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(a) Hormonal regulation of neurogenesis in the mammalian brain. Subgranular layer, SGL; subventricular zone, SVZ; lateral ventricle, LV. (b) Current view of the regulation of adult neurogenesis.
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Presumably, the 'hard-wired' neuronal circuitry of the adult brain dissuades addition of new neurons, which could potentially disrupt existing circuits. This is borne out by the fact that, in general, new neurons are not produced in the mature brain. However, recent studies have established that the adult brain does maintain discrete regions of neu...
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Adult neurogenesis, a striking form of neural plasticity, is involved in the modulation of social stimuli driving reproduction. Previous studies on adult neurogenesis have shown that this process is significantly modulated around puberty in female mice. Puberty is a critical developmental period triggered by increased secretion of the gonadotropin...
It has been accepted that new neurons are added to the olfactory bulb and the hippocampal dentate gyrus throughout life in the healthy adult mammalian brain. Recent studies have clarified that brain insult raises the proliferation of neural stem cells/neural progenitor cells existing in the subventricular zone and the subgranular zone, which become...
Adult neurogenesis is a lifelong process that occurs in two main neurogenic niches of the brain, namely in the subventricular zone (SVZ) of the lateral ventricles and in the subgranular zone (SGZ) of the dentate gyrus (DG) in the hippocampus. In the 1960s, studies on adult neurogenesis have been hampered by the lack of established phenotypic marker...
Neurogenesis, the production of new neurons, occurs in two specialized niches in the adult brain, the subgranular zone (SGZ) of the dentate gyrus and the subventricular zone (SVZ) adjacent to the lateral ventricles. In the SGZ, neural stem cells (NSCs) give rise to glutamatergic granule neurons that integrate into the granule cell layer. In the SVZ...
Spinal cord injury (SCI) triggers a complex cellular response at the injury site, leading to the formation of a dense scar tissue. Despite this local tissue remodeling, the consequences of SCI at the cellular level in distant rostral sites (i.e., brain), remain unknown. In this study, we asked whether cervical SCI could alter cell dynamics in neuro...
Citations
... On the other hand, central nerve cell restoration involves sprouting, a process wherein new axons, dendrites, and synapses grow from the intact central nerve cell body. Neurogenesis, the growth of new neurons, is possible if the neurons retain some of their multipotent neural stem/progenitor cell population, especially near the injury site [33]. [8], 2017 ...
Unlike central nervous system injuries, peripheral nerve injuries (PNIs) are often characterized by more or less successful axonal regeneration. However, structural and functional recovery is a senile process involving multifaceted cellular and molecular processes. The contemporary treatment options are limited, with surgical intervention as the gold-standard method; however, each treatment option has its associated limitations, especially when the injury is severe with a large gap. Recent advancements in cell-based therapy and cell-free therapy approaches using stem cell-derived soluble and insoluble components of the cell secretome are fast-emerging therapeutic approaches to treating acute and chronic PNI. The recent pilot study is a leap forward in the field, which is expected to pave the way for more enormous, systematic, and well-designed clinical trials to assess the therapeutic efficacy of mesenchymal stem cell-derived exosomes as a bio-drug either alone or as part of a combinatorial approach, in an attempt synergize the best of novel treatment approaches to address the complexity of the neural repair and regeneration.
... We used cell2location for deconvolution and obtaining the cell type-specific expression information, with which we further estimated the pseudo-time trajectory using slingshot in the mature neurons (Fig. 3E). The inferred neuronal trajectory captures the key features of the rostral migratory stream, a migration path of newly generated neuroblasts that migrate from the sub ventricular zone of the lateral ventricles into the OB [51]. In particular, the pseudo-time of OB (domain 8) is significantly higher than that of the lateral ventricle (domain 9) (t = 117.11, ...
Background
Spatial resolved transcriptomics (SRT) encompasses a rapidly developing set of technologies that enable the measurement of gene expression in tissue while retaining spatial localization information. SRT technologies and the enabled SRT studies have provided unprecedent insights into the structural and functional underpinnings of complex tissues. As SRT technologies have advanced and an increasing number of SRT studies have emerged, numerous sophisticated statistical and computational methods have been developed to facilitate the analysis and interpretation of SRT data. However, despite the growing popularity of SRT studies and the widespread availability of SRT analysis methods, analysis of large-scale and complex SRT datasets remains challenging and not easily accessible to researchers with limited statistical and computational backgrounds.
Results
Here, we present SRT-Server, the first webserver designed to carry out comprehensive SRT analyses for a wide variety of SRT technologies while requiring minimal prior computational knowledge. Implemented with cutting-edge web development technologies, SRT-Server is user-friendly and features multiple analytic modules that can perform a range of SRT analyses. With a flowchart-style interface, these different analytic modules on the SRT-Server can be dragged into the main panel and connected to each other to create custom analytic pipelines. SRT-Server then automatically executes the desired analyses, generates corresponding figures, and outputs results—all without requiring prior programming knowledge. We demonstrate the advantages of SRT-Server through three case studies utilizing SRT data collected from two common platforms, highlighting its versatility and values to researchers with varying analytic expertise.
Conclusions
Overall, SRT-Server presents a user-friendly, efficient, effective, secure, and expandable solution for SRT data analysis, opening new doors for researchers in the field. SRT-Server is freely available at https://spatialtranscriptomicsanalysis.com/.
... The therapeutic effects of stem cells are not limited to their ability to replace damaged or dead cells and tissues. They have also been shown to provide a supportive microenvironment suitable for neurogenesis [14,15], neurotrophic factor release [16], and mitochondrial transfer [17,18]. ...
Neurological injuries can have numerous debilitating effects on functional status including sensorimotor deficits, cognitive impairment, and behavioral symptoms. Despite the disease burden, treatment options remain limited. Current pharmacological interventions are targeted at symptom management but are ineffective in reversing ischemic brain damage. Stem cell therapy for ischemic brain injury has shown promising preclinical and clinical results and has attracted attention as a potential therapeutic option. Various stem cell sources (embryonic, mesenchymal/bone marrow, and neural stem cells) have been investigated. This review provides an overview of the advances made in our understanding of the various types of stem cells and progress made in the use of these stem cells for the treatment of ischemic brain injuries. In particular, the use of stem cell therapy in global cerebral ischemia following cardiac arrest and in focal cerebral ischemia after ischemic stroke are discussed. The proposed mechanisms of stem cells' neuroprotective effects in animal models (rat/mice, pig/swine) and other clinical studies, different routes of administration (intravenous/intra-arterial/intracerebroventricular/intranasal/intraperitoneal/intracranial) and stem cell preconditioning are discussed. Much of the promising data on stem cell therapies after ischemic brain injury remains in the experimental stage and several limitations remain unsettled. Future investigation is needed to further assess the safety and efficacy and to overcome the remaining obstacles.
... Further delivery to the CNS occurs through the rostral migratory stream (RMS). The RMS is a specialized migratory route along which neuronal precursors that originate in the subventricular zone of the brain migrate to reach the olfactory bulb (28). Previous studies have demonstrated that intranasal administration of a fluorescent tracer allows agents to be distributed throughout the entire brain including the olfactory bulb, cortex, and cerebellum (29). ...
The expanding field of precision gene editing using CRISPR/Cas9 has demonstrated its potential as a transformative technology in the treatment of various diseases. However, whether this genome-editing tool could be used to modify neural circuits in the central nervous system (CNS), which are implicated in complex behavioral traits, remains uncertain. In this study, we demonstrate the feasibility of noninvasive, intranasal delivery of adeno-associated virus serotype 9 (AAV9) vectors containing CRISPR/Cas9 cargo within the CNS resulting in modification of the HTR2A receptor gene. In vitro, exposure to primary mouse cortical neurons to AAV9 vectors targeting the HT2RA gene led to a concentration-dependent decrease in spontaneous electrical activity following multielectrode array (MEA) analysis. In vivo, at 5 weeks postintranasal delivery in mice, analysis of brain samples revealed single base pair deletions and nonsense mutations, leading to an 8.46-fold reduction in mRNA expression and a corresponding 68% decrease in the 5HT-2A receptor staining. Our findings also demonstrate a significant decrease in anxiety-like behavior in treated mice. This study constitutes the first successful demonstration of a noninvasive CRISPR/Cas9 delivery platform, capable of bypassing the blood–brain barrier and enabling modulation of neuronal 5HT-2A receptor pathways. The results of this study targeting the HTR2A gene provide a foundation for the development of innovative therapeutic strategies for a broad range of neurological disorders, including anxiety, depression, attentional deficits, and cognitive dysfunction.
... It is believed that the process of formation of new neurons goes on throughout the whole life period, but its intensity significantly decreases with age [2]. Neurogenesis in the adult brain takes place in neurogenic niches, which are located in the ventricular-subventricular zone (V-SVZ) and in the subgranular zone (SGZ) of the gyrus dentatus (DG) [3,4]. DG and hippocampus are the parts of the hippocampal formation, which plays an essential role in learning and memory. ...
Hippocampus is one of the neurogenic zones where adult neurogenesis takes place. This process is quite complex and has a multicomponent regulation. A family of G protein-coupled trace amine-associated receptors (TAARs) was discovered only in 2001, and most of them (TAAR2-TAAR9) were primarily considered olfactory. Recent studies have shown, however, that they are also expressed in the mouse brain, particularly in limbic formations, and can play a role in the regulation of emotional behaviors. The observations in knockout mice indicate that at least two members of the family, TAAR2 and TAAR5, have an impact on the regulation of adult neurogenesis. In the present study, we analyzed the expression of TAARs in the murine and human hippocampus using public RNAseq datasets. Our results indicate a low but detectable level of certain TAARs expression in the hippocampal cells in selected high-quality transcriptomic datasets from both mouse and human samples. At the same time, we observed the difference between humans, where TAAR6 expression was the highest, and murine samples, where TAAR1, TAAR2, TAAR3, TAAR4 and TAAR5 are more pronouncedly expressed. These observations provide further support to the data gained in knockout mice, indicating a role of TAARs in the regulation of adult neurogenesis in the hippocampus.
... NSCs produce neuroblasts that mature to neurons involved in the sense of smell, memory and other cognitive functions [43,44]. Therefore, the transplantation of NSCs in patients with AD signifies the use for cell replacement therapy [45]. ...
Alzheimer’s disease (AD) is known as an age-related neurodegenerative disease where progressive loss of memory associated with cognition defects has been noticed. Molecular analysis of AD revealed the formation of aggregated amyloid-β protein and hyper phosphorylated tau tangles at the synaptic circuit, which causes the loss of neuronal communication.
... a, Head of a mouse showing the location of the brain and the rostral migratory stream (RMS) (in red) along which newly generated neuroblasts migrate from the subventricular zone of the lateral ventricle (LV) into the olfactory bulb (OB). b, Newly generated neuroblasts begin their migration at the lateral ventricle, continue along the RMS, and arrive in the olfactory bulb, where mature interneuron populations are generated.Figure adaptedwith permission from ref.223 , Biomed Central Ltd. ...
Biological organisms learn from interactions with their environment throughout their lifetime. For artificial systems to successfully act and adapt in the real world, it is desirable to similarly be able to learn on a continual basis. This challenge is known as lifelong learning, and remains to a large extent unsolved. In this Perspective article, we identify a set of key capabilities that artificial systems will need to achieve lifelong learning. We describe a number of biological mechanisms, both neuronal and non-neuronal, that help explain how organisms solve these challenges, and present examples of biologically inspired models and biologically plausible mechanisms that have been applied to artificial systems in the quest towards development of lifelong learning machines. We discuss opportunities to further our understanding and advance the state of the art in lifelong learning, aiming to bridge the gap between natural and artificial intelligence. It is an outstanding challenge to develop intelligent machines that can learn continually from interactions with their environment, throughout their lifetime. Kudithipudi et al. review neuronal and non-neuronal processes in organisms that address this challenge and discuss pathways to developing biologically inspired approaches for lifelong learning machines.
... Males have greater predisposition to olfactory dysfunction because they have higher livelihood of exposure to harmful agents.in adddition estrogen and progesterone might have favourable impacts in peripheral or central olfactory region stem cells that could delay olfactory decline in women [36,37] moreover neural function has propensity to diminish more rapidly in mens as compared to womens [38,39]. ...
Anosmia (loss of smell) and Ageusia (loss of taste) are newly presenting independent symptoms in association with multiple symptoms such as Fever, Dry cough and Breathlessness in COVID 19 Patients.The Study of aims is to estimate Prevalence of Anosmia & Ageusia in Confirmed Covid 19 cases and to assess their Recovery rates. A Study conducted between June 2020 and September 2020 at a tertiary care COVID Dedicated hospital. Total 200 patients with age group 12–70 years Confirmed COVID 19 Positive Patients using RTPCR having mild to moderate symptoms were included. Patients were examined Clinically alongwith all safety measures to analyse prevalence & estimate their recoveries from sensory impairement using 10 item based DyNaCHRON questionnaire(concerned with taste and smell) at 10th, 14th & 21st Day. Out of 200 patients, Prevalence of Isolated Ageusia is 7%, Isolated Anosmia 4.5% and with Anosmia and Ageusia 4%. Complete Recovery regained in Ageusia within 14 days, while Rest all patients of Anosmia and both (Anosmia and Ageusia) within 21 days, Except 2 patients where long term Anosmia persists. Newly onset Anosmia and Ageusia are common in early stages of Covid 19 disease. They are Prevalent in mild to moderate symptomatic form of Diseases. Recovery in most cases is rapid and complete.Early Screening tests performed in suspected COVID 19 patients with loss of taste and smell sensation allows early diagnosis and treatment.
... Integration of the microenvironmental signals that regulate activity of NSCs and TAPs (herein, referred to collectively as neural stem/progenitor cells, NSPCs) is mediated by a limited number of intracellular signaling pathways (Lennington et al., 2003;Faigle and Song, 2013). It is modulation of these intracellular signaling pathways that ultimately controls NSPC survival, proliferation and differentiation (Lim and Alvarez-Buylla, 2016;Cutler and Kokovay, 2020). ...
The ventricular-subventricular zone (V-SVZ) is the principal neurogenic niche in the adult mammalian forebrain. Neural stem/progenitor cell (NSPC) activity within the V-SVZ is controlled by numerous of extrinsic factors, whose downstream effects on NSPC proliferation, survival and differentiation are transduced via a limited number of intracellular signaling pathways. Here, we investigated the relationship between age-related changes in NSPC output and activity of signaling pathways downstream of the epidermal growth factor receptor (EGFR), a major regulator of NSPC activity. Biochemical experiments indicated that age-related decline of NSPC activity in vivo is accompanied by selective deficits amongst various EGFR-induced signal pathways within the V-SVZ niche. Pharmacological loss-of-function signaling experiments with cultured NSPCs revealed both overlap and selectivity in the biological functions modulated by the EGFR-induced PI3K/AKT, MEK/ERK and mTOR signaling modules. Specifically, while all three modules promoted EGFR-mediated NSPC proliferation, only mTOR contributed to NSPC survival and only MEK/ERK repressed NSPC differentiation. Using a gain-of-function in vivo genetic approach, we electroporated a constitutively active EGFR construct into a subpopulation of quiescent, EGFR-negative neural stem cells (qNSCs); this ectopic activation of EGFR signaling enabled qNSCs to divide in 3-month-old early adult mice, but not in mice at middle-age or carrying familial Alzheimer disease mutations. Thus, (i) individual EGFR-induced signaling pathways have dissociable effects on NSPC proliferation, survival, and differentiation, (ii) activation of EGFR signaling is sufficient to stimulate qNSC cell cycle entry during early adulthood, and (iii) the proliferative effects of EGFR-induced signaling are dominantly overridden by anti-proliferative signals associated with aging and Alzheimer’s disease.
... Males have greater predisposition to olfactory dysfunction because they have the higher likelihood of exposure to harmful agents. In addition, estrogen and progesterone might have favorable impacts in peripheral or central olfactory region stem cells, that could delay olfactory decline in women [29,30]. Moreover, neural function has propensity to diminish more rapidly in men as compared to women [31,32]. ...
Aim and objectives:
To describe the prevalence and characteristics of olfactory dysfunction (OD) in patients with laboratory-confirmed COVID-19 infection.
Materials and methods:
This monocentric study was performed at Chest Diseases Hospital during the COVID-19 pandemic and all patients testing positive for COVID-19 over a 5-month period (April to August 2020) were recruited. Detailed history was elicited from subjects and all patients were inquired about olfactory dysfunction (OD). Patients with olfactory dysfunction were asked to complete olfactory questionnaires based on the short version of the Questionnaire of Olfactory Disorders-Negative Statements (sQOD-NS).
Results:
655 patients with mild to moderate COVID-19 infection were included in the study. The prevalence rate of olfactory dysfunction was 18.47% (n = 121) with contribution of 11.60% (n = 76) and 6.87% (n = 45) from anosmia and hyposmia respectively, thereby suggesting olfactory dysfunction to be a significant clinical feature in COVID-19 patients. Males were significantly more affected by olfactory dysfunctions than females. Anosmic patients had significantly reduced sQOD-NS results as compared to hyposmic patients (significant at P < 0.05). The mean duration of OD was 7.7 days (± 4.3) and >90% patients in our study showed resolution within 14 days.
Conclusion:
The early recognition of olfactory dysfunction should help to screen, identify and thereby quickly isolate mildly symptomatic COVID-19 patients from the general population and the existence of these dysfunctions may well be a prognostic factor in the course of the disease.
