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Age-dependent neuron loss is associated with impaired adult neurogenesis in forebrain neuron-specific Dicer conditional knockout mice

Age-dependent neuron loss is associated with impaired adult ...

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第六届亚太神经科学联合会学术会议暨中国神经科学学会第十一届全国学术会议

作者： Shanshan Cheng Chen Zhang Congyu Xu Long Wang Xiaoxia Zou Guiquan Chen Model Animal Research Center MOE Key Laboratory of Model Animal for Disease StudyNanjing Biomedical Research InstituteNanjing University

Impairment in the micro RNA(mi RNA) network causes a number of neurodegenerative diseases. Endoribonuclease Dicer is a key RNase to produce mature mi RNAs. It has been shown that Dicer is important for the maintenance of excitatory neuron survival during early postnatal period. However, the role of Dicer in adult mature excitatory neuron survival is not clear. In this study, we generated a mouse model in which Dicer is conditionally inactivated in forebrain excitatory neurons from a mature stage, and this line is termed Dicer conditional knockout(c KO). Significant age-dependent neurodegeneration was observed in the cortex of Dicer c KO mice, indicating an important role of Dicer in the maintenance of mature excitatory neuron survival in the adult cortex. Impairment in adult neurogenesis was found in 6-month but not in young Dicer c KO mice. However, astrocytosis was detected in young Dicer c KO mice displaying no apparent neuron loss. Overall, neurogenesis impairment and neuroinflammation may play pivotal roles in the progression of neurodegeneration.

关键词： Neuron loss Mouse model miRNA Dicer Neuronal survival

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Thalamus-habenula pathway controls light-dark preference behavior in zebrafish larvae

Thalamus-habenula pathway controls light-dark preference beh...

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第六届亚太神经科学联合会学术会议暨中国神经科学学会第十一届全国学术会议

作者： Bai-bing Zhang Yuan-yuan Yao Jiu-lin Du Institute of Neuroscience State Key Laboratory of NeuroscienceCenter for Excellence in Brain ScienceShanghai Institutes for Biological SciencesChinese Academy of Sciences Graduate School University of Chinese Academy of Sciences School of Life Science and Technology Shanghai Tech University

Appropriate preference for light or dark is crucial for animal's survival, but the underlying circuit mechanism is largely unknown. Here, by combining behavioral assay, in vivo optoand electro-physiological recording, optogenetic manipulation and morphological tracing in zebrafish larvae, we demonstrated that a circuitry consisted of retinal ganglion cells(RGCs), thalamus and left dorsal habenula(ld Hb) mediates the light-dark preference. Lesion or dysfunction of RGCs, thalamus or ld Hb diminished light preference, while optogenetic activation of the habenula recovered light preference of larvae with removal of both eyes. At anatomical level, a sub-region of the thalamus locating at the arborization field 4(AF4) of RGCs receives direct RGC innervation. Thalamic neurons at this region send projections to the ld Hb directly and form functional synapses with ld Hb neurons. Thus, our study identifies a neural circuitry which mediates light-dark preference behavior in vertebrates.

关键词： light-dark preference,thalamus,habenula,zebrafish

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Effects of Exhaustive Treadmill Running on Synaptic Ultrastructure in Dorsolateral Striatum of Rat

Effects of Exhaustive Treadmill Running on Synaptic Ultrastr...

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第六届亚太神经科学联合会学术会议暨中国神经科学学会第十一届全国学术会议

作者： Jiali Cheng Lijuan Hou Xiaoli Liu Decai Qiao Exercise Physiology Lab Beijing Normal University

Background: The striatum is a major component of the basal ganglia and is associated with motor and cognitive functions. Neurons projecting from the striatum receive a large convergence of afferents from all areas of the cortex,which has a crucial integrative and computational role, leading to the acquisition *** this work, the synapticultrastructure variations in dorsolateral striatum(DLS) of rat is investigated to discuss central nervous system role of exercise fatigue. Methods: Male SD rats were randomly divided into a control group(CG) and fatigue group(FG).We selecttreadmill incremental exercise program to establish exercise-induced fatigue model. The transmission electron microscope(TEM) is detected to synaptic ultrastructure in dorsolateral ***:(1) Synaptic vesicle amount in DLS was significantly increased in FG(p<0.05).(2) Thickness of post-synaptic density(PSD) increased in FG(p<0.05), and the width ofsynaptic cleft is remarkably decreased in FG(p<0.05).(3) The amount of mitochondria locatinginpresynaptic is decreased in FG(p<0.05).Conclusions: This study demonstrate that exhaustive exercise result in the synaptic ultrastructure variations in dorsolateral striatum. It suggests that DLS plays an important role in synaptic plasticity during exercise fatigue.(31171138/31401018)(5142012).

关键词： exhaustive exercise synaptic ultrastructure dorsolateral striatum

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Resting state fMRI and viral neuronal tracing in the FMR1 gene knockout rat model

Resting state fMRI and viral neuronal tracing in the FMR1 ge...

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第六届亚太神经科学联合会学术会议暨中国神经科学学会第十一届全国学术会议

作者： Yue Liu Fu-Qiang Xu Wuhan National Laboratory for Optoelectronics Huazhong university of science and technology

Objective FMR1(fragile X mental retardation 1) is a gene that codes for a protein called fragile X mental retardation protein, or FMRP. This protein, most commonly found in the brain, is essential for normal cognitive development. We try to investigate the influences on brain function and relevant neural circuits induced by FMR1 gene. Methods Using resting state(RS) functional magnetic resonance imaging(f MRI), the connectivity patterns of cognitive relevant brain regions were explored in FMR1 rat models and wild type controls. Neuronal tracing with HSV(Herpes Simplex virus) and Pr V(Pseudorabies) were also used for demonstrating the structure connectivity in some of these brain areas. Results(1) We found that some regions like the CA2 region of hippocampus appeared an obviously decrease of interhemispheric functional connectivity.(2)The viral neural circuit results also supported the phenomenon by the abnormal structure connectivity. Conclusion FMR1 gene deletion may lead to an unusual connectivity of hemispheres.

关键词： Fmr1 gene resting state fMRI neural tracing HSV PrV

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Anterior auditory cortex strengthened sound selectivity via cortical computation

Anterior auditory cortex strengthened sound selectivity via ...

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第六届亚太神经科学联合会学术会议暨中国神经科学学会第十一届全国学术会议

作者： Can Tao Guang-Wei Zhang Chang Zhou Su-Mei Yan Li-Juan Wang Yi Zhou Ying Xiong Department of Neurobiology Chongqing Key Laboratory of NeurobiologyThird Military Medical University

Anterior auditory field(AAF) and primary auditory cortex(A1) constitute the core region of auditory cortex yet how the information been coded in AAF remained to be elucidated. The present work is to functionally localize AAF and study its evoked responses by sound stimulation. Multi-unit extracellular recording was applied to obtain the frequency gradient of AAF. In vivo loose-patch was performed to study the evoked single neuron activity and synaptic responses were acquired by in vivo whole-cell recording. AAF is rostral and ventral to AI and has a mirror frequency gradient with A1. Robust tonal evoked responses could be observed in 30% recorded excitatory neurons in AAF and they are highly selective to both sound frequency and intensity. In vivo voltage-clamp recording revealed that temporal profile and frequency tuning of tonal evoked excitation and inhibition is different. The evoked excitatory postsynaptic current(EPSC) showed a long duration compared with inhibitory postsynaptic current(IPSC), this suggest that complex cortical computation is involved. Our results suggested that cortical computation in AAF strengthened the sound selectivity.

关键词： anterior auditory cortex tonal receptive field in vivo patch clamp

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The Method of Attaining high transfection efficiency of plasmid into neural stem cells by electroporator

The Method of Attaining high transfection efficiency of plas...

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第六届亚太神经科学联合会学术会议暨中国神经科学学会第十一届全国学术会议

作者： Xiaohua Jiang Jingrui Tian Yanxia Tian Junling Gao School of Basic Medicine Hebei Key Lab For Chronic DiseasesNorth China University of Science and Technolgy

Objective: To optimize the conditions of transfecting eukaryotic expression vector p EGFP-N1 into neural stem cells(NSCs) from rat's by CUY21 EDITII electroporator, in order to improve the transfection efficiency of exogenous gene into NSCs and provide a basis for the follow-up experiments. Methods: Using different PpV, but same Pd V, pulse time and cycle time, pE GFP-N1 which expresses green fluorescence protein(GFP) was transfected into NSCs by CUY21 EDITII electroporator. Then the transfection efficiency was calculated by counting the NSCs with green fluorescent at 48 h after transfection. Results: The satisfactory transfection efficiency was acquired under the condition of PpV(350 V), Pd V(20 V), pulse time(10 ms), number of cycles(20). The average transfection rates of electroporation was 81.0% and the survival rate was 72.0%. Conclusion: The high transfection rate could be acquired by optimizing the transfection conditions. It suggested that electroporation by CUY21EDITⅡelectroporator was a more efficient method for plasmid into NSCs than lipofectamine.

关键词： neural stem cells electroporation lipofectamine transfection

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Endosomal adaptor protein APPL1,a new player in signaling from synapse to nucleus

Endosomal adaptor protein APPL1,a new player in signaling fr...

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第六届亚太神经科学联合会学术会议暨中国神经科学学会第十一届全国学术会议

作者： Yu Wu Yinggang Yan Xinyou Lv Changwan Chen JieJie Wang Jianhong Luo Shuang Qiu Department of Neurobiology Key Laboratory of Medical Neurobiology of the Ministry of Health of ChinaZhejiang University School of Medicine

Activity-dependent modification of gene expression is a powerful means by which the neurons builds up long-term modification. Local signaling events at synapses or axon terminals are communicated to the nucleus to elicit transcriptional responses, and thereby translates information about the external environment into internal neuronal representations. This retrograde signaling is critical to dendritic growth, synapse development, and neuronal plasticity. However, the lengths of neuronal processes pose a significant challenge for such intracellular communications. Here, we found that synaptic activity induced nuclear translocation of an endosomal adaptor protein APPL1 in the excitatory neurons. Nuclear translocation of APPL1 requires calcium influx from NMDA receptors or L-type VGCC. Futhermore, a peptide against the NLS of APPL1 blocked synaptic activity-dependent nuclear translocation of APPL1, as well as the upregulation of CREB phosphorylation at Ser133 site in the nucleus. These data indicate that APPL1 is a key player transducing signals from synapse to nucleus and modulating gene transcription.

关键词： appl1,nuclear translocation,gene expression,synaptic activity

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Minocycline reduces neuroinflammation but does not ameliorate neuron loss in a mouse model of neurodegeneration

Minocycline reduces neuroinflammation but does not ameliorat...

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第六届亚太神经科学联合会学术会议暨中国神经科学学会第十一届全国学术会议

作者： Shanshan Cheng Jinxing Hou Chen Zhang Congyu Xu Long Wang Xiaoxia Zou Huahong Yu Yun Shi Zhenyu Yin Guiquan Chen Model Animal Research Center MOE Key Laboratory of Model Animal for Disease StudyNanjing University School of Life Sciences Nanchang University Department of Geriatric Nanjing Drum Tower HospitalNanjing University Medical School

Minocycline is a broad-spectrum tetracycline antibiotic. A number of preclinical studies have shown that minocycline exhibits neuroprotective effects in various animal models of neurological diseases. However, it remained unknown whether minocycline is effective to prevent neuron loss. To systematically evaluate its effects, minocycline was used to treat Dicerconditional knockout(cKO) mice which display age-related neuron loss. The drug was given to mutant mice prior to the occurrence of neuroinflammation and neurodegeneration, and the treatment had lasted 2 months. Levels of inflammation markers, including glial fibrillary acidic protein(GFAP), ionized calciumbinding adapter molecule1(Iba1) and interleukin6(IL6), were significantly reduced in minocyclinetreated DicercKO mice. In contrast, levels of neuronal markers and the total number of apoptotic cells in DicercKO mice were not affected by the drug. In summary, inhibition of neuroinflammation by minocycline is insufficient to prevent neuron loss and apoptosis.

关键词： neuroinflammation neurodegeneration minocycline,Dicer

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Dissecting multi-layer mechanisms regulating neural stem cell development in the cerebral cortex

Dissecting multi-layer mechanisms regulating neural stem cel...

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第六届亚太神经科学联合会学术会议暨中国神经科学学会第十一届全国学术会议

作者： Qin Shen Center for Stem Cell Biology and Regenerative Medicine School of MedicineTsinghua-Peking Center for Life SciencesTsinghua University

Neural stem cells(NSCs) are the founding cells of the central nervous system, generating a large variety of neurons and glia during embryonic development. NSCs exist in the ventricular zone and subventricular zone of the developing brain and persist into the adulthood in specialized niches: the subventricular zone lining the lateral side of the lateral ventricle and the dentate gyrus of hippocampus. NSCs produce new neurons throughout life, a process called neurogenesis, to build up the complex brain circuitry during development and to participate in learning and memory function in the adult. Our previous studies have helped understand the progressive changes in lineage pattern and fate potential of NSCs and characterized the interactions between NSCs and stem cell niche components. Using a combination of in vitro and in vivo approaches, we are further investigating the molecular mechanisms regulating the development of NSCs in the developing cerebral cortex, from both intrinsic and extrinsic aspects. Our basic understanding of neural stem cell biology will allow us to evaluate changes in neural stem cell behavior in response to pathological insults, and to explore the therapeutic potential to use neural stem cells as a diagnostic and repairing tool for neurological disorders.

关键词： neural stem cells,cerebral cortex,lineage,stem cell niche

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The protective effect of ischemic post-conditioning against stroke in rat

The protective effect of ischemic post-conditioning against ...

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第六届亚太神经科学联合会学术会议暨中国神经科学学会第十一届全国学术会议

作者： Kezhou Liu Xiabing Yuan Yawei Tu Ming Yan Yong Yang College of Life Information Science and Instrument Engineering Hangzhou Dianzi University

Ischemic post-conditioning(IPC), a concept derived from myocardial ischemic models, confers neuroprotection in various models of experimental stroke. Transient mechanical interruption of reperfusion induces IPC which can attenuate reperfusion injury. In this study, we compared the protective effects of two postconditioning conditions with different numbers of cycles for reperfusion/occlusion. Rats were randomly assigned to 4 groups, consisting of sham, control ischemia, postconditioning with two conditions. We used middle cerebral artery occlusion(MCAo) model and detected the cerebral blood flow(CBF) during IPC to make sure the ischmia and IPC happen. Behavior test, TTC, HE stain were chosen to evaluate the protective effects of different IPCs. We found that IPC indeed had the protective effect against stroke and the effect of 3 cycles of same period reperfusion/occlusion was better than 10 cycles. We hypothesized that the first 3 cycles of reperfusion/occlusion was crucial to the IPC neuroprotection. Too many cycles could influence the normal reperfusion and attenuate the IPC protective effec.

关键词： ischemic post-conditioning,stroke,protective effect

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