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Epigenomic landscapes during prefrontal cortex development and aging in rhesus

National Science Review 2024年第8期11卷 75-97页

作者： Chao Ning Xi Wu Xudong Zhao Zongyang Lu Xuelong Yao Tao Zhou Lizhi Yi Yaoyu Sun Shuaishuai Wu Zhenbo Liu Xingxu Huang Lei Gao Jiang Liu National Laboratory of Biomacromolecules CAS Center for Excellence in BiomacromoleculesInstitute of Biophysics Chinese Academy of Sciences College of Life Sciences University of Chinese Academy of Sciences Division of HIV/AIDS and Sex-Transmitted Virus Vaccines Institute for Biological Product ControlNational Institutes for Food and Drug Control(NIFDC) State Key Laboratory of Drug Regulatory Science Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences Kunming Institute of ZoologyChinese Academy of Sciences School of Life Science and Technology Shanghai Tech University Guangzhou Nvwa Life Technology Co. Ltd Shenzhen Neher Neural Plasticity Laboratory CAS Key Laboratory of Brain Connectome and Manipulation The Brain Cognition and Brain Disease Institute Shenzhen Institute of Advanced Technology Chinese Academy of Sciences Key Laboratory of Epigenetic Regulation and Intervention Institute of Biophysics Chinese Academy of Sciences Zhejiang Provincial Key Laboratory of Pancreatic Disease The First Affiliated Hospital and Institute of Translational Medicine Zhejiang University School of Medicine Center for Excellence in Animal Evolution and Genetics Chinese Academy of Sciences

The prefrontal cortex(PFC) is essential for higher-level cognitive *** epigenetic dynamics participates in PFC development and aging is ***,we profiled epigenomic landscapes of rhesus monkey PFCs from prenatal to aging *** dynamics of chromatin states,including higher-order chromatin structure,chromatin interaction and histone modifications are coordinated to regulate stage-specific gene transcription,participating in distinct processes of *** changes of epigenetic signals occur around the birth ***,genes involved in neuronal cell differentiation and layer specification are pre-configured by bivalent *** identified a cis-regulatory module and the transcription factors(TFs) associated with basal radial glia development,which was associated with large brain size in *** TFs include GLI3,CREB5 and ***,the genes associated with the basal radial glia(bRG)-associated cis-element module,such as SRY and SOX9,are enriched in sex ***-associated single nucleotide polymorphisms are more enriched in super enhancers(SEs) than typical enhancers,suggesting that SEs play an important role in neural network wiring.A cis-regulatory element of DBN1 is identified,which is critical for neuronal cell proliferation and synaptic neuron ***,the loss of distal chromatin interaction and H3K27me3 signal are hallmarks of PFC aging,which are associated with abnormal expression of aging-related genes and transposon activation,***,our findings shed light on epigenetic mechanisms underlying primate brain development and aging.

关键词： rhesus macaque prefrontal cortex 3D genomics chromatin immunoprecipitation sequencing development aging

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Dopamine in the prefrontal cortex plays multiple roles in the executive function of patients with Parkinson's disease

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Neural Regeneration Research 2024年第8期19卷 1759-1767页

作者： Zihang Zhou Yalong Yan Heng Gu Ruiao Sun Zihan Liao Ke Xue Chuanxi Tang Department of Neurobiology Xuzhou Key Laboratory of NeurobiologyXuzhou Medical UniversityXuzhouJiangsu ProvinceChina

Parkinson’s disease can affect not only motor functions but also cognitive abilities,leading to cognitive *** common issue in Parkinson’s disease with cognitive dysfunction is the difficulty in executive *** functions help us plan,organize,and control our actions based on our *** brain area responsible for executive functions is called the prefrontal co *** acts as the command center for the brain,especially when it comes to regulating executive *** role of the prefrontal cortex in cognitive processes is influenced by a chemical messenger called ***,little is known about how dopamine affects the cognitive functions of patients with Parkinson’s *** this article,the authors review the latest research on this *** start by looking at how the dopaminergic syste m,is alte red in Parkinson’s disease with executive ***,they explore how these changes in dopamine impact the synaptic structure,electrical activity,and connection components of the prefrontal *** authors also summarize the relationship between Parkinson’s disease and dopamine-related cognitive *** information may offer valuable insights and directions for further research and improvement in the clinical treatment of cognitive impairment in Parkinson’s disease.

关键词： dopamine dopamine receptor dopamine transporter executive dysfunction neural network neural oscillation prefrontal cortex synaptic plasticity

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A Context-Based Analgesia Model in Rats: Involvement of prefrontal cortex

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Neuroscience Bulletin 2018年第6期34卷 1047-1057页

作者： Lingchi Xu Yalan Wan Longyu Ma Jie Zheng Bingxuan Han Feng-Yu Liu Ming Yi You Wan Neuroscience Research Institute Peking University Department of Clinical Medicine Zhongshan School of Medicine Sun Yat-Sen University Department of Neurobiology School of Basic Medical Sciences Peking University Key Laboratory for Neuroscience Ministry of Education/National Health and Family Planning Commission Peking University Co-innovation Center of Neuroregeneration Nantong University

Cognition and pain share common neural substrates and interact reciprocally: chronic pain compromises cognitive performance, whereas cognitive processes modulate pain perception. In the present study, we established a non-drug-dependent rat model of context-based analgesia,where two different contexts(dark and bright) were matched with a high(52°C) or low(48°C) temperature in the hot-plate test during training. Before and after training,we set the temperature to the high level in both *** showed longer paw licking latencies in trials with the context originally matched to a low temperature than those to a high temperature, indicating successful establishment of a context-based analgesic effect in rats. This effect was blocked by intraperitoneal injection of naloxone(an opioid receptor antagonist) before the probe. The context-based analgesic effect also disappeared after optogenetic activation or inhibition of the bilateral infralimbic or prelimbic sub-region of the prefrontal cortex. In brief, we established a context-based, non-drug dependent, placebo-like analgesia model in the rat. This model provides a new and useful tool for investigating the cognitive modulation of pain.

关键词： Context-based analgesia Placebo analgesia Pain Hot-plate test Cognition modulation Opioid system prefrontal cortex

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Wake-promoting effects of vagus nerve stimulation after traumatic brain injury: upregulation of orexin-A and orexin receptor type 1 expression in the prefrontal cortex

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Neural Regeneration Research 2018年第2期13卷 244-251页

作者： Xiao-yang Dong Zhen Feng Department of Rehabilitation Medicine the First Affiliated Hospital of Nanchang University

Orexins, produced in the lateral hypothalamus, are important neuropeptides that participate in the sleep/wake cycle, and their expres- sion coincides with the projection area of the vagus nerve in the brain. Vagus nerve stimulation has been shown to decrease the amounts of daytime sleep and rapid eye movement in epilepsy patients with traumatic brain injury. In the present study, we investigated whether vagus nerve stimulation promotes wakefulness and affects orexin expression. A rat model of traumatic brain injury was established using the free fall drop method. In the stimulated group, rats with traumatic brain injury received vagus nerve stimulation （frequency, 30 Hz, current, 1.0 mA; pulse width, 0.5 ms; total stimulation time, 15 minutes）. In the antagonist group, rats with traumatic brain injury were intracerebroventricularly injected with the orexin receptor type 1 （OXIR） antagonist SB334867 and received vagus nerve stimulation. Changes in consciousness were observed after stimulation in each group. Enzyme-linked immunosorbent assay, western blot assay and immunohistochemistry were used to assess the levels of orexin-A and OX1R expression in the prefrontal cortex. In the stimulated group, consciousness was substantially improved, orexin-A protein expression gradually increased within 24 hours after injury and OX1R expres- sion reached a peak at 12 hours, compared with rats subjected to traumatic brain injury only. In the antagonist group, the wake-promoting effect of vagus nerve stimulation was diminished, and orexin-A and OX1R expression were decreased, compared with that of the stim- ulated group. Taken together, our findings suggest that vagus nerve stimulation promotes the recovery of consciousness in comatose rats after traumatic brain injury. The upregulation of orexin-A and OXIR expression in the prefrontal cortex might be involved in the wake-promoting effects of vagus nerve stimulation.

关键词： nerve regeneration brain injury orexin-A orexin receptor type 1 vagus nerve stimulation traumatic brain injury wake-promoting coma wakefulness prefrontal cortex neurotransmitter neural regeneration

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Olanzapine Induces Inflammation and Immune Response via Activating ER Stress in the Rat prefrontal cortex

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Current Medical Science 2021年第4期41卷 788-802页

作者： Wen-ting LI Xu-feng HUANG Chao DENG Bao-hua ZHANG Kun QIAN Meng HE Tao-lei SUN School of Chemistry Chemical Engineering and Life SciencesWuhan University of TechnologyWuhan 430070China Illawarra Health and Medical Research Institute and Centre for Translational Neuroscience School of MedicineUniversity of WollongongNSW 2522Australia The National Clinical Research Center for Mental Disorders&Beijing Key Laboratory of Mental Disorders Beijing Anding Hospital&the Advanced Innovation Center for Human Brain ProtectionCapital Medical UniversityBeijing 100069China

Objective Antipsychotics,in particular olanzapine,are first-line medications for *** prefrontal cortex(PFC)is an important region for antipsychotics’therapeutic *** PFC inflammatory and immune pathways are associated with schizophrenia ***,the effect of antipsychotics on the inflammatory and immune pathways in the PFC remains *** aimed to examined the time-dependent effect of olanzapine on inflammatory and immune markers in the PFC of *** the inflammatory and immune pathways are related to endoplasmic reticulum(ER)stress,we further investigated whether or not olanzapine-induced inflammation and immune responses were related to ER *** Expression of pro-inflammatory markers including IkappaB kinaseβ(IKKβ),nuclear factor kappa B(NFκB),tumor necrosis factorα(TNF-α),interleukin-6(IL-6)and IL-1β,and immune-related proteins including inducible nitric oxide synthase(iNOS),toll-like receptor 2(TLR2)and cluster of differentiation 14(CD14)were examined by Western *** Olanzapine treatments for 1,8 and 36 days significantly activated the inflammatory IKKβ/NFκB signaling,and increased the expression of TNF-α,IL-6,IL-1βand immune-related proteins such as iNOS,TLR4 and *** treatment for 1 day,8 and 36 days also induced ER stress in the ***-treatment with an ER stress inhibitor,4-phenylbutyrate,inhibited olanzapine-induced inflammation and the immune response in the *** These results suggested olanzapine exposure could be a factor that induces central inflammation and immunological abnormities in schizophrenia *** induces PFC inflammation and immune response,possibly via activating ER stress signaling.

关键词： olanzapine prefrontal cortex inflammation immune response endoplasmic reticulum stress

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Chlorogenic acid ameliorates chronic stress-induced prefrontal cortex injury through activating the 5-HT/BDNF signaling pathway in rats

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Food Bioscience 2022年第6期50卷 1794-1804页

作者： Shuping Zhao Tianyuan Yang Xiaoyu Hou Haiyang Zhang Yuan Zhao Hui Wang Ning Sun Haoyang Tan Jiuyan Zhang Honggang Fan Heilongjiang Key Laboratory for Laboratory Animals and Comparative Medicine College of Veterinary MedicineNortheast Agricultural UniversityHarbinChina College of Veterinary Medicine South China Agricultural UniversityGuangzhou510642China

The chlorogenic acid(CGA)has a strong neuroprotective ability and cognitive *** purpose of this study was to investigate the effect and mechanism of CGA on chronic restraint stress(CRS)-induced prefrontal cortex(PFC)injury and depression-like *** were restrained for 6 h each day to create a CRS paradigm that lasted for 21 *** hour prior to constraint,CGA(50 mg/kg,100 mg/kg and 150 mg/kg)was intragastrically *** results showed that CGA could reduce serum corticosterone(CORT)levels in rats and 100 mg/kg CGA could prevent CRS-induced depression-like *** revealed that 100 mg/kg CGA ameliorated CRS-induced PFC ***,5-HT content was also ***,100 mg/kg of CGA will be used to further probe the molecular mechanism of regulating *** using transmission electron microscopy demonstrated that CGA reduced CRS-induced PFC synaptic *** promotes cAMP-CREB-BDNF signaling pathway and inhibits indoleamine 2,3-dioxygenase(IDO)and serotonin transporter(SRET).Cellular thermal shift assays(CETSA)and molecular docking studies have shown that IDO,SERT and CGA docking have priority potential ***,a protective effect of CGA is seen in rats with CRS-induced PFC by regulating the expression of IDO and SERT and then affecting the effect of 5-HT on the cAMP-CREB-BDNF signaling pathway.

关键词： Chlorogenic acid Chronic stress prefrontal cortex Depression-like behavior 5-HT

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prefrontal cortex and the dysconnectivity hypothesis of schizophrenia

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Neuroscience Bulletin 2015年第2期31卷 207-219页

作者： Yuan Zhou Lingzhong Fan Chenxiang Qiu Tianzi Jiang Key Laboratory of Behavioral Science Institute of Psychology Chinese Academy of Sciences Magnetic Resonance Imaging Research Center Institute of Psychology Chinese Academy of Sciences Brainnetome Center Institute of Automation Chinese Academy of Sciences National Laboratory of Pattern Recognition Institute of Automation Chinese Academy of Sciences The Queensland Brain Institute The University of Queensland Key Laboratory for Neuro Information of the Ministry of Education School of Life Science and Technology University of Electronic Science and Technology of China

Schizophrenia is hypothesized to arise from disrupted brain connectivity. This ＂dysconnectivity hypothesis＂ has generated interest in discovering whether there is anatomical and functional dysconnectivity between the prefrontal cortex （PFC） and other brain regions, and how this dysconnectivity is linked to the impaired cognitive functions and aberrant behaviors of schizophrenia. Critical advances in neuroimaging technologies, including diffusion tensor imaging （DTI） and functional magnetic resonance imaging （fMRI）, make it possible to explore these issues. DTI affords the possibility to explore anatomical connectivity in the human brain in vivo and fMRI can be used to make inferences about functional connections between brain regions. In this review, we present major advances in the understanding of PFC anatomical and functional dysconnectivity and their implications in schizophrenia. We then briefly discuss future prospects that need to be explored in order to move beyond simple mapping of connectivity changes to elucidate the neuronal mechanisms underlying schizophrenia.

关键词： prefrontal cortex schizophrenia anatomical connectivity functional connectivity

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prefrontal cortex and sensory cortices during working memory: quantity and quality

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Neuroscience Bulletin 2015年第2期31卷 175-182页

作者： Yixuan Ku Mark Bodner Yong-Di Zhou Key Laboratory of Brain Functional Genomics Ministry of Education Shanghai Key Laboratory of Brain Functional Genomics Institute of Cognitive Neuroscience School of Psychology and Cognitive Science East China Normal University MIND Research Institute Department of Neurosurgery Johns Hopkins University NYU-ECNU Institute of Brain and Cognitive Science at NYU Shanghai

The activity in sensory cortices and the prefrontal cortex （PFC） throughout the delay interval of working memory （WM） tasks reflect two aspects of WM-quality and quantity, respectively. The delay activity in sensory cortices is fine-tuned to sensory information and forms the neural basis of the precision of WM storage, while the delay activity in the PFC appears to represent behavioral goals and filters out irrelevant distractions, forming the neural basis of the quantity of task-relevant information in WM. The PFC and sensory cortices interact through different frequency bands of neuronal oscillation （theta, alpha, and gamma） to fulfill goal-directed behaviors.

关键词： working memory prefrontal cortex capacity limit memory precision neuronal oscillations

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Atrophy of the left dorsolateral prefrontal cortex is associated with poor performance in verbal fluency in elderly poststroke women

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Neural Regeneration Research 2013年第4期8卷 346-356页

作者： Yang-Kun Chen Wei-Min Xiao Defeng Wang Lin Shi Winnie CW Chu Vincent CT Mok Ka Sing Wong Gabor S Ungvari Wai Kwong Tang Department of Neurology Dongguan People's Hospital Department of Diagnostic Radiology and Organ Imaging the Chinese University of Hong Kong Department of Medicine and Therapeutics the Chinese University of Hong Kong Graylands Hospital School of Psychiatry & Clinical NeurosciencesUniversity of Western AustraliaPerth 6005Australia Department of Psychiatry the Chinese University of Hong Kong

This study aimed to investigate the association between atrophy in the prefrontal cortex with executive function and verbal fluency in elderly male and female patients poststroke. Thirty elderly female patients with non-aphasic ischemic stroke aged -〉 60 years and 30 age-matched non-aphasic male patients with ischemic stroke were recruited. Automatic magnetic resonance imaging segmentation was used to assess the volume of the whole prefrontal cortex, along with its subdivisions： anterior cingulate cortex, orbitofrontal cortex and dorsolateral prefrontal cortex. The Semantic Verbal Fluency Test was administered at 3 and 15 months poststroke. At 3 months poststroke, left dorsolateral prefrontal cortex volume was significantly correlated with Verbal Fluency Test score in female patients only （partial coefficient = 0.453, P = 0.045）, after controlling for age, education, diabetes, neurological deficit, white matter lesions volume, as well as the location and volume of infarcts. At 15 months poststroke, there remained a significant association between the left dorsolateral prefrontal cortex volume and Verbal Fluency Test （partial coefficient = 0.661, P = 0.001） and between the left prefrontal cortex volume and Verbal Fluency Test （partial coefficient = 0.573, P = 0.004） in female patients after the same adjustments. These findings indicate that atrophy of the left dorsolateral prefrontal cortex contributes to the impairment of verbal fluency in elderly female patients with stroke. Sex differences may be present in the neuropsychological mechanisms of verbal fluency impairment in patients with stroke.

关键词： neural regeneration neuroimaging brain atrophy verbal fluency executive function stroke sex differences prefrontal cortex dorsolateral prefrontal cortex magnetic resonance imaging grants-supported paper photographs-containing paper neuroregeneration

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The long rather than the short allele of 5-HTTLPR predisposes Han Chinese to anxiety and reduced connectivity between prefrontal cortex and amygdala

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Neuroscience Bulletin 2013年第1期29卷 4-15页

作者： Haixia Long Bing Liu Bing Hou Chao Wang Jin Li Wen Qin Dawei Wang Yuan Zhou Keith M. Kendrick Chunshui Yu Tianzi Jiang LIAMA Center for Computational Medicine National Laboratory of Pattern Recognition Institute of Automation Chinese Academy of Sciences Key Laboratory for NeuroInformation of the Ministry of Education School of Life Science and Technology University of Electronic Science and Technology of China Department of Radiology Tianjin Medical University General Hospital Key Laboratory of Behavioral Science Institute of Psychology Chinese Academy of Sciences Queensland Brain Institute University of Queensland Brisbane QLD 4072 Australia

The short allele of the serotonin-transporter gene is associated with higher risk for anxiety and depression in Caucasians, but this association is still unclear in Asians. Here, we addressed this issue using behavioral and multi-modal MRI approaches in a large group of healthy Han Chinese participants （n = 233）. In contrast to findings in Caucasians, we found that long-allele （L） carriers had higher anxiety scores. In another group （n = 64） experiencing significant levels of depression or anxiety, the L-allele frequency was also significantly higher. In healthy participants, L-carriers had reduced functional and anatomical connectivity between the amygdala and prefrontal cortex （PFC）, which was correlated with anxiety or depression scores. Our findings demonstrated that in Chinese Han participants, in contrast to Caucasians, the L-allele confers vulnerability to anxiety or depression and weakens top-down emotional control between the PFC and amygdala. Therefore, ethnic background should be taken into account in gene-related studies and their potential clinical applications.

关键词： 5-HTTLPR functional and anatomical connectivity amygdala prefrontal cortex Han Chinese

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