-neuronal-synaptic-membranes-by-sucrose-gradient-centrifugation
#19
Blake R Hopiavuori, Dustin R Masser, Joseph L Wilkerson, Richard S Brush, Nawajes A Mandal, Robert E Anderson, Willard M Freeman
Sucrose gradient centrifugation is a very useful technique for isolating specific membrane types based on their size and density. This is especially useful for detecting fatty acids and lipid molecules that are targeted to specialized membranes. Without fractionation, these types of molecules could be below the levels of detection after being diluted out by the more abundant lipid molecules with a more ubiquitous distribution throughout the various cell membranes. Isolation of specific membrane types where these lipids are concentrated allows for their detection and analysis...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28617434/lispro-mitigates-%C3%AE-amyloid-and-associated-pathologies-in-alzheimer-s-mice
#20
Ahsan Habib, Darrell Sawmiller, Song Li, Yang Xiang, David Rongo, Jun Tian, Huayan Hou, Jin Zeng, Adam Smith, Shengnuo Fan, Brian Giunta, Takashi Mori, Glenn Currier, Douglas Ronald Shytle, Jun Tan
Lithium has been marketed in the United States of America since the 1970s as a treatment for bipolar disorder. More recently, studies have shown that lithium can improve cognitive decline associated with Alzheimer's disease (AD). However, the current United States Food and Drug Administration-approved lithium pharmaceutics (carbonate and citrate chemical forms) have a narrow therapeutic window and unstable pharmacokinetics that, without careful monitoring, can cause serious adverse effects. Here, we investigated the safety profile, pharmacokinetics, and therapeutic efficacy of LISPRO (ionic co-crystal of lithium salicylate and l-proline), lithium salicylate, and lithium carbonate (Li2CO3)...
June 15, 2017: Cell Death & Disease
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