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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 impairment.One common issue in Parkinson’s disease with cognitive dysfunction is the difficulty in executive functioning.Executive functions help us plan,organize,and control our actions based on our goals.The brain area responsible for executive functions is called the prefrontal co rtex.It acts as the command center for the brain,especially when it comes to regulating executive functions.The role of the prefrontal cortex in cognitive processes is influenced by a chemical messenger called dopamine.However,little is known about how dopamine affects the cognitive functions of patients with Parkinson’s disease.In this article,the authors review the latest research on this topic.They start by looking at how the dopaminergic syste m,is alte red in Parkinson’s disease with executive dysfunction.Then,they explore how these changes in dopamine impact the synaptic structure,electrical activity,and connection components of the prefrontal cortex.The authors also summarize the relationship between Parkinson’s disease and dopamine-related cognitive issues.This 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

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

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

Melatonin improves synapse development by PI3K/Akt signaling in a mouse model of autism spectrum disorder

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Neural Regeneration Research 2024年第7期19卷 1618-1624页

作者： Luyi Wang Man Xu Yan Wang Feifei Wang Jing Deng Xiaoya Wang Yu Zhao Ailing Liao Feng Yang Shali Wang Yingbo Li Institute of Neuroscience Department of PhysiologySchool of Basic Medical ScienceChongqing Medical UniversityChongqingChina Department of Pediatric Chongqing University Fuling HospitalChongqingChina Department of Neurosurgery Xinqiao HospitalArmy Medical UniversityChongqingChina Department of Pathology Affiliated Hospital of North Sichuan Medical CollegeNanchongSichuan ProvinceChina NHC Key Laboratory of Birth Defects and Reproductive Health Chongqing Population and Family Planning Science and Technology Research InstituteChongqingChina China National Clinical Research Center for Neurological Diseases Beijing Tiantan HospitalCapital Medical UniversityBeijingChina Advanced Innovation Center for Human Brain Protection Capital Medical UniversityBeijingChina

Autism spectrum disorders are a group of neurodevelopmental disorders involving more than 1100 genes,including Ctnnd2 as a candidate gene.Ctnnd2knockout mice,serving as an animal model of autis m,have been demonstrated to exhibit decreased density of dendritic spines.The role of melatonin,as a neuro hormone capable of effectively alleviating social interaction deficits and regulating the development of dendritic spines,in Ctnnd2 deletion-induced nerve injury remains unclea r.In the present study,we discove red that the deletion of exon 2 of the Ctnnd2 gene was linked to social interaction deficits,spine loss,impaired inhibitory neurons,and suppressed phosphatidylinositol-3-kinase(PI3K)/protein kinase B(Akt) signal pathway in the prefrontal cortex.Our findings demonstrated that the long-term oral administration of melatonin for 28 days effectively alleviated the aforementioned abnormalities in Ctnnd2 gene-knockout mice.Furthermore,the administration of melatonin in the prefro ntal cortex was found to improve synaptic function and activate the PI3K/Akt signal pathway in this region.The pharmacological blockade of the PI3K/Akt signal pathway with a PI3K/Akt inhibitor,wo rtmannin,and melatonin receptor antagonists,luzindole and 4-phenyl-2-propionamidotetralin,prevented the melatonin-induced enhancement of GABAergic synaptic function.These findings suggest that melatonin treatment can ameliorate GABAe rgic synaptic function by activating the PI3K/Akt signal pathway,which may contribute to the improvement of dendritic spine abnormalities in autism spectrum disorders.

关键词： autism Ctnnd2 deletion GABAergic neurons melatonin PI3K/Akt signal pathway prefrontal cortex social behavior spine density synaptic-associated proteins

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

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

Short-term environmental enrichment exposure induces proliferation and maturation of doublecortin-positive cells in the prefrontal cortex

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Neural Regeneration Research 2014年第3期9卷 318-328页

作者： Chunling Fan Mengqi Zhang Lei Shang Ngobe Akume Cynthia Zhi Li Zhenyu Yang Dan Chen Jufang Huang Kun Xiong Department of Anatomy and Neurobiology Central South University School of Basic Medical Sciences Grade 2006 Eight-year Medicine Doctor Program Central South University Xiangya School of Medicine Grade 2011 Six-year Medicine Program of International Student Central South University Xiangya School of Medicine Grade 2008 Eight-year Medicine Doctor Program Central South University Xiangya School of Medicine

Previous studies have demonstrated that doublecortin-positive immature neurons exist pre- dominantly in the superficial layer of the cerebral cortex of adult mammals such as guinea pigs, and these neurons exhibit very weak properties of self-proliferation during adulthood under physiological conditions. To verify whether environmental enrichment has an impact on the proliferation and maturation of these immature neurons in the prefrontal cortex of adult guinea pigs, healthy adult guinea pigs were subjected to short-term environmental enrichment. Animals were allowed to play with various cognitive and physical stimulating objects over a period of 2 weeks, twice per day, for 60 minutes each. Immunofluorescence staining results indicated that the number of doublecortin-positive cells in layer II of the prefrontal cortex was significantly increased after short-term environmental enrichment exposure. In addition, these doublecortin-positive cells co-expressed 5-bromo-2-deoxyuridine （a marker of cell prolifera- tion）, c-Fos （a marker of cell viability） and NeuN （a marker of mature neurons）. Experimental findings showed that short-term environmental enrichment can induce proliferation, activation and maturation of doublecortin-positive cells in layer II of the prefrontal cortex of adult guinea pigs.

关键词： nerve regeneration neurogenesis prefrontal cortex neocortex guinea pig doublecortinprotein cell proliferation neurons 5-bromodeoxyuridine NSFC grant neural regeneration

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 contexts.Rats 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

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 schizophrenia.The prefrontal cortex(PFC)is an important region for antipsychotics’therapeutic effects.The PFC inflammatory and immune pathways are associated with schizophrenia pathogenesis.However,the effect of antipsychotics on the inflammatory and immune pathways in the PFC remains unclear.We aimed to examined the time-dependent effect of olanzapine on inflammatory and immune markers in the PFC of rats.Since 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 stress.Methods 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 blotting.Results 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 CD14.Olanzapine treatment for 1 day,8 and 36 days also induced ER stress in the PFC.Co-treatment with an ER stress inhibitor,4-phenylbutyrate,inhibited olanzapine-induced inflammation and the immune response in the PFC.Conclusion These results suggested olanzapine exposure could be a factor that induces central inflammation and immunological abnormities in schizophrenia subjects.Olanzapine induces PFC inflammation and immune response,possibly via activating ER stress signaling.

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

Altered functional connectivity of prefrontal cortex in chronic heroin abusers

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Neural Regeneration Research 2011年第28期6卷 2193-2197页

作者： Yinbao Qi Xianming Fu Ruobing Qian Chaoshi Niu Xiangpin Wei Department of Neurosurgery Anhui Provincial Hospital Anhui Medical University Hefei 230001 Anhui Province China

In this study, we investigated alterations in the resting-state functional connectivity of the prefrontal cortex in chronic heroin abusers using functional magnetic resonance imaging. We found that, compared with normal controls, in heroin abusers the left prefrontal cortex showed decreased functional connectivity with the left hippocampus, right anterior cingulate, left middle frontal gyrus, right middle frontal gyrus and right precuneus. However, the right prefrontal cortex showed decreased functional connectivity with the left orbital frontal cortex and the left middle frontal gyrus in chronic heroin abusers. These alterations of resting-state functional connectivity in the prefrontal cortices of heroin abusers suggest that their frontal executive neural network may be impaired, and that this may contribute to their continued heroin abuse and relapse after withdrawal.

关键词： heroin abuse resting-state functional magnetic resonance imaging prefrontal cortex functional connectivity cognitive control