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https://www.readbyqxmd.com/read/28723268/assay-of-calcium-transients-and-synapses-in-rat-hippocampal-neurons-by-kinetic-image-cytometry-and-high-content-analysis-an-in-vitro-model-system-for-postchemotherapy-cognitive-impairment
#1
Patrick M McDonough, Natalie L Prigozhina, Ranor C B Basa, Jeffrey H Price
Postchemotherapy cognitive impairment (PCCI) is commonly exhibited by cancer patients treated with a variety of chemotherapeutic agents, including the endocrine disruptor tamoxifen (TAM). The etiology of PCCI is poorly understood. Our goal was to develop high-throughput assay methods to test the effects of chemicals on neuronal function applicable to PCCI. Rat hippocampal neurons (RHNs) were plated in 96- or 384-well dishes and exposed to test compounds (forskolin [FSK], 17β-estradiol [ES]), TAM or fulvestrant [FUL], aka ICI 182,780) for 6-14 days...
July 2017: Assay and Drug Development Technologies
https://www.readbyqxmd.com/read/28720484/long-term-enzyme-replacement-therapy-improves-neurocognitive-functioning-and-hippocampal-synaptic-plasticity-in-immune-tolerant-alpha-mannosidosis-mice
#2
Stijn Stroobants, Markus Damme, Ann Van der Jeugd, Ben Vermaercke, Claes Andersson, Jens Fogh, Paul Saftig, Judith Blanz, Rudi D'Hooge
Alpha-mannosidosis is a glycoproteinosis caused by deficiency of lysosomal acid alpha-mannosidase (LAMAN), which markedly affects neurons of the central nervous system (CNS), and causes pathognomonic intellectual dysfunction in the clinical condition. Cognitive improvement consequently remains a major therapeutic objective in research on this devastating genetic error. Immune-tolerant LAMAN knockout mice were developed to evaluate the effects of enzyme replacement therapy (ERT) by prolonged administration of recombinant human enzyme...
July 15, 2017: Neurobiology of Disease
https://www.readbyqxmd.com/read/28701415/structure-of-psd-95-map1a-complex-reveals-unique-target-recognition-mode-of-maguk-gk-domain
#3
Yitan Xia, Yuan Shang, Rongguang Zhang, Jinwei Zhu
The PSD-95 family of membrane-associated guanylate kinases (MAGUKs) are major synaptic scaffold proteins and play crucial roles in the dynamic regulation of dendritic remodeling which is understood to be the foundation of synaptogenesis and synaptic plasticity. The guanylate kinase (GK) domain of MAGUK family proteins functions as a phosphor-peptide binding module. However, the GK domain of PSD-95 has been found to directly bind to a peptide sequence within the C-terminal region of neuronal-specific microtubule-associated protein 1A (MAP1A), though the detailed molecular mechanism governing this phosphorylation-independent interaction at the atomic level is missing...
July 12, 2017: Biochemical Journal
https://www.readbyqxmd.com/read/28698933/distinct-effects-on-the-dendritic-arbor-occur-by-microbead-versus-bath-administration-of-brain-derived-neurotrophic-factor
#4
Kate M O'Neill, Munjin Kwon, Katherine E Donohue, Bonnie L Firestein
Proper communication among neurons depends on an appropriately formed dendritic arbor, and thus, aberrant changes to the arbor are implicated in many pathologies, ranging from cognitive disorders to neurodegenerative diseases. Due to the importance of dendritic shape to neuronal network function, the morphology of dendrites is tightly controlled and is influenced by both intrinsic and extrinsic factors. In this work, we examine how brain-derived neurotrophic factor (BDNF), one of the most well-studied extrinsic regulators of dendritic branching, affects the arbor when it is applied locally via microbeads to cultures of hippocampal neurons...
July 11, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/28692247/site-specific-phosphorylation-of-psd-95-pdz-domains-reveals-fine-tuned-regulation-of-protein-protein-interactions
#5
Søren W Pedersen, Louise Albertsen, Griffin E Moran, Brie Levesque, Stine B Pedersen, Lina Bartels, Hannah Wapenaar, Fe Yei, Mingjie Zhang, Mark E Bowen, Kristian Strømgaard
The postsynaptic density protein of 95 kDa (PSD-95) is a key scaffolding protein that controls signaling at synapses in the brain through interactions of its PDZ domains with the C-termini of receptors, ion channels and enzymes. PSD-95 is highly regulated by phosphorylation. To explore the effect of phosphorylation on PSD-95, we used semisynthetic strategies to introduce phosphorylated amino acids at four positions within the PDZ domains and examined the effects on interactions with a large set of binding partners...
July 10, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/28645745/dna-methylation-of-dlg4-and-gja-1-of-human-hippocampus-and-prefrontal-cortex-in-major-depression-is-unchanged-in-comparison-to-healthy-individuals
#6
Oliver Kaut, Amit Sharma, Ina Schmitt, René Hurlemann, Ullrich Wüllner
Epigenetic alterations provide a potential mechanism to account for the numerous gene-environment interactions that have been reported in association with neuropsychiatric phenotypes. In context to major depression disorder (MDD), where postmortem and neuroimaging studies provide insights into dysfunctional brain regions, involvement of genetic heterogeneity also revealed the complexity of this disorder. Despite intensive research during the past several decades and information from genome wide studies, pathophysiology of depressive disorders remained elusive...
June 20, 2017: Journal of Clinical Neuroscience: Official Journal of the Neurosurgical Society of Australasia
https://www.readbyqxmd.com/read/28630404/activation-of-d1r-pka-mtor-signaling-cascade-in-medial-prefrontal-cortex-underlying-the-antidepressant-effects-of-l-spd
#7
Bing Zhang, Fei Guo, Yuqin Ma, Yingcai Song, Rong Lin, Fu-Yi Shen, Guo-Zhang Jin, Yang Li, Zhi-Qiang Liu
Major depressive disorder (MDD) is a common neuropsychiatric disorder characterized by diverse symptoms. Although several antidepressants can influence dopamine system in the medial prefrontal cortex (mPFC), but the role of D1R or D2R subtypes of dopamine receptor during anti-depression process is still vague in PFC region. To address this question, we investigate the antidepressant effect of levo-stepholidine (l-SPD), an antipsychotic medication with unique pharmacological profile of D1R agonism and D2R antagonism, and clarified its molecular mechanisms in the mPFC...
June 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28623607/presenilin-1-targeted-morpholino-induces-cognitive-deficits-increased-brain-a%C3%AE-1-42-and-decreased-synaptic-marker-psd-95-in-zebrafish-larvae
#8
Laura Roesler Nery, Natalia Eltz Silva, Raphaela Fonseca, Monica Ryff Moreira Vianna
Presenilins are transmembrane proteases required for the proteolytic cleavage of Notch and also act as the catalytic core of the γ-secretase complex, which is responsible for the final cleavage of the amyloid precursor protein into Amyloid-β (Aβ) peptides of varying lengths. Presenilin-1 gene (psen1) mutations are the main cause of early-onset autosomal-dominant Familial Alzheimer Disease. Elucidating the roles of Presenilin-1 and other hallmark proteins involved in Alzheimer's disease is crucial for understanding the disease etiology and underlying molecular mechanisms...
June 16, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/28604739/autism-like-behaviours-and-enhanced-memory-formation-and-synaptic-plasticity-in-lrfn2-salm1-deficient-mice
#9
Naoko Morimura, Hiroki Yasuda, Kazuhiko Yamaguchi, Kei-Ichi Katayama, Minoru Hatayama, Naoko H Tomioka, Maya Odagawa, Akiko Kamiya, Yoshimi Iwayama, Motoko Maekawa, Kazuhiko Nakamura, Hideo Matsuzaki, Masatsugu Tsujii, Kazuyuki Yamada, Takeo Yoshikawa, Jun Aruga
Lrfn2/SALM1 is a PSD-95-interacting synapse adhesion molecule, and human LRFN2 is associated with learning disabilities. However its role in higher brain function and underlying mechanisms remain unknown. Here, we show that Lrfn2 knockout mice exhibit autism-like behavioural abnormalities, including social withdrawal, decreased vocal communications, increased stereotyped activities and prepulse inhibition deficits, together with enhanced learning and memory. In the hippocampus, the levels of synaptic PSD-95 and GluA1 are decreased...
June 12, 2017: Nature Communications
https://www.readbyqxmd.com/read/28602762/different-patterns-of-changes-between-actin-dynamics-and-synaptic-density-in-the-rat-s-primary-visual-cortex-during-a-special-period-of-visual-development
#10
Mei-Qing Chen, Ai-Ling Bi, Yue-Ying Zhang, Qin Yan, Yuan-Yuan Sun, Xiu-Yan Zhang, Xian-Zhen Ma, Hong-Sheng Bi
In our previous study, we found that the normalized levels of the synaptosomal filament actin (F-actin) to monomeric global actin (G-actin) ratio in the primary visual cortex (V1) of rats was significantly lower on postnatal day (P) 45 compared with P30, however, the synaptic density in the monocular area of primary visual cortex (V1M) maintained a stable high level from P30 to P45. The mechanisms underlying the different patterned of change in synaptic density and actin rearrangements from P30 to P45 are unclear...
June 2017: Brain Research Bulletin
https://www.readbyqxmd.com/read/28593193/differential-expression-and-cell-type-specificity-of-perineuronal-nets-in-hippocampus-medial-entorhinal-cortex-and-visual-cortex-examined-in-the-rat-and-mouse
#11
Kristian Kinden Lensjø, Ane Charlotte Christensen, Simen Tennøe, Marianne Fyhn, Torkel Hafting
Perineuronal nets (PNNs) are specialized extracellular matrix (ECM) structures that condense around the soma and proximal dendrites of subpopulations of neurons. Emerging evidence suggests that they are involved in regulating brain plasticity. However, the expression of PNNs varies between and within brain areas. A lack of quantitative studies describing the distribution and cell-specificity of PNNs makes it difficult to reveal the functional roles of PNNs. In the current study, we examine the distribution of PNNs and the identity of PNN-enwrapped neurons in three brain areas with different cognitive functions: the dorsal hippocampus, medial entorhinal cortex (mEC) and primary visual cortex (V1)...
May 2017: ENeuro
https://www.readbyqxmd.com/read/28576729/afferent-synaptogenesis-between-ectopic-hair-cell-like-cells-and-neurites-of-spiral-ganglion-induced-by-atoh1-in-mammals-in-vitro
#12
Wen-Wei Luo, Rui Ma, Xiang Cheng, Xiao-Yu Yang, Zhao Han, Dong-Dong Ren, Ping Chen, Fang-Lu Chi, Juan-Mei Yang
Newly formed ectopic hair-cell-like cells (EHCLCs) induced by overexpression of atonal homolog 1 (Atoh1) in vitro were found to possess features of endogenous hair cells (HCs) in previous reports and in the present study. However, limited information is available regarding whether EHCLCs and native spiral ganglion neurons (SGNs) form afferent synapses, which are important for the restoration of hearing. In the current study, we focused on the afferent synaptogenesis between EHCLCs and SGN-derived dendrites...
May 31, 2017: Neuroscience
https://www.readbyqxmd.com/read/28576649/anti-androgenic-effects-of-bisphenol-a-on-spatial-memory-and-synaptic-plasticity-of-the-hippocampus-in-mice
#13
Zhaoqing Fang, Qingjie Zhu, Ting Gu, Xiuying Shen, Yang Yang, Yufeng Liang, Zigui Zhang, Xiaohong Xu
Bisphenol-A (BPA) is a common environmental endocrine disruptor. Our recent studies found that exposure to BPA in both adolescent and adulthood sex-specifically impaired spatial memory in male mice. In this study, 11-week-old gonadectomied (GDX) male mice daily received subcutaneous injections of testosterone propionate (TP, 0.5mg/kg), TP and BPA (0.4 and 4mg/kg), or vehicle for 45days. The results of Morris water maze task showed that exposure to BPA did not affect the spatial memory of GDX mice but impaired that of sham (4mg/kg/day) and TP-treated GDX mice (0...
June 8, 2017: Hormones and Behavior
https://www.readbyqxmd.com/read/28575866/catalpol-protects-synaptic-proteins-from-beta-amyloid-induced-neuron-injury-and-improves-cognitive-functions-in-aged-rats
#14
Zhiming Xia, Fengfei Wang, Shuang Zhou, Rui Zhang, Fushun Wang, Jason H Huang, Erxi Wu, Yongfang Zhang, Yaer Hu
Synapse loss is one of the common factors contributing to cognitive disorders, such as Alzheimer's disease (AD), which is manifested by the impairment of basic cognitive functions including memory processing, perception, problem solving, and language. The current therapies for patients with cognitive disorders are mainly palliative; thus, regimens preventing and/or delaying dementia progression are urgently needed. In this study, we evaluated the effects of catalpol, isolated from traditional Chinese medicine Rehmannia glutinosa, on synaptic plasticity in aged rat models...
May 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/28575743/igf-ii-promotes-neuroprotection-and-neuroplasticity-recovery-in-a-long-lasting-model-of-oxidative-damage-induced-by-glucocorticoids
#15
E Martín-Montañez, C Millon, F Boraldi, F Garcia-Guirado, C Pedraza, E Lara, L J Santin, J Pavia, M Garcia-Fernandez
Insulin-like growth factor-II (IGF-II) is a naturally occurring hormone that exerts neurotrophic and neuroprotective properties in a wide range of neurodegenerative diseases and ageing. Accumulating evidence suggests that the effects of IGF-II in the brain may be explained by its binding to the specific transmembrane receptor, IGFII/M6P receptor (IGF-IIR). However, relatively little is known regarding the role of IGF-II through IGF-IIR in neuroprotection. Here, using adult cortical neuronal cultures, we investigated whether IGF-II exhibits long-term antioxidant effects and neuroprotection at the synaptic level after oxidative damage induced by high and transient levels of corticosterone (CORT)...
May 26, 2017: Redox Biology
https://www.readbyqxmd.com/read/28570537/brain-membrane-fractionation-an-ex-vivo-approach-to-assess-subsynaptic-protein-localization
#16
Xavier Morató, Marc López-Cano, Paula M Canas, Rodrigo A Cunha, Francisco Ciruela
Assessing the synaptic protein composition and function constitutes an important challenge in neuroscience. However, it is not easy to evaluate neurotransmission that occurs within synapses because it is highly regulated by dynamic protein-protein interactions and phosphorylation events. Accordingly, when any method is used to study synaptic transmission, a major goal is to preserve these transient physiological modifications. Here, we present a brain membrane fractionation protocol that represents a robust procedure to isolate proteins belonging to different synaptic compartments...
May 12, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28555636/pyk2-modulates-hippocampal-excitatory-synapses-and-contributes-to-cognitive-deficits-in-a-huntington-s-disease-model
#17
Albert Giralt, Veronica Brito, Quentin Chevy, Clémence Simonnet, Yo Otsu, Carmen Cifuentes-Díaz, Benoit de Pins, Renata Coura, Jordi Alberch, Sílvia Ginés, Jean-Christophe Poncer, Jean-Antoine Girault
The structure and function of spines and excitatory synapses are under the dynamic control of multiple signalling networks. Although tyrosine phosphorylation is involved, its regulation and importance are not well understood. Here we study the role of Pyk2, a non-receptor calcium-dependent protein-tyrosine kinase highly expressed in the hippocampus. Hippocampal-related learning and CA1 long-term potentiation are severely impaired in Pyk2-deficient mice and are associated with alterations in NMDA receptors, PSD-95 and dendritic spines...
May 30, 2017: Nature Communications
https://www.readbyqxmd.com/read/28555345/new-insights-on-temporal-lobe-epilepsy-based-on-plasticity-related-network-changes-and-high-order-statistics
#18
REVIEW
Erika Reime Kinjo, Pedro Xavier Royero Rodríguez, Bianca Araújo Dos Santos, Guilherme Shigueto Vilar Higa, Mariana Sacrini Ayres Ferraz, Christian Schmeltzer, Sten Rüdiger, Alexandre Hiroaki Kihara
Epilepsy is a disorder of the brain characterized by the predisposition to generate recurrent unprovoked seizures, which involves reshaping of neuronal circuitries based on intense neuronal activity. In this review, we first detailed the regulation of plasticity-associated genes, such as ARC, GAP-43, PSD-95, synapsin, and synaptophysin. Indeed, reshaping of neuronal connectivity after the primary, acute epileptogenesis event increases the excitability of the temporal lobe. Herein, we also discussed the heterogeneity of neuronal populations regarding the number of synaptic connections, which in the theoretical field is commonly referred as degree...
May 29, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28554889/development-of-glutamatergic-proteins-in-human-visual-cortex-across-the-lifespan
#19
Caitlin R Siu, Simon P Beshara, David G Jones, Kathryn M Murphy
Traditionally, human primary visual cortex (V1) has been thought to mature within the first few years of life, based on anatomical studies of synapse formation, and establishment of intra- and inter-cortical connections. Human vision, however, develops well beyond the first few years. Previously, we found prolonged development of some GABAergic proteins in human V1 (Pinto et al., 2010). Yet as over 80% of synapses in V1 are excitatory, it remains unanswered if the majority of synapses regulating experience-dependent plasticity and receptive field properties develop late like their inhibitory counterparts...
May 29, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28554200/the-memory-enhancing-effects-of-liquiritigenin-by-activation-of-nmda-receptors-and-the-creb-signaling-pathway-in-mice
#20
Yong-Hyun Ko, Seung-Hwan Kwon, Ji-Young Hwang, Kyung-In Kim, Jee-Yeon Seo, Thi-Lien Nguyen, Seok-Yong Lee, Hyoung-Chun Kim, Choon-Gon Jang
Liquiritigenin (LQ) is a flavonoid that can be isolated from Glycyrrhiza radix. It is frequently used as a tranditional oriental medicine herbal treatment for swelling and injury and for detoxification. However, the effects of LQ on cognitive function have not been fully explored. In this study, we evaluated the memory-enhancing effects of LQ and the underlying mechanisms with a focus on the N-methyl-D-aspartic acid receptor (NMDAR) in mice. Learning and memory ability were evaluated with the Y-maze and passive avoidance tests following administration of LQ...
May 30, 2017: Biomolecules & Therapeutics
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