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Effects of CXCR7-neutralizing antibody on neurogenesis in the hippocampal dentate gyrus and cognitive function in the chronic phase of cerebral ischemia

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Neural Regeneration Research 2020年第6期15卷 1079-1085页

作者： Bing-Chao Dong Mei-Xuan Li Xiao-Yin Wang Xi Cheng Yu Wang Ting Xiao Jukka Jolkkonen Chuan-Sheng Zhao Shan-Shan Zhao Department of Neurology The First Hospital of China Medical UniversityShenyangLiaoning ProvinceChina Key Laboratory of Immunodermatology Ministry of HealthMinistry of EducationShenyangLiaoning ProvinceChina Department of Neurology Institute of Clinical MedicineUniversity of Eastern FinlandKuopioFinland

Stromal cell-derived factor-1 and its receptor CXCR4 are essential regulators of the neurogenesis that occurs in the adult hippocampal dentate gyrus.However,the effects of CXCR7,a new atypical receptor of stromal cell-derived factor-1,on hippocampal neurogenesis after a stroke remain largely unknown.Our study is the first to investigate the effect of a CXCR7-neutralizing antibody on neurogenesis in the dentate gyrus and the associated recovery of cognitive function of rats in the chronic stage of cerebral ischemia.The rats were randomly divided into sham,sham+anti-CXCR7,ischemia and ischemia+anti-CXCR7 groups.Endothelin-1 was injected in the ipsilateral motor cortex and striatum to induce focal cerebral ischemia.Sham group rats were injected with saline instead of endothelin-1 via intracranial injection.Both sham and ischemic rats were treated with intraventricular infusions of CXCR7-neutralizing antibodies for 6 days 1 week after surgery.Immunofluorescence staining with doublecortin,a marker for neuronal precursors,was performed to assess the neurogenesis in the dentate gyrus.We found that anti-CXCR7 antibody infusion enhanced the proliferation and dendritic development of doublecortin-labeled cells in the dentate gyrus in both ischemic and sham-operated rats.Spatial learning and memory functions were assessed by Morris water maze tests 30-32 days after ischemia.CXCR7-neutralizing antibody treatment significantly reduced the escape latency of the spatial navigation trial and increased the time spent in the target quadrant of spatial probe trial in animals that received ischemic insult,but not in sham operated rats.These results suggest that CXCR7-neutralizing antibody enhances the neurogenesis in the dentate gyrus and improves the cognitive function after cerebral ischemia in rats.All animal experimental protocols and procedures were approved by the Institutional Animal Care and Use Committee of China Medical University(CMU16089 R)on December 8,2016.

关键词： cerebral ischemia cognitive function CXCR7 dendritic development dentate gyrus doublecortin neurogenesis neutralizing antibody stroke stromal cell-derived factor-1

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N-methyl-D-aspartate receptor subunit 1 regulates neurogenesis in the hippocampal dentate gyrus of schizophrenia-like mice

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Neural Regeneration Research 2019年第12期14卷 2112-2117页

作者： Juan Ding Chun Zhang Yi-Wei Zhang Quan-Rui Ma Yin-Ming Liu Tao Sun Juan Liu Ningxia Key Laboratory of Cerebrocranial Diseases Institute of Basic Medical Sciences School of Basic Medical Sciences Ningxia Medical University

N-methyl-D-aspartate receptor hypofunction is the basis of pathophysiology in schizophrenia. Blocking the N-methyl-D-aspartate receptor impairs learning and memory abilities and induces pathological changes in the brain. Previous studies have paid little attention to the role of the N-methyl-D-aspartate receptor subunit 1 (NR1) in neurogenesis in the hippocampus of schizophrenia. A mouse model of schizophrenia was established by intraperitoneal injection of 0.6 mg/kg MK-801, once a day, for 14 days. In N-methyl-D-aspartate-treated mice, N-methyl-D-aspartate was administered by intracerebroventricular injection in schizophrenia mice on day 15. The number of NR1-, Ki67- or BrdU-immunoreactive cells in the dentate gyrus was measured by immunofluorescence staining. Our data showed the number of NR1-immunoreactive cells increased along with the decreasing numbers of BrdU- and Ki67-immunoreactive cells in the schizophrenia groups compared with the control group. N-methyl-D-aspartate could reverse the above changes. These results indicated that NR1 can regulate neurogenesis in the hippocampal dentate gyrus of schizophrenia mice, supporting NR1 as a promising therapeutic target in the treatment of schizophrenia. This study was approved by the Experimental Animal Ethics Committee of the Ningxia Medical University, China (approval No. 2014-014) on March 6, 2014.

关键词： nerve regeneration schizophrenia MK-801 N-methyl-D-aspartate neurogenesis N-methyl-D-aspartate receptor N-methyl-Daspartate receptor subunit 1 BrdU Ki67 hippocampal dentate gyrus hippocampal neurogenesis neural regeneration

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MicroRNA-132 in the Adult dentate Gyrus is Involved in Opioid Addiction Via Modifying the Differentiation of Neural Stem Cells

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Neuroscience Bulletin 2019年第3期35卷 486-496页

作者： Meng Jia Xuewei Wang Haolin Zhang Can Ye Hui Ma Mingda Yang Yijing Li Cailian Cui Department of Neurobiology School of Basic Medical Sciences Key Laboratory for Neuroscience of the Ministry of Education and National Health and Family Planning Commission Neuroscience Research Institute Peking University

MicroRNA-132(miR-132), a small RNA that regulates gene expression, is known to promote neurogenesis in the embryonic nervous system and adult brain.Although exposure to psychoactive substances can increase miR-132 expression in cultured neural stem cells(NSCs)and the adult brain of rodents, little is known about its role in opioid addiction. So, we set out to determine the effect of miR-132 on differentiation of the NSCs and whether this effect is involved in opioid addiction using the rat morphine self-administration(MSA) model. We found that miR-132 overexpression enhanced the differentiation of NSCs in vivo and in vitro. Similarly, speci?c overexpression of miR-132 in NSCs of the adult hippocampal dentate gyrus(DG) during the acquisition stage of MSA potentiated morphine-seeking behavior. These ?ndings indicate that miR-132 is involved in opioid addiction,probably by promoting the differentiation of NSCs in the adult DG.

关键词： miR-132 Opioid addiction Neural stem cell dentate gyrus

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Effects of electroacupuncture on the expressions of neuroal nitric oxide synthase and astrocyte in dentate gyrus of rats with Parkinson's disease

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China Medical Abstracts(Internal Medicine) 2013年第3期30卷 133-134页

作者：丁艳霞 Human Anatomy Teach & Res Sect Wannan Med Coll

Objective To observe the changes in the expression of neuroal nitric oxide synthase (nNOS) and glial fibrillary acidic protein (GFAP) in dentate gyrus (DG) of rats with Parkinson’s disease (PD) and effects of electro... 详细信息

关键词： dentate gyrus astrocyte nNOS fibrillary glial acidic puncture medial rotation

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The detrimental effects of lipopolysaccharideinduced neuroinflammation on adult hippocampal neurogenesis depend on the duration of the pro-inflammatory response

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Neural Regeneration Research 2019年第5期14卷 817-825页

作者： Martha Pérez-Domínguez Evangelina ávila-Mu?oz Eduardo Domínguez-Rivas Angélica Zepeda Departamento de Medicina Genómica y Toxicología Ambiental Instituto de Investigaciones Biomédicas.Universidad Nacional Autónoma de MéxicoCDMX

Adult hippocampal neurogenesis is a finely tuned process regulated by extrinsic factors. Neuroinflammation is a hallmark of several pathological conditions underlying dysregulation of neurogenesis. In animal models, lipopolysaccharide(LPS)-induced neuroinflammation leads to a neurogenic decrease mainly associated to the early inflammatory response. However, it is not well understood how the neuroinflammatory response progresses over time and if neurogenesis continues to be diminished during the late neuroinflammatory response. Moreover, it is unknown if repeated intermittent administration of LPS along time induces a greater reduction in neurogenesis. We administered one single intraperitoneal injection of LPS or saline or four repeated injections(one per week) of LPS or saline to young-adult mice. A cohort of new cells was labeled with three 5-bromo-2-deoxyuridine injections(one per day) 4 days after the last LPS injection. We evaluated systemic and neuroinflammation-associated parameters and compared the effects of the late neuroinflammatory response on neurogenesis induced by each protocol. Our results show that 1) a single LPS injection leads to a late pro-inflammatory response characterized by microglial activation, moderate astrocytic reaction and increased interleukin-6 levels. This response correlates in time with decreased neurogenesis and 2) a repeated intermittent injection of LPS does not elicit a late pro-inflammatory response although activated microglia persists. The latter profile is not accompanied by a continued longterm hippocampal neurogenic decrease. Hereby, we provide evidence that the neuroinflammatory response is a dynamic process that progresses in a milieu-dependent manner and does not necessarily lead to a neurogenic decrease, highlighting the complex interaction between the immune system and neurogenesis.

关键词： dentate gyrus subgranular zone inflammation microglia astrocytes IL-6 cytokines cell proliferation neural progenitor cells immature neurons long-term short-term adult hippocampal neurogenesis

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Optogenetics-induced activation of glutamate receptors improves memory function in mice with Alzheimer’s disease

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Neural Regeneration Research 2019年第12期14卷 2147-2155页

作者： Ke-Wei Wang Xiao-Lin Ye Ting Huang Xi-Fei Yang Liang-Yu Zou Department of Neurology Shenzhen People’s Hospital (First Affiliated Hospital of Southern University of Science and Technology) Second Clinical College Jinan University Shenzhen Guangdong Province China Key Laboratory of Modern Toxicology of Shenzhen Shenzhen Center for Disease Control and Prevention Shenzhen Guangdong Province China

Optogenetics is a combination of optics and genetics technology that can be used to activate or inhibit specific cells in tissues. It has been used to treat Parkinson’s disease, epilepsy and neurological diseases, but rarely Alzheimer’s disease. Adeno-associated virus carrying the CaMK promoter driving the optogenetic channelrhodopsin-2 (CHR2) gene (or without the CHR2 gene, as control) was injected into the bilateral dentate gyri, followed by repeated intrahippocampal injections of soluble low-molecular-weight amyloid-β1–42 peptide (Aβ1–42). Subsequently, the region was stimulated with a 473 nm laser (1–3 ms, 10 Hz, 5 minutes). The novel object recognition test was conducted to test memory function in mice. Immunohistochemical staining was performed to analyze the numbers of NeuN and synapsin Ia/b-positive cells in the hippocampus. Western blot assay was carried out to analyze the expression levels of glial fibrillary acidic protein, NeuN, synapsin Ia/b, metabotropic glutamate receptor-1a (mGluR-1a), mGluR-5, N-methyl-D-aspartate receptor subunit NR1, glutamate receptor 2, interleukin-1β, interleukin-6 and interleukin-10. Optogenetic stimulation improved working and short-term memory in mice with Alzheimer’s disease. This neuroprotective effect was associated with increased expression of NR1, glutamate receptor 2 and mGluR-5 in the hippocampus, and decreased expression of glial fibrillary acidic protein and interleukin-6. Our results show that optogenetics can be used to regulate the neuronal-glial network to ameliorate memory functions in mice with Alzheimer’s disease. The study was approved by the Animal Resources Committee of Jinan University, China (approval No. LL-KT-2011134) on February 28, 2011.

关键词： nerve regeneration Alzheimer's disease amyloid-β1-42 dentate gyrus channelrhodopsin-2 glutamate receptors memory neuroinflammation novel object recognition immunohistochemistry western blot assay neural regeneration

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Mental deficiency

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China Medical Abstracts(Internal Medicine) 2010年第3期27卷 190-191页

2010383 Longitudinal study of two subtypes of mild cognitive impairment. CHEN Meirong(陈美蓉),et al.Dept Neurol,Huashan Hosp,Fudan Univ,Shanghai 200040. Chin J Neurol 2010;43(5):351-352. Objective To investigate the conversion rate of subtypes of anmestic mild cognitive impairment (aMCI) to Alzheimer’s disease (AD) and assess the contribution

关键词： impairment Neurol hippocampal dentate gyrus hippocampus fibrillary rabbit labeling glial

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MECHANISM OF ACUPUNCTURE IN SUPPRESSING EPILEPTIC SEIZURES

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Journal of Traditional Chinese Medicine 1992年第3期12卷 187-192页

作者：吴定宗 Department of Physiology Shanghai College of Traditional Chinese MedicineShanghai 200032

Suppression of epileptic seizure byacupuncture was described early in the an-cient medical literature,and now this treat-ment is occasionally seen reported.The chiefadvantage of the acupuncture treatment isabsence of side-effects which antiepilepticdrugs usually have.Patients showing no re-sponse to drugs have been reported curedwhen treated by acupuncture.

关键词： seizure epileptic acupuncture occasionally Acupuncture minutes dentate showing sensory cortex

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