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https://www.readbyqxmd.com/read/29017970/absence-of-microglial-cx3cr1-impairs-the-synaptic-integration-of-adult-born-hippocampal-granule-neurons
#1
M Bolós, J R Perea, J Terreros-Roncal, N Pallas-Bazarra, J Jurado-Arjona, J Ávila, M Llorens-Martín
Microglia are immune cells that play a crucial role in maintaining brain homeostasis. Among the mechanisms of communication between microglia and neurons, the CX3CL1/CX3CR1 axis exerts a central modulatory role. Animals lacking CX3CR1 microglial receptor (CX3CR1-/- mice) exhibit marked alterations not only in microglia but also in neurons located in various regions of the brain. Here we show that microglial depletion of CX3CR1 leads to the deficient synaptic integration of adult-born granule neurons in the dentate gyrus (DG), both at the afferent and efferent level...
October 7, 2017: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/28948967/corticostriatal-circuit-defects-in-hoxb8-mutant-mice
#2
N Nagarajan, B W Jones, P J West, R E Marc, M R Capecchi
Hoxb8 mutant mice exhibit compulsive grooming and hair removal dysfunction similar to humans with the obsessive-compulsive disorder (OCD)-spectrum disorder, trichotillomania. As, in the mouse brain, the only detectable cells that label with Hoxb8 cell lineage appear to be microglia, we suggested that defective microglia cause the neuropsychiatric disorder. Does the Hoxb8 mutation in microglia lead to neural circuit dysfunctions? We demonstrate that Hoxb8 mutants contain corticostriatal circuit defects. Golgi staining, ultra-structural and electrophysiological studies of mutants reveal excess dendritic spines, pre- and postsynaptic structural defects, long-term potentiation and miniature postsynaptic current defects...
September 26, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28771976/hdac3-negatively-regulates-spatial-memory-in-a-mouse-model-of-alzheimer-s-disease
#3
Xiaolei Zhu, Sulei Wang, Linjie Yu, Jiali Jin, Xing Ye, Yi Liu, Yun Xu
The accumulation and deposition of beta-amyloid (Aβ) is a key neuropathological hallmark of Alzheimer's disease (AD). Histone deacetylases (HDACs) are promising therapeutic targets for the treatment of AD, while the specific HDAC isoforms associated with cognitive improvement are poorly understood. In this study, we investigate the role of HDAC3 in the pathogenesis of AD. Nuclear HDAC3 is significantly increased in the hippocampus of 6- and 9-month-old APPswe/PS1dE9 (APP/PS1) mice compared with that in age-matched wild-type C57BL/6 (B6) mice...
October 2017: Aging Cell
https://www.readbyqxmd.com/read/28729191/hypothermia-pretreatment-improves-cognitive-impairment-via-enhancing-synaptic-plasticity-in-a-traumatic-brain-injury-model
#4
Bingjin Liu, Lin Wang, Yun Cao, Weiqi Xu, Fangxiao Shi, Qing Tian, Xinwen Zhou
PosttraumatichypothermiaattenuatescognitivedeficitscausedbyTBIwhen it is administered at an early stage. However, little is known regarding the effect of hypothermia pretreatment on cognitive deficits one month after TBI. In the current study, the behavior test revealed that hypothermia pretreatment mitigates the learning and memory impairment induced by TBI in mice. Hypothermia treatment significantly increased the expression of PSD93, PSD95 and NR2B one month after TBI in the cortex and hippocampus compared with the normothermia group...
July 17, 2017: Brain Research
https://www.readbyqxmd.com/read/28697890/stress-induced-neuronal-colony-stimulating-factor-1-provokes-microglia-mediated-neuronal-remodeling-and-depressive-like-behavior
#5
Eric S Wohleb, Rosemarie Terwilliger, Catharine H Duman, Ronald S Duman
BACKGROUND: Chronic stress exposure causes neuronal atrophy and synaptic deficits in the medial prefrontal cortex (PFC), contributing to development of anxiety- and depressive-like behaviors. Concomitantly, microglia in the PFC undergo morphological and functional changes following stress exposure, suggesting that microglia contribute to synaptic deficits underlying behavioral consequences. METHODS: Male and female mice were exposed to chronic unpredictable stress (CUS) to examine the role of neuron-microglia interactions in the medial PFC during development of anxiety- and depressive-like behaviors...
June 12, 2017: Biological Psychiatry
https://www.readbyqxmd.com/read/28623134/dysfunction-in-diurnal-synaptic-responses-and-social-behavior-abnormalities-in-cathepsin-s-deficient-mice
#6
Fumiko Takayama, Xinwen Zhang, Yoshinori Hayashi, Zhou Wu, Hiroshi Nakanishi
The expression of cathepsin S (CatS), a microglia-specific lysosomal cysteine protease in the brain, is regulated by the intrinsic microglial circadian clock. We herein report that the diurnal variation of evoked synaptic responses of cortical neurons disappeared in cathepsin S-deficient (CatS(-/-)) mice. The dendritic spine density of the cortical neurons was significantly reduced by incubation with a recombinant CatS. Furthermore, CatS(-/-) mice exhibited impaired social interaction and social novelty recognition in the three-chamber test...
August 19, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28606182/microglia-limit-the-expansion-of-%C3%AE-amyloid-plaques-in-a-mouse-model-of-alzheimer-s-disease
#7
Ruohe Zhao, Wanling Hu, Julia Tsai, Wei Li, Wen-Biao Gan
BACKGROUND: Microglia are known as resident immune cells in the brain. β-amyloid (Aβ) plaques in the brain of Alzheimer's disease (AD) are surrounded by microglia, but whether and how microglia affect the formation and maintenance of plaques remains controversial. METHODS: We depleted microglia by injecting diphtheria toxin (DT) in CX 3 CR1 (CreER/+) :R26 (DTR/+) (CX 3 CR1-iDTR) mice crossed with APPswe/PSEN1dE9 (APP/PS1) mice. Intravital time-lapse imaging was performed to examine changes in the number and size of Congo Red-labeled amyloid plaques over 1-2 weeks...
June 12, 2017: Molecular Neurodegeneration
https://www.readbyqxmd.com/read/28588483/plastic-and-neuroprotective-mechanisms-involved-in-the-therapeutic-effects-of-cannabidiol-in-psychiatric-disorders
#8
REVIEW
Alline C Campos, Manoela V Fogaça, Franciele F Scarante, Sâmia R L Joca, Amanda J Sales, Felipe V Gomes, Andreza B Sonego, Naielly S Rodrigues, Ismael Galve-Roperh, Francisco S Guimarães
Beneficial effects of cannabidiol (CBD) have been described for a wide range of psychiatric disorders, including anxiety, psychosis, and depression. The mechanisms responsible for these effects, however, are still poorly understood. Similar to clinical antidepressant or atypical antipsychotic drugs, recent findings clearly indicate that CBD, either acutely or repeatedly administered, induces plastic changes. For example, CBD attenuates the decrease in hippocampal neurogenesis and dendrite spines density induced by chronic stress and prevents microglia activation and the decrease in the number of parvalbumin-positive GABA neurons in a pharmacological model of schizophrenia...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28579942/voluntary-exercise-promotes-glymphatic-clearance-of-amyloid-beta-and-reduces-the-activation-of-astrocytes-and-microglia-in-aged-mice
#9
Xiao-Fei He, Dong-Xu Liu, Qun Zhang, Feng-Ying Liang, Guang-Yan Dai, Jin-Sheng Zeng, Zhong Pei, Guang-Qing Xu, Yue Lan
Age is characterized by chronic inflammation, leading to synaptic dysfunction and dementia because the clearance of protein waste is reduced. The clearance of proteins depends partly on the permeation of the blood-brain barrier (BBB) or on the exchange of water and soluble contents between the cerebrospinal fluid (CSF) and the interstitial fluid (ISF). A wealth of evidence indicates that physical exercise improves memory and cognition in neurodegenerative diseases during aging, such as Alzheimer's disease (AD), but the influence of physical training on glymphatic clearance, BBB permeability and neuroinflammation remains unclear...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28487495/naoling-decoction-restores-cognitive-function-by-inhibiting-the-neuroinflammatory-network-in-a-rat-model-of-alzheimer-s-disease
#10
Zian Xia, Weijun Peng, Shunhua Cheng, Bingwu Zhong, Chenxia Sheng, Chunhu Zhang, Wei Gong, Shuai Cheng, Jun Li, Zhe Wang
Neuroinflammation is central to the pathogenesis of Alzheimer's disease (AD). We previously showed that Naoling decoction (NLD), a traditional Chinese medicine, was effective against AD, acting by inhibiting expression of IL-1β and IL-6. In the present study, we generated the rat model of AD by injecting Aβ1-42 peptide intracerebroventricularly and evaluated the dose-dependent effects of NLD treatment. The NLD-treated rats exhibited significant improvements in cognitive function as evaluated by the Morris water maze test...
June 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28386309/kiwifruit-alleviates-learning-and-memory-deficits-induced-by-pb-through-antioxidation-and-inhibition-of-microglia-activation-in-vitro-and-in-vivo
#11
Wei-Zhen Xue, Qian-Qian Yang, Yiwen Chen, Rong-Xin Zou, Dong Xing, Yi Xu, Yong-Sheng Liu, Hui-Li Wang
Lead (Pb) exposure, in particular during early postnatal life, increases susceptibility to cognitive dysfunction and neurodegenerative outcomes. The detrimental effect of Pb exposure is basically due to an increasing ROS production which overcomes the antioxidant systems and finally leads to cognitive dysfunction. Kiwifruit is rich in the antioxidants like vitamin C and polyphenols. This study aims to investigate the effects and mechanism of kiwifruit to alleviate learning and memory deficits induced by Pb exposure...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/28248542/two-photon-laser-scanning-microscopy-for-single-and-repetitive-imaging-of-dorsal-and-lateral-spinal-white-matter-in-vivo
#12
F Nadrigny, K Le Meur, H Steffens, E D Schomburg, S Safavi-Abbasi, P Dibaj
We developed appropriate surgical procedures for single and repetitive multi-photon imaging of spinal cord in vivo. By intravenous anesthesia, artificial ventilation and laminectomy, acute experiments were performed in the dorsal and lateral white matter. By volatile anesthesia and minimal-invasive surgery, chronic repetitive imaging up to 8 months were performed in the dorsal column through the window between two adjacent spines. Transgenic mouse technology enabled simultaneous imaging of labeled axons, astrocytes and microglia...
February 28, 2017: Physiological Research
https://www.readbyqxmd.com/read/28245754/treatment-of-traumatic-brain-injury-in-rats-with-n-acetyl-seryl-aspartyl-lysyl-proline
#13
Yanlu Zhang, Zheng Gang Zhang, Michael Chopp, Yuling Meng, Li Zhang, Asim Mahmood, Ye Xiong
OBJECTIVE The authors' previous studies have suggested that thymosin beta 4 (Tβ4), a major actin-sequestering protein, improves functional recovery after neural injury. N-acetyl-seryl-aspartyl-lysyl-proline (AcSDKP) is an active peptide fragment of Tβ4. Its effect as a treatment of traumatic brain injury (TBI) has not been investigated. Thus, this study was designed to determine whether AcSDKP treatment improves functional recovery in rats after TBI. METHODS Young adult male Wistar rats were randomly divided into the following groups: 1) sham group (no injury); 2) TBI + vehicle group (0...
March 2017: Journal of Neurosurgery
https://www.readbyqxmd.com/read/28123022/tnf-%C3%AE-differentially-regulates-synaptic-plasticity-in-the-hippocampus-and-spinal-cord-by-microglia-dependent-mechanisms-after-peripheral-nerve-injury
#14
Yong Liu, Li-Jun Zhou, Jun Wang, Dai Li, Wen-Jie Ren, Jiyun Peng, Xiao Wei, Ting Xu, Wen-Jun Xin, Rui-Ping Pang, Yong-Yong Li, Zhi-Hai Qin, Madhuvika Murugan, Mark P Mattson, Long-Jun Wu, Xian-Guo Liu
Clinical studies show that chronic pain is accompanied by memory deficits and reduction in hippocampal volume. Experimental studies show that spared nerve injury (SNI) of the sciatic nerve induces long-term potentiation (LTP) at C-fiber synapses in spinal dorsal horn, but impairs LTP in the hippocampus. The opposite changes may contribute to neuropathic pain and memory deficits, respectively. However, the cellular and molecular mechanisms underlying the functional synaptic changes are unclear. Here, we show that the dendrite lengths and spine densities are reduced significantly in hippocampal CA1 pyramidal neurons, but increased in spinal neurokinin-1-positive neurons in mice after SNI, indicating that the excitatory synaptic connectivity is reduced in hippocampus but enhanced in spinal dorsal horn in this neuropathic pain model...
January 25, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28120640/blockade-of-nmda-receptors-decreased-spinal-microglia-activation-in-bee-venom-induced-acute-inflammatory-pain-in-rats
#15
Li Li, Yongfang Wu, Zhifeng Bai, Yuyan Hu, Wenbin Li
OBJECTIVES: Microglial cells in spinal dorsal horn can be activated by nociceptive stimuli and the activated microglial cells release various cytokines enhancing the nociceptive transmission. However, the mechanisms underlying the activation of spinal microglia during nociceptive stimuli have not been well understood. In order to define the role of NMDA receptors in the activation of spinal microglia during nociceptive stimuli, the present study was undertaken to investigate the effect of blockade of NMDA receptors on the spinal microglial activation induced by acute peripheral inflammatory pain in rats...
March 2017: Neurological Research
https://www.readbyqxmd.com/read/28007586/role-of-microglia-disturbances-and-immune-related-marker-abnormalities-in-cortical-circuitry-dysfunction-in-schizophrenia
#16
REVIEW
David W Volk
Studies of genetics, serum cytokines, and autoimmune illnesses suggest that immune-related abnormalities are involved in the disease process of schizophrenia. Furthermore, direct evidence of cortical immune activation, including markedly elevated levels of many immune-related markers, have been reported in the prefrontal cortex in multiple cohorts of schizophrenia subjects. Within the prefrontal cortex in schizophrenia, deficits in the basilar dendritic spines of layer 3 pyramidal neurons and disturbances in inhibitory inputs to pyramidal neurons have also been commonly reported...
March 2017: Neurobiology of Disease
https://www.readbyqxmd.com/read/27998892/tnf-%C3%AE-differentially-regulates-synaptic-plasticity-in-the-hippocampus-and-spinal-cord-by-microglia-dependent-mechanisms-after-peripheral-nerve-injury
#17
Yong Liu, Li-Jun Zhou, Jun Wang, Dai Li, Wen-Jie Ren, Jiyun Peng, Xiao Wei, Ting Xu, Wen-Jun Xin, Rui-Ping Pang, Yong-Yong Li, Zhi-Hai Qin, Madhuvika Murugan, Mark P Mattson, Long-Jun Wu, Xian-Guo Liu
Clinical studies show that chronic pain is accompanied by memory deficits and reduction in hippocampal volume. Experimental studies show that spared nerve injury (SNI) of sciatic nerve induces long-term potentiation (LTP) at C-fiber synapses in spinal dorsal horn but impairs LTP in hippocampus. The opposite changes may contribute to neuropathic pain and memory deficits, respectively. However, the cellular and molecular mechanisms underlying the functional synaptic changes are unclear. Here we show that the dendrite lengths and spine densities are significantly reduced in hippocampal CA1 pyramidal neurons but increased in spinal neurokinin-1-positive neurons in mice after SNI, indicating that the excitatory synaptic connectivity is reduced in hippocampus but enhanced in spinal dorsal horn in this neuropathic pain model...
December 20, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27878757/targeting-ccr3-to-reduce-amyloid-%C3%AE-production-tau-hyperphosphorylation-and-synaptic-loss-in-a-mouse-model-of-alzheimer-s-disease
#18
Chunyan Zhu, Bing Xu, Xiaohong Sun, Qiwen Zhu, Yi Sui
The majority of Alzheimer's disease (AD) patients have a late onset, and chronic neuroinflammation, characterized by glial activation and secretion of pro-inflammatory cytokines and chemokines, plays a role in the pathogenesis of AD. The chemokine CCL11 has been shown to be a causative factor of cognitive decline in the process of aging, but little is known whether it is involved in the pathogenesis of AD. In the present study, we showed that CCR3, the receptor for CCL11, was expressed by hippocampal neurons and treatment of primary hippocampal neuronal cultures (14 days in vitro) with CCL11 resulted in activation of cyclin-dependent kinase 5 and glycogen synthase kinase-3β, associated with elevated tau phosphorylation at multiple sites...
November 23, 2016: Molecular Neurobiology
https://www.readbyqxmd.com/read/27794462/long-term-depression-associated-signaling-is-required-for-an-in-vitro-model-of-nmda-receptor-dependent-synapse-pruning
#19
Maile A Henson, Charles J Tucker, Meilan Zhao, Serena M Dudek
Activity-dependent pruning of synaptic contacts plays a critical role in shaping neuronal circuitry in response to the environment during postnatal brain development. Although there is compelling evidence that shrinkage of dendritic spines coincides with synaptic long-term depression (LTD), and that LTD is accompanied by synapse loss, whether NMDA receptor (NMDAR)-dependent LTD is a required step in the progression toward synapse pruning is still unknown. Using repeated applications of NMDA to induce LTD in dissociated rat neuronal cultures, we found that synapse density, as measured by colocalization of fluorescent markers for pre- and postsynaptic structures, was decreased irrespective of the presynaptic marker used, post-treatment recovery time, and the dendritic location of synapses...
February 2017: Neurobiology of Learning and Memory
https://www.readbyqxmd.com/read/27697456/prenatal-infection-leads-to-asd-like-behavior-and-altered-synaptic-pruning-in-the-mouse-offspring
#20
Lourdes Fernández de Cossío, Andrea Guzmán, Suzanne van der Veldt, Giamal N Luheshi
Environmental challenges to the maternal immune system during pregnancy have been associated with an increase in the frequency of neurodevelopmental disorders such as Autism Spectrum Disorders (ASD) appearing in the offspring. Microglia, the brain's resident immune-cells, are now known to be critically involved in normal brain development, shaping connections between neurons by pruning superfluous synaptic spines. Our aim was to investigate whether maternal infection during critical stages of gestation compromises the role of microglia in sculpting neuronal circuits...
September 30, 2016: Brain, Behavior, and Immunity
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