Developmental Neurobiology最新文献

{"title":"Effects of deubiquitylases on the biological behaviors of neural stem cells","authors":"Qiqi Zhao,&nbsp;Yixin Li,&nbsp;Xixun Du,&nbsp;Xi Chen,&nbsp;Qian Jiao,&nbsp;Hong Jiang","doi":"10.1002/dneu.22844","DOIUrl":"10.1002/dneu.22844","url":null,"abstract":"<p>New neurons are generated throughout life in distinct regions of the mammalian brain due to the proliferation and differentiation of neural stem cells (NSCs). Ubiquitin, a post-translational modification of cellular proteins, is an important factor in regulating neurogenesis. Deubiquitination is a biochemical process that mediates the removal of ubiquitin moieties from ubiquitin-conjugated substrates. Recent studies have provided growing evidence that deubiquitylases (DUBs) which reverse ubiquitylation process play critical roles in NSCs maintenance, differentiation and maturation. This review mainly focused on the relationship of DUBs and NSCs, and further summarized recent advances in our understanding of DUBs on regulating NSCs biological behaviors.</p>","PeriodicalId":11300,"journal":{"name":"Developmental Neurobiology","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2021-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/dneu.22844","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39168238","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dynamics of microglia and dendritic spines in early adolescent cortex after developmental alcohol exposure","authors":"Elissa L. Wong,&nbsp;Alexandra Strohm,&nbsp;Jason Atlas,&nbsp;Cassandra Lamantia,&nbsp;Ania K. Majewska","doi":"10.1002/dneu.22843","DOIUrl":"10.1002/dneu.22843","url":null,"abstract":"<p>Fetal alcohol spectrum disorder patients suffer from many cognitive disabilities. These include impaired auditory, visual, and tactile sensory information processing, making it more difficult for these patients to learn to navigate social scenarios. Rodent studies have shown that alcohol exposure during the brain growth spurt (BGS) can lead to acute neuronal apoptosis and an immunological response by microglia in the somatosensory cortex. Since microglia have critical physiological functions, including the support of excitatory synapse remodeling via interactions with dendritic spines, we sought to understand whether BGS alcohol exposure has long-term effects on microglial or dendritic spine dynamics. Using in vivo two-photon microscopy in 4–5 week old mice, we evaluated microglial functions such as process motility, the response to tissue injury, and the dynamics of physical interactions between microglial processes and dendritic spines. We also investigated potential differences in the morphology, density, or dynamics of dendritic spines in layer I/II primary sensory cortex of control and BGS alcohol exposed mice. We found that microglial process motility and contact with dendritic spines were not altered after BGS alcohol exposure. While the response of microglial processes toward tissue injury was not significantly altered by prior alcohol exposure, there was a trend suggesting that alcohol early in life may prime microglia to respond more quickly to secondary injury. Spine density, morphology, stability, and remodeling over time were not perturbed after BGS alcohol exposure. We demonstrate that after BGS alcohol exposure, the physiological functions of microglia and excitatory neurons remain intact in early adolescence.</p>","PeriodicalId":11300,"journal":{"name":"Developmental Neurobiology","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2021-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/dneu.22843","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39155246","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Leucine-rich repeats and immunoglobulin-like domains 1 deficiency affects hippocampal dendrite complexity and impairs cognitive function","authors":"Francisco Javier Hita,&nbsp;Pedro Bekinschtein,&nbsp;Fernanda Ledda,&nbsp;Gustavo Paratcha","doi":"10.1002/dneu.22840","DOIUrl":"10.1002/dneu.22840","url":null,"abstract":"<p>Leucine-rich repeat (LRR) transmembrane proteins have been directly linked to neurodevelopmental and cognitive disorders. We have previously shown that the LRR transmembrane protein, leucine-rich repeats and immunoglobulin-like domains 1 (Lrig1), is a physiological regulator of dendrite complexity of hippocampal pyramidal neurons and social behavior. In this study, we performed a battery of behavioral tests to evaluate spatial memory and cognitive capabilities in <i>Lrig1</i> mutant mice. The cognitive assessment demonstrated deficits in recognition and spatial memory, evaluated by novel object recognition and object location tests. Moreover, we found that <i>Lrig1</i>-deficient mice present specific impairments in the processing of similar but not dissimilar locations in a spatial pattern separation task, which was correlated with an enhanced dendritic growth and branching of Doublecortin-positive immature granule cells of the dentate gyrus. Altogether, these findings indicate that Lrig1 plays an essential role in controlling morphological and functional plasticity in the hippocampus.</p>","PeriodicalId":11300,"journal":{"name":"Developmental Neurobiology","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2021-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/dneu.22840","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39083341","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Aging affects cognition and hippocampal ultrastructure in male Wistar rats","authors":"Nino Lomidze,&nbsp;Mzia G. Zhvania,&nbsp;Yousef Tizabi,&nbsp;Nadezhda Japaridze,&nbsp;Nino Pochkhidze,&nbsp;Fuad Rzayev,&nbsp;Tamar Lordkipanidze","doi":"10.1002/dneu.22839","DOIUrl":"10.1002/dneu.22839","url":null,"abstract":"<p>It is now well established that aging is associated with emotional and cognitive changes. Although the basis of such changes is not fully understood, ultrastructural alterations in key brain areas are likely contributing factors. Recently, we reported that aging-related anxiety in male Wistar rats is associated with ultrastructural changes in the central nucleus of amygdala, an area that plays important role in emotional regulation. In this study, we evaluated the cognitive performance of adolescent, adult, and aged male Wistar rats in multi-branch maze (MBM) as well as in Morris water maze (MWM). We also performed ultrastructural analysis of the CA1 region of the hippocampus, an area intimately involved in cognitive function. The behavioral data indicate significant impairments in few indices of cognitive functions in both tests in aged rats compared to the other two age groups. Concomitantly, a total number of presynaptic vesicles as well as vesicles in the resting pool were significantly lower, whereas postsynaptic mitochondrial area was significantly higher in aged rats compared to the other age groups. No significant differences in presynaptic terminal area or postsynaptic mitochondrial number were detected between the three age groups. These results indicate that selective ultrastructural changes in specific hippocampal region may accompany cognitive decline in aging rats.</p>","PeriodicalId":11300,"journal":{"name":"Developmental Neurobiology","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2021-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/dneu.22839","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39041883","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CG11426 gene product negatively regulates glial population size in the Drosophila eye imaginal disc","authors":"Jong-Eun Rhee,&nbsp;Jin-Hyeon Choi,&nbsp;Jae H. Park,&nbsp;Gyunghee Lee,&nbsp;Banya Pak,&nbsp;Seung-Hae Kwon,&nbsp;Sang-Hak Jeon","doi":"10.1002/dneu.22838","DOIUrl":"10.1002/dneu.22838","url":null,"abstract":"<p>Glial cells play essential roles in the nervous system. Although glial populations are tightly regulated, the mechanisms regulating the population size remain poorly understood. Since <i>Drosophila</i> glial cells are similar to the human counterparts in their functions and shapes, rendering them an excellent model system to understand the human glia biology. Lipid phosphate phosphatases (LPPs) are important for regulating bioactive lipids. In <i>Drosophila</i>, there are three known LPP-encoding genes: <i>wunen</i>, <i>wunen-2</i>, and <i>lazaro</i>. The wunens are important for germ cell migration and survival and septate junction formation during tracheal development. <i>Lazaro</i> is involved in phototransduction. In the present study, we characterized a novel <i>Drosophila</i> LPP-encoding gene, <i>CG11426</i>. Suppression of <i>CG11426</i> increased glial cell number in the eye imaginal disc during larval development, while ectopic <i>CG11426</i> expression decreased it. Both types of mutation also caused defects in axon projection to the optic lobe in larval eye–brain complexes. Moreover, <i>CG11426</i> promoted apoptosis via inhibiting ERK signaling in the eye imaginal disc. Taken together, these findings demonstrated that <i>CG11426</i> gene product negatively regulates ERK signaling to promote apoptosis for proper maintenance of the glial population in the developing eye disc.</p>","PeriodicalId":11300,"journal":{"name":"Developmental Neurobiology","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2021-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/dneu.22838","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39026029","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ultrastructural analysis of dendritic spine necks reveals a continuum of spine morphologies","authors":"Netanel Ofer,&nbsp;Daniel R. Berger,&nbsp;Narayanan Kasthuri,&nbsp;Jeff W. Lichtman,&nbsp;Rafael Yuste","doi":"10.1002/dneu.22829","DOIUrl":"10.1002/dneu.22829","url":null,"abstract":"<p>Dendritic spines are membranous protrusions that receive essentially all excitatory inputs in most mammalian neurons. Spines, with a bulbous head connected to the dendrite by a thin neck, have a variety of morphologies that likely impact their functional properties. Nevertheless, the question of whether spines belong to distinct morphological subtypes is still open. Addressing this quantitatively requires clear identification and measurements of spine necks. Recent advances in electron microscopy enable large-scale systematic reconstructions of spines with nanometer precision in 3D. Analyzing ultrastructural reconstructions from mouse neocortical neurons with computer vision algorithms, we demonstrate that the vast majority of spine structures can be rigorously separated into heads and necks, enabling morphological measurements of spine necks. We then used a database of spine morphological parameters to explore the potential existence of different spine classes. Without exception, our analysis revealed unimodal distributions of individual morphological parameters of spine heads and necks, without evidence for subtypes of spines. The postsynaptic density size was strongly correlated with the spine head volume. The spine neck diameter, but not the neck length, was also correlated with the head volume. Spines with larger head volumes often had a spine apparatus and pairs of spines in a post-synaptic cell contacted by the same axon had similar head volumes. Our data reveal a lack of morphological subtypes of spines and indicate that the spine neck length and head volume must be independently regulated. These results have repercussions for our understanding of the function of dendritic spines in neuronal circuits.</p>","PeriodicalId":11300,"journal":{"name":"Developmental Neurobiology","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2021-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/dneu.22829","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38891260","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"GSK-3β S9A overexpression leads murine hippocampal neural precursors to acquire an astroglial phenotype in vivo","authors":"Miguel Flor-García,&nbsp;Jesús Ávila,&nbsp;María Llorens-Martín","doi":"10.1002/dneu.22823","DOIUrl":"10.1002/dneu.22823","url":null,"abstract":"<p>The addition of new neurons to the existing hippocampal circuitry persists in the adult dentate gyrus (DG). During this process, named adult hippocampal neurogenesis (AHN), adult hippocampal progenitor cells (AHPs) give rise to newborn dentate granule cells (DGCs). The acquisition of a neuronal lineage by AHPs is tightly regulated by numerous signaling molecules and transcription factors. In this regard, glycogen synthase kinase 3β (GSK-3β) is a master regulator of the maturation of AHPs in vitro. Here we analyzed the cell-autonomous effects of overexpressing a constitutively active form of GSK-3β (GSK-3β S9A) in AHPs in vivo. To this end, we stereotaxically injected a GSK-3β S9A-encoding retrovirus (GSK-3β-V5) into the DG of young adult C57BL6/J Ola Hsd female mice and studied the cell lineage acquisition, migratory and marker expression patterns, and the morphological maturation of the infected cells over time. Strikingly, GSK-3β S9A-transduced cells expressed glial fibrillary acidic protein (GFAP) and NG2, thereby acquiring an immature astroglial phenotype, which differed markedly from the neuronal phenotype observed in cells transduced with a control retrovirus that encoded GFP. Accordingly, the morphology and migration patterns of cells transduced by the two retroviruses are remarkably divergent. These observations support the role of GSK-3β as a cornerstone that regulates the balance between new astocytes/neurons generated in the adult murine DG.</p>","PeriodicalId":11300,"journal":{"name":"Developmental Neurobiology","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2021-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/dneu.22823","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38954156","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Learning-dependent dendritic spine plasticity is impaired in spontaneous autoimmune encephalomyelitis","authors":"Lianyan Huang,&nbsp;Juan J. Lafaille,&nbsp;Guang Yang","doi":"10.1002/dneu.22827","DOIUrl":"10.1002/dneu.22827","url":null,"abstract":"<p>Cognitive impairment is often observed in multiple sclerosis and its animal models, experimental autoimmune encephalomyelitis (EAE). Using mice with immunization-induced EAE, we have previously shown that the stability of cortical synapses is markedly decreased before the clinical onset of EAE. In this study, we examined learning-dependent structural synaptic plasticity in a spontaneous EAE model. Transgenic mice expressing myelin basic protein-specific T cell receptor genes develop EAE spontaneously at around 8 weeks of age. Using in vivo two-photon microscopy, we found that the elimination and formation rates of postsynaptic dendritic spines in somatosensory and motor cortices increased weeks before detectable signs of EAE and remained to be high during the disease onset. Despite the elevated basal spine turnover, motor learning-induced spine formation was reduced in presymptomatic EAE mice, in line with their impaired ability to retain learned motor skills. Additionally, we found a substantial elevation of IFN-γ mRNA in the brain of 4-week-old presymptomatic mice, and treatment of anti-IFN-γ antibody reduced dendritic spine elimination in the cortex. Together, these findings reveal synaptic instability and failure to form new synapses after learning as early brain pathology of EAE, which may contribute to cognitive and behavioral deficits seen in autoimmune diseases.</p>","PeriodicalId":11300,"journal":{"name":"Developmental Neurobiology","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2021-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/dneu.22827","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38883177","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Brain organoids: A promising model to assess oxidative stress-induced central nervous system damage","authors":"Foluwasomi A. Oyefeso,&nbsp;Alysson R. Muotri,&nbsp;Christopher G. Wilson,&nbsp;Michael J. Pecaut","doi":"10.1002/dneu.22828","DOIUrl":"10.1002/dneu.22828","url":null,"abstract":"<p>Oxidative stress (OS) is one of the most significant propagators of systemic damage with implications for widespread pathologies such as vascular disease, accelerated aging, degenerative disease, inflammation, and traumatic injury. OS can be induced by numerous factors such as environmental conditions, lifestyle choices, disease states, and genetic susceptibility. It is tied to the accumulation of free radicals, mitochondrial dysfunction, and insufficient antioxidant protection, which leads to cell aging and tissue degeneration over time. Unregulated systemic increase in reactive species, which contain harmful free radicals, can lead to diverse tissue-specific OS responses and disease. Studies of OS in the brain, for example, have demonstrated how this state contributes to neurodegeneration and altered neural plasticity. As the worldwide life expectancy has increased over the last few decades, the prevalence of OS-related diseases resulting from age-associated progressive tissue degeneration. Unfortunately, vital translational research studies designed to identify and target disease biomarkers in human patients have been impeded by many factors (e.g., limited access to human brain tissue for research purposes and poor translation of experimental models). In recent years, stem cell–derived three-dimensional tissue cultures known as “brain organoids” have taken the spotlight as a novel model for studying central nervous system (CNS) diseases. In this review, we discuss the potential of brain organoids to model the responses of human neural cells to OS, noting current and prospective limitations. Overall, brain organoids show promise as an innovative translational model to study CNS susceptibility to OS and elucidate the pathophysiology of the aging brain.</p>","PeriodicalId":11300,"journal":{"name":"Developmental Neurobiology","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2021-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/dneu.22828","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38945403","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Editorial overview: Microtubules in nervous system development","authors":"Frank Bradke,&nbsp;Antonina Roll-Mecak","doi":"10.1002/dneu.22817","DOIUrl":"10.1002/dneu.22817","url":null,"abstract":"The ability of the nervous system to process information depends on the complex and precise organization of highly ramified and polarized cells such as neurons and glia. The microtubule cytoskeleton is crucial for these cells to attain their elaborate morphologies and to maintain the polarized trafficking of cargo that are required for their communication. This special issue of Developmental Neurobiology brings together reviews and original work focused on how neurons and glia build and maintain their polarized, complex microtubule arrays, how they orchestrate the trafficking of organelles and vesicles, and how they remodel their microtubule cytoskeleton in response to injury. The issue starts with two reviews focused on how microtubule arrays are built and maintained in neurons and glia. These cells pose particular challenges because they need to assemble the microtubule arrays with different morphologies and dynamics in their soma and distal processes and thus rely on decentralized mechanisms of microtubule nucleation. Lüders focuses on recent advances in our understanding of the molecular mechanisms of microtubule nucleation in axons and dendrites to generate arrays with different organization and polarities. This specialization of the microtubule cytoskeleton for transmitting (axon) and receiving (dendrite) information is central to neuronal circuitry (Lüders, 2021). Weigel and colleagues present an overview of microtubule organization of glial cells in the brain– – oligodendrocytes, astrocytes, and microglia, and highlight the many outstanding questions that still remain unanswered in the field: the molecular pathways for microtubule nucleation in distal processes, how trafficking is directed and how these cells build unique, complex structures such as the myelin sheet (Weigel et al., 2021). Trafficking is a key process in neurons, where organelles move along microtubules in the axon and dendrites. In their review, Cheng and Sheng describe how mitochondria are transported in the axon during development and maturation. Interestingly, they highlight recent work about how mitochondria motility changes with aging and present links to neurodegenerative, injured and regenerative stages of the nervous system (Cheng & Sheng, 2021). While we have reached a good understanding of microtubule dynamics, structure and trafficking events in neurons we still know relatively little about the different tubulin isotypes expressed in the developing brain. The article from the Kneussel lab helps to fill this important gap by presenting the tubulin isotypes that are differentially expressed in the developing mouse brain and cultured primary neurons (Hausrat et al., 2021). Next, Moutin and colleagues focus on the role of tubulin posttranslational modifications that is, the tubulin code in regulating microtubule dynamics, neuronal differentiation, plasticity, and transport and highlight the role of the tubulin code in many pathologies of the nervous system (Moutin ","PeriodicalId":11300,"journal":{"name":"Developmental Neurobiology","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2021-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/dneu.22817","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38895098","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}