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Effects of reproductive experience on paternal behavior,levels of testosterone,prolactin in serum and dendritic spines in medial prefrontal cortex of mandarin voles

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Integrative Zoology 2018年第6期13卷 711-722页

作者： Bo WANG Laifu LI Zhixiong HE Limin WANG Siyi ZHANG Hui QIAO Rui JIA Fadao TAI Institute of Brain and Behavioral Sciences College of Life SciencesShaanxi Normal UniversityXi’anShaanxiChina Genetic Engineering Laboratory College of Biological and Environmental engineeringXi’an UniversityXi’anShaanxiChina

Maternal behaviors and brains change dramatically with pregnancy,parturition and other mothering experiences.However,whether paternal behavior,brain plasticity and levels of relevant hormones also change along with fathering experience and pups’age remains unclear.Using socially monogamous mandarin voles(Micro-tus mandarinus),we found that experienced fathers exhibited more active paternal behaviors,such as licking,retrievals and nest building,but less paternal care,such as huddling,than new fathers.The high levels of licking and nest building appeared in the earlier days of their mate’s lactation.Experienced fathers retrieved 9–13-day-old pups more frequently.However,these paternal behaviors did not show significant changes with age of pups in new fathers.In addition,experienced fathers had dramatically higher prolactin levels than new fathers but had similar concentrations of testosterone to new fathers.New fathers had lower levels of testosterone but higher levels of prolactin than new paired males.The fathers had higher prolactin levels in the earlier days of their mate’s lactation.The new and experienced fathers had similar dendritic length and spine density on pyramidal neurons in the medial prefrontal cortex but displayed higher levels than new paired males.Taken together,these results indicate that reduction of testosterone levels and increase of prolactin levels may be associated with initiation of paternal care.Fathering experience significantly affects levels of parental care and paternal behaviors toward different aged pups,and brain plasticity can also be enhanced by transition to fatherhood.

关键词： dendritic spines paternal behavior prolactin reproductive experience testosterone

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Effects of ketamine and midazolam on morphology of dendritic spines in hippocampal CA1 region of neonatal mice

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Chinese Medical Journal 2009年第4期122卷 455-459页

作者： TAN Hong REN Rong-rong XIONG Zhi-qi WANG Ying-wei Department of Anesthesiology Xinhua Hospital Shanghai JiaoTong University College of Medicine Shanghai 200092 China Institute of Neuroscience and Key Laboratory of Neurobiology Shanghai Institutes for Biological Sciences Chinese Academy ofSciences Shanghai 200031 China

Background It is a common phenomenon that children experience multiple general anesthesias in clinical practice, which raises the question whether repeated exposure to general anesthetics would interfere with the development of the central nervous system of children. The present study was designed to evaluate the effects of repeated treatment with ketamine or midazolam on postnatal dendrite development by examining the morphology of the dendritic spines of the pyramidal neurons in the hippocampal CA1 region in mice. Methods The transgenic green fluorescent protein-M line （GFP-M） mice were used in this study. Ketamine （100 mg/kg） midazolam （50 mg/kg） or saline （10 ml/kg） was administered intraperitoneally once a day on consecutive days from postnatal day 8 （P8） to postnatal day 12 （P12）. At postnatal day 13 （P13） and postnatal day 30 （P30）, the density and length of the apical dendritic spines of the pyramidal neurons in the hippocampal CA1 region were examined under a confocal microscope. Results At P13, for both the ketamine group and the midazolam group, the dendritic spines were found with a comparatively lower density and longer average length than in the control group. At P30, no significant difference in the density or average length of dendritic spines was found between the anesthetic group and control group. Conclusions This study indicated that repeated exposure to ketamine or midazolam in neonatal mice impaired dendritic spine maturation immediately afterwards, but this influence seemed to disappear during further postnatal development.

关键词： dendritic spines ketamine midazolam confocal

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c-Abl kinase at the crossroads of healthy synaptic remodeling and synaptic dysfunction in neurodegenerative diseases

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Neural Regeneration Research 2023年第2期18卷 237-243页

作者： Daniela A.Gutiérrez América Chandía-Cristi María JoséYáñez Silvana Zanlungo Alejandra R.Alvarez Cell Signaling Laboratory Department of Cellular and Molecular BiologyCenter for Aging and Regeneration(CARE)Millennium Institute on Immunology and ImmunotherapyBiological Sciences FacultyPontificia Universidad Católica de ChileSantiagoChile School of Medical Technology Health Sciences FacultyUniversidad San SebastianSede Los LeonesSantiagoChile Department of Gastroenterology Faculty of MedicinePontificia Universidad Católica de ChileSantiagoChile

Our ability to learn and remember depends on the active formation,remodeling,and elimination of synapses.Thus,the development and growth of synapses as well as their weakening and elimination are essential for neuronal rewiring.The structural reorganization of synaptic complexes,changes in actin cytos keleton and organelle dynamics,as well as modulation of gene expression,determine synaptic plasticity.It has been proposed that dys regulation of these key synaptic homeostatic processes underlies the synaptic dysfunction observed in many neurodegenerative diseases.Much is known about downstream signaling of activated N-methyl-D-aspartate andα-amino-3-hydroxy-5-methyl-4-isoazolepro pionate receptors;howeve r,other signaling pathways can also contribute to synaptic plasticity and long-lasting changes in learning and memory.The non-receptor tyrosine kinase c-Abl(ABL1)is a key signal transducer of intra and extracellular signals,and it shuttles between the cyto plasm and the nucleus.This review focuses on c-Abl and its synaptic and neuronal functions.Here,we discuss the evidence showing that the activation of c-Abl can be detrimental to neurons,promoting the development of neurodegenerative diseases.Nevertheless,c-Abl activity seems to be in a pivotal balance between healthy synaptic plasticity,regulating dendritic spines remodeling and gene expression after cognitive training,and synaptic dysfunction and loss in neurodegenerative diseases.Thus,c-Abl genetic ablation not only improves learning and memory and modulates the brain genetic program of trained mice,but its absence provides dendritic spines resiliency against damage.Therefo re,the present review has been designed to elu cidate the common links between c-Abl regulation of structural changes that involve the actin cytos keleton and organelles dynamics,and the transc riptional program activated during synaptic plasticity.By summarizing the recent discove ries on c-Abl functions,we aim to provide an overview of how its inhibition co uld be a potentially fruitful

关键词： actin cytoskeleton activity-dependent plasticity Alzheimer's disease c-Abl dendritic spines learning synapse synaptic plasticity transcription tyrosine kinase

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Neurotrophic fragments as therapeutic alternatives to ameliorate brain aging

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Neural Regeneration Research 2023年第1期18卷 51-56页

作者： Itzel Ortiz Flores Samuel Treviño Alfonso Díaz Department of Health Sciences School of MedicineUniversity of the Americas PueblaPueblaMexico Faculty of Chemical Sciences Benemerita Autonomous University of PueblaPueblaMexico

Aging is a global phenomenon and a complex biological process of all living beings that introduces various changes.During this physiological process,the brain is the most affected organ due to changes in its structural and chemical functions,such as changes in plasticity and decrease in the number,diameter,length,and branching of dendrites and dendritic spines.Likewise,it presents a great reduction in volume resulting from the contraction of the gray matter.Consequently,aging can affect not only cognitive functions,including learning and memory,but also the quality of life of older people.As a result of the phenomena,various molecules with notable neuroprotective capacity have been proposed,which provide a therapeutic alternative for people under conditions of aging or some neurodegenerative diseases.It is important to indicate that in recent years the use of molecules with neurotrophic activity has shown interesting results when evaluated in in vivo models.This review aims to describe the neurotrophic potential of molecules such as resveratrol(3,5,4′-trihydroxystilbene),neurotrophins(brain-derived neurotrophic factor),and neurotrophic-type compounds such as the terminal carboxyl domain of the heavy chain of tetanus toxin,cerebrolysin,neuropeptide-12,and rapamycin.Most of these molecules have been evaluated by our research group.Studies suggest that these molecules exert an important therapeutic potential,restoring brain function in aging conditions or models of neurodegenerative diseases.Hence,our interest is in describing the current scientific evidence that supports the therapeutic potential of these molecules with active neurotrophic.

关键词： Alzheimer’s disease brain cerebral cortex cognitive function dendritic spines HC-TeTx hippocampus neurodegeneration neuronal survival neurotrophins

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dendritic spine density changes and homeostatic synaptic scaling:a meta-analysis of animal studies

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Neural Regeneration Research 2022年第1期17卷 20-24页

作者： Thiago C.Moulin Danielle Rayêe Helgi B.Schiöth Functional Pharmacology Unit Department of NeuroscienceUppsala UniversityUppsalaSweden Institute of Medical Biochemistry Federal University of Rio de JaneiroRio de JaneiroBrazil Institute of Biomedical Sciences Federal University of Rio de JaneiroRio de JaneiroBrazil Department of Ophthalmology and Visual Sciences Albert Einstein College of MedicineNYUSA Institute for Translational Medicine and Biotechnology Sechenov First Moscow State Medical UniversityMoscowRussia

Mechanisms of homeostatic plasticity promote compensatory changes of cellular excitability in response to chronic changes in the network activity.This type of plasticity is essential for the maintenance of brain circuits and is involved in the regulation of neural regeneration and the progress of neurodegenerative disorders.One of the most studied homeostatic processes is synaptic scaling,where global synaptic adjustments take place to restore the neuronal firing rate to a physiological range by the modulation of synaptic receptors,neurotransmitters,and morphology.However,despite the comprehensive literature on the electrophysiological properties of homeostatic scaling,less is known about the structural adjustments that occur in the synapses and dendritic tree.In this study,we performed a meta-analysis of articles investigating the effects of chronic network excitation(synaptic downscaling)or inhibition(synaptic upscaling)on the dendritic spine density of neurons.Our results indicate that spine density is consistently reduced after protocols that induce synaptic scaling,independent of the intervention type.Then,we discuss the implication of our findings to the current knowledge on the morphological changes induced by homeostatic plasticity.

关键词： chronic inhibition chronic stimulation dendritic spines downscaling excitability homeostatic plasticity spine density synaptic scaling upscaling

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Cdk5-mediated phosphorylation is required for the development and plasticity of dendritic spines

Cdk5-mediated phosphorylation is required for the developmen...

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中国生理学会第24届全国会员代表大会暨生理学学术大会

作者： Lai Kwok On The University of Hong Kong Department of Physiology

Neurons change their synaptic connectivity by experience,which is fundamental to brain maturation and functions such as learning and memory.To elucidate the molecular mechanisms,one common approach is to study the changes of synapses in primary neurons upon manipulation of synaptic activity.Mostexcitatory synapses are located on specialized dendritic compartments called dendritic spines,which possess heterogeneous morphologies and are highly dynamic.Spine stability and morphology are influenced by synaptic activity and specific growth factors such as the neurotrophin BDNF,and involve signaling cascades regulated through multiple series of protein phosphorylation.Here I will describe the importance of the protein kinase Cdk5 in dendritic spine morphogenesis and synaptic function via phosphorylation of the BDNF receptor Trk B and the signaling protein S6 kinase.

关键词： dendritic spines kinase phosphorylation neurotrophin

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Microglia and astrocytes mediate synapse engulfment in a MER tyrosine kinase-dependent manner after traumatic brain injury

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Neural Regeneration Research 2023年第8期18卷 1770-1776页

作者： Hui Shen Xiao-Jing Shi Lin Qi Cheng Wang Muyassar Mamtilahun Zhi-Jun Zhang Won-Suk Chung Guo-Yuan Yang Yao-Hui Tang Med-X Research Institute and School of Biomedical Engineering Shanghai Jiao Tong UniversityShanghaiChina Department of Biological Sciences Korea Advanced Institute of Science and TechnologyDaejeonSouth Korea

Recent studies have shown that microglia/macrophages and astrocytes can mediate synaptic phagocytosis through the MER proto-oncokinase in developmental or stroke models,but it is unclear whether the same mechanism is also active in traumatic brain injury.In this study,we established a mouse model of traumatic brain injury and found that both microglia/macrophages and astrocytes phagocytosed synapses and expression of the MER proto-oncokinase increased 14 days after injury.Specific knockout of MER in microglia/macrophages or astrocytes markedly reduced injury volume and greatly improved neurobehavioral function.In addition,in both microglia/macrophages-specific and astrocytes-specific MER knock-out mice,the number of microglia/macrophage and astrocyte phagocytosing synapses was markedly decreased,and the total number of dendritic spines was increased.Our study suggested that MER proto-oncokinase expression in microglia/macrophages and astrocytes may play an important role in synaptic phagocytosis,and inhibiting this process could be a new strategy for treating traumatic brain injury.

关键词： animal model astrocyte dendritic spines lysosome macrophage MER proto-oncokinase microglia neurologic function phagocytosis synapse engulfment traumatic brain injury

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Effects of Danggui-Shaoyao-San on the Influence of Spatial Learning and Memory Induced by Experimental Tooth Movement

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Chinese Medical Journal 2015年第14期128卷 1948-1955页

作者： Hong-Shi Li Jie Ke Gui-Zhi Zhao Li-An Wu Jun-Ping Kou Hong-Chen Liu Department of Stomatology of the General Air Force Hospital Beijing 100142 China Department of Paediatric Dentistry School of Stomatology Fourth Military Medical University Xi'an Shaanxi 710032 China State Key Laboratory of Natural Medicines China Pharmaceutical University Nanjing Jiangsu 210038 China Institute of Stomatology Chinese PLA General Hospital Beijing 100853 China

Background： The pain caused by orthodontic treatment has been considered as tough problems in orthodontic practice. There is substantial literature on pain which has exactly effected on learning and memory; orthodontic tooth movement affected the emotional status has been showed positive outcomes. Danggui-Shaoyao-San （DSS） is a Traditional Chinese Medicine prescription that has been used for pain treatment and analgesic effect for orthodontic pain via inhibiting the activations of neuron and glia. We raised the hypothesis that DSS could restore the impaired abilities of spatial learning and memory via regulating neuron or glia expression in the hippocampus. Methods： A total of 36 rats were randornly divided into three groups：（ 1 ） Sham group （n = 12）, rats underwent all the operation procedure except for the placement of orthodontic forces and received saline treatment：（2） experimental tooth movement （ETM） group （n - 12）, rats received saline treatment and ETM：（3） DSS ＋ ETM （DETM） group （n = 12）, rats received DSS treatment and ETM. All DETM group animals were administered with DSS at a dose of 150 mg/kg. Monis water maze test was evaluated： immunofluorescent histochemistry was used to identity astrocytes activation, and immunofluorescent dendritic spine analysis was used to identify the dendritic spines morphological characteristics expression levels in hippocampus. Results： Maze training sessions during the 5 successive days revealed that ETM significantly deficits in progressive learning in rats, DSS that was given from day 5 prior to ETM enhanced progressive learning. The ETM group rats took longer to cross target quadrant during the probe trial and got less times to cross-platform than DETM group. The spine density in hippocampus in ETM group was significantly decreased cornpared to the sham group. In addition, thin and mature spine density were decreased too. However, the DSS administration could reverse the dendritic shrinkage and increase the spine density compared to the ETM group. Astrocytes acti

关键词： Astrocytes Danggui-Shaoyao-San dendritic spines Experimental Tooth Movement Hippocampus Spatial Learning and Memory

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Synaptic metaplasticity through NMDA receptor lateral diffusion

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南京医科大学学报(自然科学版) 2008年第5期 645-645页

作者： Zhao, J. Peng, Y. Xu, Z. Chen, R. Q. Gu, Q. H. Chen, Z. Lu, W. Nanjing Med Univ, Dept Neurobiol, Key Lab Neurodegenerat Dis Jiangsu Prov, Nanjing 210029, Jiangsu Prov, Peoples R China. Nanjing Med Univ, Key Lab Human Funct Gen Jiangsu Prov, Nanjing 210029, Jiangsu Prov, Peoples R China

Lateral diffusion of glutamate receptors was proposed as a mechanism for regulating receptor numbers at synapses and affecting synaptic functions, especially the efficiency of synaptic transmission. However, a direct link between receptor lateral diffusion and change in synaptic function has not yet been established. In the present study, we demonstratedNMDAreceptor(NMDAR) lateral diffusion in CA1 neurons in hippocampal slices by detecting considerable recovery of spontaneous or evoked EPSCs from the block of (+)-MK-801[(+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d] cyclohepten-5,10-imine maleate], an irreversible NMDAR open-channel blocker. We observed changes on both the number and the composition of synaptic NMDAR on recovery. More importantly, after the recovery, long-term potentiation(LTP)-producing protocol induced only LTD(long-term depression) instead of LTP. In contrast, a complete recovery from competitive NMDAR blocker D,L-AP-5 was observed without subsequent changes on synaptic plasticity. Our data suggest a revised model of NMDAR trafficking wherein extrasynaptic NMDARs, mostly NR1/NR2B receptors, move laterally into synaptic sites, resulting in altered rule of synaptic modification. Thus, CA1 synapses exhibit a novel form of metaplasticity in which the direction of synaptic modification can be reverted through subtype-specific lateral diffusion of NMDA receptors.

关键词： NMDA receptor lateral diffusion LTP LTD MK-801 AP-5 long-term potentiation activity-dependent regulation cultured hippocampal-neurons mouse visual-cortex ampa receptor differential roles dendritic spines plasticity activation trafficking

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The Protocadherin 17 Gene Affects Cognition, Personality, Amygdala Structure and Function, Synapse Development and Risk of Major Mood Disorders

The Protocadherin 17 Gene Affects Cognition, Personality, Am...

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中国神经科学学会第十二届全国学术会议

作者： Hong Chang Naosuke Hoshina Yina Ma Hengyi Cao Andreas Meyer-Lindenberg Heike Tost Xiao Xiao Tadashi Yamamoto Ming Li Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences and Yunnan Province Kunming Institute of Zoology Cell Signal Unit Okinawa Institute of Science and Technology Graduate University State Key Laboratory of Cognitive Neuroscience and Learning IDG/McGovern Institute for Brain Research Beijing Normal University Department of Psychiatry and Psychotherapy Central Institute of Mental Health Medical Faculty Mannheim University of Heidelberg

Objective: Major mood disorders, which primarily include bipolar disorder and major depressive disorder, are the leading cause of disability worldwide and pose a major challenge in identifying robust risk genes. Methods: An integrative analysis involving genetics, m RNA expression, cognitive performance, neuroimaging and neurobiology was performed. Results: We present data from independent large-scale clinical datasets（including 29,557 cases and 32,056 controls） revealing brain expressed protocadherin 17（PCDH17） as a susceptibility gene for major mood disorders. Single nucleotide polymorphisms（SNPs） spanning the PCDH17 region are significantly associated with major mood disorders;subjects carrying the risk allele showed impaired cognitive abilities, increased vulnerable personality features, decreased amygdala volume and altered amygdala function as compared with non-carriers. The risk allele predicted higher transcriptional levels of PCDH17 m RNA in postmortem brain samples, which is consistent with increased gene expression in patients with bipolar disorder compared with healthy subjects. Further, overexpression of PCDH17 in primary cortical neurons revealed significantly decreased spine density and abnormal dendritic morphology compared with control groups, which again is consistent with the clinical observations of reduced numbers of dendritic spines in the brains of patients with major mood disorders. Conclusions: Given that synaptic spines are dynamic structures which regulate neuronal plasticity and play crucial roles in myriad brain functions, this study reveals a potential underlying biological mechanism of a novel risk gene for major mood disorders involved in synaptic function and related intermediate phenotypes.

关键词： PCDH17 mood disorders amygdala expression dendritic spines

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