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adult neurogenesis:a real hope or a delusion?

Neural Regeneration Research 2024年第1期19卷 6-15页

作者： Ghulam Hussain Rabia Akram Haseeb Anwar Faiqa Sajid Tehreem Iman Hyung Soo Han Chand Raza Jose-Luis Gonzalez De Aguilar Neurochemicalbiology and Genetics Laboratory(NGL) Department of PhysiologyFaculty of Life SciencesGovernment College UniversityFaisalabadPunjabPakistan Department of Physiology School of MedicineClinical Omics InstituteKyungpook National UniversityDaeguKorea Department of Zoology Faculty of Chemistry and Life SciencesGovernment College UniversityLahorePakistan INSERM U1118Mécanismes Centraux et Péripheriques de la NeurodégénérescenceStrasbourgFranceUniversitéde StrasbourgStrasbourgFrance

adult neurogenesis,the process of creating new neurons,involves the coordinated division,migration,and differentiation of neural stem cells.This process is restricted to neurogenic niches located in two distinct areas of the brain:the subgranular zone of the dentate gyrus of the hippocampus and the subventricular zone of the lateral ventricle,where new neurons are generated and then migrate to the olfactory bulb.neurogenesis has been thought to occur only during the embryonic and early postnatal stages and to decline with age due to a continuous depletion of neural stem cells.Interestingly,recent years have seen tremendous progress in our understanding of adult brain neurogenesis,bridging the knowledge gap between embryonic and adult neurogenesis.Here,we discuss the current status of adult brain neurogenesis in light of what we know about neural stem cells.In this notion,we talk about the importance of intra cellular signaling molecules in mobilizing endogenous neural stem cell prolife ration.Based on the current understanding,we can declare that these molecules play a role in targeting neurogenesis in the mature brain.However,to achieve this goal,we need to avoid the undesired proliferation of neural stem cells by controlling the necessary checkpoints,which can lead to tumorigenesis and prove to be a curse instead of a blessing or hope.

关键词： adult neurogenesis aging brain-derived neurotrophic factor dentate gyrus hippocampus neural stem cells neurotrophic factors Notch oxidative stress stem cells subgranular zone

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Proteomic-based evidence for adult neurogenesis in birds and mammals as indicated from cerebrospinal fluid

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Neural Regeneration Research 2022年第12期17卷 2576-2581页

作者： Eleni Voukali Michal Vinkler Department of Zoology Faculty of ScienceCharles UniversityPragueCzech Republic

adult neurogenesis is the life-long process of neural stem cell proliferation,differentiation into neurons,migration,and incorporation into the existing neuronal circuits.After decades of research,it is now widely accepted that mammals and birds retain the capacity to regenerate neurons even after their subadult ontogeny.Cerebrospinal fluid participates in the regulation of the neurogenic niches of the vertebrate brain through signaling pathways not fully elucidated.Proteomic studies of cerebrospinal fluid have the potential to allow the in-depth characterization of its molecular composition.Comparative studies help to delineate those pathways that are universally critical for the regulation of neurogenesis in adulthood.In this review,we performed literature-based data mining in studies using liquid chromatography-tandem mass spectroscopy that analyzed cerebrospinal fluid samples from healthy adult humans(Homo sapiens);mice(Mus musculus);sheep(Ovis aries);chickens(Gallus gallus);and two parrot species,the budgerigar(Melopsittacus undulatus)and cockatiel(Nymphicus hollandicus).We identified up to 911 proteins represented in cerebrospinal fluid,involved in various pathways regulating adult neurogenesis.However,only 196 proteins were common across humans,mice,and birds.Pathway components involved in nervous system development,cell migration,and axonal guidance were commonly evident in all species investigated so far.Extensive bioinformatic analysis revealed that the universally over-represented pathways involved L1 cell adhesion molecule protein interactions,cell-adhesion molecules,signals regulating extracellular matrix remodeling,regulation of insulin growth factor signaling,axonal guidance,programmed cell death,immune signaling,and post-translational modifications.Most of the reported proteins are part of extracellular vesicles enriched in cerebrospinal fluid.However,the information presently available is still highly fragmentary,and far more questions persist than are answered.Technological advances will allow c

关键词： adult neurogenesis birds cerebrospinal fluid chicken comparative proteomics human mammals mass spectrometry parrots

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adult neurogenesis and pattern separation in rodents： A critical evaluation of data, tasks and interpretation

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Frontiers in Biology 2016年第3期11卷 168-181页

作者： Martha Hvoslef-Eide Charlotte A. Oomen Department of Psychology University of Cambridge Cambridge CB2 3EB United Kingdom Behavioural and Clinical Neuroscience Institute University of Cambridge Cambridge CB2 3 EB United Kingdom Current addess Department of Bioscienees University of Oslo 0370 Oslo Norway Department of Cognitive Neuroseienee Radboud University Medical Center Donders Institute Geert Grooteplein 21 6500 HB Nijmegen The Netherlands Current address Centre for Neuroscience Swammerdam Institute for Life Sciences University of Amsterdam Science Park 904 1098 XH Amsterdam The Netherlands Current address Department of Molecular and Cellular Neurobiology Center for Neurogenomics and Cognitive Research Neuroscience Campus Amsterdam VU University Amsterdam Amsterdam De Boelelaan 1085 1081 HV Amsterdam The Netherlands

The ability to discriminate and store similar inputs as distinct representations in memory is thought to rely on a process called pattern separation in the dentate gyrus of the hippocampus. Recent computational and empirical findings support a role for adult-born granule neurons in spatial pattern separation. We reviewed rodent studies that have manipulated both hippocampal adult neurogenesis and assessed pattern separation. The majority of studies report a supporting role of adult born neurons in pattern separation as measured at the behavioral level. However, closer evaluation of the published findings reveals variation in both pattern separation tasks and in the interpretation of behavioral performance that, taken together, suggests that the role of hippocampal adult neurogenesis in pattern separation may be less established than is currently assumed. Assessment of pattern separation at the network level through the use of immediate early gene expression, optogenetic, pharmacogenetic and/or in vivo electrophysiology studies could be instrumental in further confirming a role of adult born neurons in pattern separation further. Finally, hippocampal adult neurogenesis and pattern separation are not an exclusive pair, as evidence for hippocampal adult neurogenesis contributing to the temporal separation of events in memory, forgetting and cognitive flexibility has also been found. We conclude that whereas current empirical evidence for the involvement of hippocampal adult neurogenesis in pattern separation seems supportive, there is a need for careful interpretation of behavioral findings and an integration of the various proposed functions of adult born neurons.

关键词： adult neurogenesis memory pattern separation dentate gyrus behavioral paradigms

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Microglial activation and adult neurogenesis after brain stroke

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Neural Regeneration Research 2021年第3期16卷 456-459页

作者： Ijair R.C.dos Santos Michelle Nerissa C.Dias Walace Gomes-Leal Laboratory of Experimental Neuroprotection and Neuroregeneration Institute of Biological SciencesFederal University of Pará-BrazilBelém-ParáBrazil

The discovery that new neurons are produced in some regions of the adult mammalian brain is a paradigm-shift in neuroscience research.These new-born cells are produced from neuroprogenitors mainly in the subventricular zone at the margin of the lateral ventricle,subgranular zone in the hippocampal dentate gyrus and in the striatum,a component of the basal ganglia,even in humans.In the human hippocampus,neuroblasts are produced even in elderlies.The regulation of adult neurogenesis is a complex phenomenon involving a multitude of molecules,neurotransmitters and soluble factors released by different sources including glial cells.Microglia,the resident macrophages of the central nervous system,are considered to play an important role on the regulation of adult neurogenesis both in physiological and pathological conditions.Following stroke and other acute neural disorders,there is an increase in the numbers of neuroblast production in the neurogenic niches.Microglial activation is believed to display both beneficial and detrimental role on adult neurogenesis after stroke,depending on the activation level and brain location.In this article,we review the scientific evidence addressing the role of microglial activation on adult neurogenesis after ischemia.A comprehensive understanding of the microglial role after stroke and other neural disorders it is an important step for development of future therapies based on manipulation of adult neurogenesis.

关键词： adult neurogenesis hippocampus ischemia microglia neuroinflammation neuroprotection stroke subventricular zone therapy

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adult mammalian neurogenesis and motivated behaviors

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Integrative Zoology 2018年第6期13卷 655-672页

作者： Claudia JORGENSEN Behavioral Science Department Utah Valley UniversityOremUtahUSA

adult neurogenesis continues to captivate the curiosity of the scientific community;and researchers seem to have a particular interest in identifying the functional implications of such plasticity.While the majority of research focuses on the association between adult neurogenesis and learning and memory(including spatial learning associated with hippocampal neurogenesis and olfactory discrimination associated with neurogenesis in the olfactory system),the following review will explore the link to motivated behaviors.In particular,goal-directed behaviors such as sociosexual,parental,aggressive,as well as depression-and anxiety-like behaviors and their reciprocal association to adult neurogenesis will be evaluated.The review will detail research in humans and other mammalian species.Furthermore,the potential mechanisms underlying these neurogenic alterations will be highlighted.Lastly,the review will conclude with a discussion on the functional significance of these newly generated cells in mediating goal-directed behaviors.

关键词： adult neurogenesis aggression anxiety depression reproduction

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adult neurogenesis: Is it showtime for clinical translation?

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Genes & Diseases 2015年第4期2卷 291-292页

作者： Yu-Jie Lai Fei Sun Guo-Jun Chen Department of Neurology The First Affiliated HospitalChongqing Medical Universityand The Chongqing Key Laboratory of NeurologyChongqing 400016China Department of Physiology Wayne State University School of MedicineDetroitMl 48201USA

The existence of adult stem cells was first described in tissues with high proliferation rates,such as the hematopoietic system and the intestine.Since then,stem cells have been found in almost all adult tissues,including the nervous system.adult neurogenesis is supported by multipotent neural stem cells(NSCs),which maintain some of the cellular and molecular characteristics of their embryonic counterparts.Because of their suggestive appeal as therapeutic agents and their presumed relevance for cognition in health and disease,adult neurogenesis is attracting considerable attention from neuroscientists.

关键词： adult neurogenesis Astroglia B1 cells Multipotent neural stem cells(NSCs) Neurological disorders

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Versatile strategies for adult neurogenesis:avenues to repair the injured brain

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Neural Regeneration Research 2024年第4期19卷 774-780页

作者： Junyi Zhao Siyu Liu Xianyuan Xiang Xinzhou Zhu The Brain Cognition and Brain Disease Institute(BCBDI) Shenzhen Institute of Advanced TechnologyChinese Academy of Sciences Faculty of Life and Health Sciences Shenzhen Institutes of Advanced TechnologyChinese Academy of Sciences Shenzhen-Hong Kong Institute of Brain Science-Shenzhen Fundamental Research Institutions

Brain injuries due to trauma or stroke are major causes of adult death and disability.Unfortunately,few interventions are effective for post-injury repair of brain tissue.After a long debate on whether endogenous neurogenesis actually happens in the adult human brain,there is now substantial evidence to support its occurrence.Although neurogenesis is usually significantly stimulated by injury,the reparative potential of endogenous differentiation from neural stem/progenitor cells is usually insufficient.Alternatively,exogenous stem cell transplantation has shown promising results in animal models,but limitations such as poor long-term survival and inefficient neuronal differentiation make it still challenging for clinical use.Recently,a high focus was placed on glia-to-neuron conversion under single-factor regulation.Despite some inspiring results,the validity of this strategy is still controversial.In this review,we summarize historical findings and recent advances on neurogenesis strategies for neurorepair after brain injury.We also discuss their advantages and drawbacks,as to provide a comprehensive account of their potentials for further studies.

关键词： adult neurogenesis glia-to-neuron conversion ischemic stroke neurogenic niche neuroinflammation stem cell transplantation traumatic brain injury

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The role of exosomes in adult neurogenesis:implications for neurodegenerative diseases

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Neural Regeneration Research 2024年第2期19卷 282-288页

作者： Zhuoyang Yu Yan Teng Jing Yang Lu Yang Institute of Neurology Sichuan Provincial People’s HospitalUniversity of Electronic Science and Technology of ChinaChengduSichuan ProvinceChina Laboratory of Aging Research School of MedicineUniversity of Electronic Science and Technology of ChinaChengduSichuan ProvinceChina

Exosomes are cup-shaped extracellular vesicles with a lipid bilayer that is approximately 30 to 200 nm in thickness.Exosomes are widely distributed in a range of body fluids,including urine,blood,milk,and saliva.Exosomes exert biological function by transporting factors between different cells and by regulating biological pathways in recipient cells.As an important form of intercellular communication,exosomes are increasingly being investigated due to their ability to transfer bioactive molecules such as lipids,proteins,mRNAs,and microRNAs between cells,and because they can regulate physiological and pathological processes in the central nervous system.adult neurogenesis is a multistage process by which new neurons are generated and migrate to be integrated into existing neuronal circuits.In the adult brain,neurogenesis is mainly localized in two specialized niches:the subventricular zone adjacent to the lateral ventricles and the subgranular zone of the dentate gyrus.An increasing body of evidence indicates that adult neurogenesis is tightly controlled by environmental conditions with the niches.In recent studies,exosomes released from different sources of cells were shown to play an active role in regulating neurogenesis both in vitro and in vivo,thereby participating in the progression of neurodegenerative disorders in patients and in various disease models.Here,we provide a state-of-the-art synopsis of existing research that aimed to identify the diverse components of exosome cargoes and elucidate the therapeutic potential of exosomal contents in the regulation of neurogenesis in several neurodegenerative diseases.We emphasize that exosomal cargoes could serve as a potential biomarker to monitor functional neurogenesis in adults.In addition,exosomes can also be considered as a novel therapeutic approach to treat various neurodegenerative disorders by improving endogenous neurogenesis to mitigate neuronal loss in the central nervous system.

关键词： adult neurogenesis Alzheimer’s disease amyotrophic lateral sclerosis exosome Huntington’s disease neurodegenerative disease neurogenic niches Parkinson’s disease

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Transgenic mouse models for studying adult neurogenesis

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Frontiers in Biology 2016年第3期11卷 151-167页

作者： Fatih Semerci Mirjana Maletic-Savatic Program in Developmental Biology Baylor College of Medicine Houston TX 77030 USA Jan and Dan Duncan Neurological Research Institute at Texas Children's Hospital Houston TX 77030 USA Department of Pediatrics-Neurology Department of Neuroscience and Structural and Computational Biology and Molecular Biophysics Baylor College of Medicine Houston TX 77030 USA

The mammalian hippocampus shows a remarkable capacity for continued neurogenesis throughout life. Newborn neurons, generated by the radial neural stem cells （NSCs）, are important for learning and memory as well as mood control. During aging, the number and responses of NSCs to neurogenic stimuli diminish, leading to decreased neurogenesis and age-associatedcognitive decline and psychiatric disorders. Thus, adult hippocampal neurogenesis has garnered significant interest because targeting it could be a novel potential therapeutic strategy for these disorders. However, if we are to use nenrogenesis to halt or reverse hippocampal-related pathology, we need to understand better the core molecular machinery that governs NSC and their progeny. In this review, we summarize a wide variety of mouse models used in adult neurogenesis field, present their advantages and disadvantages based on specificity and efficiency of labeling of different cell types, and review their contribution to our understanding of the biology and the heterogeneity of different cell types found in adult neurogenic niches.

关键词： adult neurogenesis mouse models neural stem cells neuroprogenitors lineage tracing

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Features of adult neurogenesis and neurochemical signaling in the Cherry salmon Oncorhynchus masou brain

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Neural Regeneration Research 2013年第1期8卷 13-23页

作者： Evgeniya V. Pushchina Dmitry K. Obukhov Anatoly A. Varaksin Laboratory of Cytophysiology Institute of Marine Biology Far East Branch Russian Academy of Sciences St. Petersburg State University

We investigated the distribution of gamma aminobutyric acid, tyrosine hydroxylase and nitric oxide-producing elements in a cherry salmon Oncorhynchus masou brain at various stages of postnatal ontogenesis by immunohistochemical staining and histochemical staining. The periventricular region cells exhibited the morphology of neurons and glia including radial glia-like cells and contained several neurochemical substances. Heterogeneous populations of tyrosine hydroxylase-, gamma aminobutyric acid-immunoreactive, as well as nicotinamide adenine dinucleotide phosphate diaphorase-positive cells were observed in proliferating cell nuclear antigen-immunoreactive proliferative zones in periventricular area of diencephalon, central grey layer of dorsomedial tegmentum, medulla and spinal cord. Immunolocalization of Pax6 in the cherry salmon brain revealed a neuromeric construction of the brain at various stages of postnatal ontogenesis, and this was confirmed by tyrosine hydroxylase and gamma aminobutyric acid labeling.

关键词： neural regeneration neurogenesis teleostei adult neurogenesis neurotransmitter signaling migration tyrosine hydroxylase gamma aminobutyric acid development Pax6 NADPH-diaphorase proliferation grant-supported paper neuroregeneration

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