scholarly journals Regulation of Adult Neurogenesis in Mammalian Brain

2020 ◽  
Vol 21 (14) ◽  
pp. 4869 ◽  
Author(s):  
Maria Victoria Niklison-Chirou ◽  
Massimiliano Agostini ◽  
Ivano Amelio ◽  
Gerry Melino

Adult neurogenesis is a multistage process by which neurons are generated and integrated into existing neuronal circuits. In the adult brain, neurogenesis is mainly localized in two specialized niches, the subgranular zone (SGZ) of the dentate gyrus and the subventricular zone (SVZ) adjacent to the lateral ventricles. Neurogenesis plays a fundamental role in postnatal brain, where it is required for neuronal plasticity. Moreover, perturbation of adult neurogenesis contributes to several human diseases, including cognitive impairment and neurodegenerative diseases. The interplay between extrinsic and intrinsic factors is fundamental in regulating neurogenesis. Over the past decades, several studies on intrinsic pathways, including transcription factors, have highlighted their fundamental role in regulating every stage of neurogenesis. However, it is likely that transcriptional regulation is part of a more sophisticated regulatory network, which includes epigenetic modifications, non-coding RNAs and metabolic pathways. Here, we review recent findings that advance our knowledge in epigenetic, transcriptional and metabolic regulation of adult neurogenesis in the SGZ of the hippocampus, with a special attention to the p53-family of transcription factors.

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Linette Liqi Tan ◽  
Julieta Alfonso ◽  
Hannah Monyer ◽  
Rohini Kuner

AbstractMaladaptive adult neurogenesis in the mammalian brain has been associated with diverse behaviors including disrupted learning, negative mood disorders and psychiatric conditions. However, its functional role in the generation and maintenance of chronic pathological pain has not yet been elucidated. Using an inducible genetic deletion in vivo mouse model, different behavioural paradigms and home cage monitoring systems, we show that an absence of adult neurogenesis does not impact the development of neuropathic injury-induced peripheral nociceptive hypersensitivity, but rather promotes the recovery of pathological pain as well as improves parameters associated with the state of well-being of the injured mice. These results provide a mechanistic insight into the mechanisms of chronic pain and implicate neurogenic processes as a potential therapeutic target for reducing pain and improving the quality of life for patients.


2019 ◽  
Author(s):  
A Docampo-Seara ◽  
S Pereira-Guldrís ◽  
N Sánchez-Farías ◽  
S Mazan ◽  
MA Rodríguez ◽  
...  

AbstractNeurogenesis is a multistep process by which progenitor cells become terminally differentiated neurons. Adult neurogenesis has gathered increasing interest with the aim of developing new cell-based treatments for neurodegenerative diseases in humans. Active sites of adult neurogenesis exist from fish to mammals, although in the adult mammalian brain the number and extension of neurogenic areas is considerably reduced in comparison to non-mammalian vertebrates, and they become mostly reduced to the telencephalon. Much of our understanding in this field is based in studies on mammals and zebrafish, a modern bony fish. The use of the cartilaginous fish Scyliorhinus canicula (representative of basal gnathostomes) as a model expands the comparative framework to a species that shows highly neurogenic activity in the adult brain. In this work, we studied the proliferation pattern in the telencephalon of juvenile and adult specimens of S. canicula by using antibodies against the proliferation marker PCNA. We have characterized proliferating niches by using stem cell markers (Sox2), glial markers (GFAP, BLBP and GS), intermediate progenitor cell markers (Dlx2 and Tbr2) and markers for migrating neuroblasts (DCX). Based in the expression pattern of these markers, we demonstrate the existence of different cell subtypes within the PCNA immunoreactive zones including non-glial stem cells, glial progenitors, intermediate progenitor-like cells and migratory neuroblasts, which were widely distributed in the ventricular zone of the pallium, suggesting that the main progenitor types that constitute the neurogenic niche in mammals are already present in cartilaginous fishes.


2007 ◽  
Vol 363 (1489) ◽  
pp. 101-122 ◽  
Author(s):  
Jan Kaslin ◽  
Julia Ganz ◽  
Michael Brand

Post-embryonic neurogenesis is a fundamental feature of the vertebrate brain. However, the level of adult neurogenesis decreases significantly with phylogeny. In the first part of this review, a comparative analysis of adult neurogenesis and its putative roles in vertebrates are discussed. Adult neurogenesis in mammals is restricted to two telencephalic constitutively active zones. On the contrary, non-mammalian vertebrates display a considerable amount of adult neurogenesis in many brain regions. The phylogenetic differences in adult neurogenesis are poorly understood. However, a common feature of vertebrates (fish, amphibians and reptiles) that display a widespread adult neurogenesis is the substantial post-embryonic brain growth in contrast to birds and mammals. It is probable that the adult neurogenesis in fish, frogs and reptiles is related to the coordinated growth of sensory systems and corresponding sensory brain regions. Likewise, neurons are substantially added to the olfactory bulb in smell-oriented mammals in contrast to more visually oriented primates and songbirds, where much fewer neurons are added to the olfactory bulb. The second part of this review focuses on the differences in brain plasticity and regeneration in vertebrates. Interestingly, several recent studies show that neurogenesis is suppressed in the adult mammalian brain. In mammals, neurogenesis can be induced in the constitutively neurogenic brain regions as well as ectopically in response to injury, disease or experimental manipulations. Furthermore, multipotent progenitor cells can be isolated and differentiated in vitro from several otherwise silent regions of the mammalian brain. This indicates that the potential to recruit or generate neurons in non-neurogenic brain areas is not completely lost in mammals. The level of adult neurogenesis in vertebrates correlates with the capacity to regenerate injury, for example fish and amphibians exhibit the most widespread adult neurogenesis and also the greatest capacity to regenerate central nervous system injuries. Studying these phenomena in non-mammalian vertebrates may greatly increase our understanding of the mechanisms underlying regeneration and adult neurogenesis. Understanding mechanisms that regulate endogenous proliferation and neurogenic permissiveness in the adult brain is of great significance in therapeutical approaches for brain injury and disease.


2021 ◽  
Author(s):  
Dylan J Terstege ◽  
Kwaku Addo-Osafo ◽  
Gordon Campbell Teskey ◽  
Jonathan R Epp

Adult neurogenesis has primarily been examined in two key regions in the mammalian brain, the subgranular zone of the hippocampus and the subventricular zone. The proliferation and integration of newly generated neurons has been observed widely in adult mammalian species including the human hippocampus. Recent high-profile studies have suggested however, that this process is considerably reduced in humans, occurring in children but declining rapidly and nearly completely in the adult brain. In comparison, rodent studies also show age-related decline but a greater degree of proliferation of new neurons in adult animals. Here, we examine whether differences in tissue fixation, rather than biological difference in human versus rodent studies might account for the diminished levels of neurogenesis sometimes observed in the human brain. To do so we analyzed neurogenesis in the hippocampus of rats that were either perfusion-fixed or the brains extracted and immersion-fixed at various post-mortem intervals. We observed an interaction between animal age and the time delay between death and tissue fixation. While similar levels of neurogenesis were observed in young rats regardless of fixation, older rats had significantly fewer labeled neurons when fixation was not immediate. Furthermore, the morphological detail of the labeled neurons was significantly reduced in the delayed fixation conditions at all ages. This study highlights critical concerns that must be considered when using post-mortem tissue to quantify adult neurogenesis.


2005 ◽  
Vol 85 (2) ◽  
pp. 523-569 ◽  
Author(s):  
Djoher Nora Abrous ◽  
Muriel Koehl ◽  
Michel Le Moal

The discovery that the adult mammalian brain creates new neurons from pools of stemlike cells was a breakthrough in neuroscience. Interestingly, this particular new form of structural brain plasticity seems specific to discrete brain regions, and most investigations concern the subventricular zone (SVZ) and the dentate gyrus (DG) of the hippocampal formation (HF). Overall, two main lines of research have emerged over the last two decades: the first aims to understand the fundamental biological properties of neural stemlike cells (and their progeny) and the integration of the newly born neurons into preexisting networks, while the second focuses on understanding its relevance in brain functioning, which has been more extensively approached in the DG. Here, we propose an overview of the current knowledge on adult neurogenesis and its functional relevance for the adult brain. We first present an analysis of the methodological issues that have hampered progress in this field and describe the main neurogenic sites with their specificities. We will see that despite considerable progress, the levels of anatomic and functional integration of the newly born neurons within the host circuitry have yet to be elucidated. Then the intracellular mechanisms controlling neuronal fate are presented briefly, along with the extrinsic factors that regulate adult neurogenesis. We will see that a growing list of epigenetic factors that display a specificity of action depending on the neurogenic site under consideration has been identified. Finally, we review the progress accomplished in implicating neurogenesis in hippocampal functioning under physiological conditions and in the development of hippocampal-related pathologies such as epilepsy, mood disorders, and addiction. This constitutes a necessary step in promoting the development of therapeutic strategies.


2020 ◽  
Vol 3 (2) ◽  
pp. 216-242 ◽  
Author(s):  
Mayuri Shukla ◽  
Areechun Sotthibundhu ◽  
Piyarat Govitrapong

The revelation of adult brain exhibiting neurogenesis has established that the brain possesses great plasticity and that neurons could be spawned in the neurogenic zones where hippocampal adult neurogenesis attributes to learning and memory processes. With strong implications in brain functional homeostasis, aging and cognition, various aspects of adult neurogenesis reveal exuberant mechanistic associations thereby further aiding in facilitating the therapeutic approaches regarding the development of neurodegenerative processes in Alzheimer’s Disease (AD). Impaired neurogenesis has been significantly evident in AD with compromised hippocampal function and cognitive deficits. Melatonin the pineal indolamine augments neurogenesis and has been linked to AD development as its levels are compromised with disease progression. Here, in this review, we discuss and appraise the mechanisms via which melatonin regulates neurogenesis in pathophysiological conditions which would unravel the molecular basis in such conditions and its role in endogenous brain repair. Also, its components as key regulators of neural stem and progenitor cell proliferation and differentiation in the embryonic and adult brain would aid in accentuating the therapeutic implications of this indoleamine in line of prevention and treatment of AD.   


Author(s):  
Sarah F. Beul ◽  
Alexandros Goulas ◽  
Claus C. Hilgetag

AbstractStructural connections between cortical areas form an intricate network with a high degree of specificity. Many aspects of this complex network organization in the adult mammalian cortex are captured by an architectonic type principle, which relates structural connections to the architectonic differentiation of brain regions. In particular, the laminar patterns of projection origins are a prominent feature of structural connections that varies in a graded manner with the relative architectonic differentiation of connected areas in the adult brain. Here we show that the architectonic type principle is already apparent for the laminar origins of cortico-cortical projections in the immature cortex of the macaque monkey. We find that prenatal and neonatal laminar patterns correlate with cortical architectonic differentiation, and that the relation of laminar patterns to architectonic differences between connected areas is not substantially altered by the complete loss of visual input. Moreover, we find that the degree of change in laminar patterns that projections undergo during development varies in proportion to the relative architectonic differentiation of the connected areas. Hence, it appears that initial biases in laminar projection patterns become progressively strengthened by later developmental processes. These findings suggest that early neurogenetic processes during the formation of the brain are sufficient to establish the characteristic laminar projection patterns. This conclusion is in line with previously suggested mechanistic explanations underlying the emergence of the architectonic type principle and provides further constraints for exploring the fundamental factors that shape structural connectivity in the mammalian brain.


Biomolecules ◽  
2020 ◽  
Vol 11 (1) ◽  
pp. 24
Author(s):  
Eva Pokorná ◽  
Tomáš Hluska ◽  
Petr Galuszka ◽  
H. Tucker Hallmark ◽  
Petre I. Dobrev ◽  
...  

Cytokinins (CKs) are a class of phytohormones affecting many aspects of plant growth and development. In the complex process of CK homeostasis in plants, N-glucosylation represents one of the essential metabolic pathways. Its products, CK N7- and N9-glucosides, have been largely overlooked in the past as irreversible and inactive CK products lacking any relevant physiological impact. In this work, we report a widespread distribution of CK N-glucosides across the plant kingdom proceeding from evolutionary older to younger plants with different proportions between N7- and N9-glucosides in the total CK pool. We show dramatic changes in their profiles as well as in expression levels of the UGT76C1 and UGT76C2 genes during Arabidopsis ontogenesis. We also demonstrate specific physiological effects of CK N-glucosides in CK bioassays including their antisenescent activities, inhibitory effects on root development, and activation of the CK signaling pathway visualized by the CK-responsive YFP reporter line, TCSv2::3XVENUS. Last but not least, we present the considerable impact of CK N7- and N9-glucosides on the expression of CK-related genes in maize and their stimulatory effects on CK oxidase/dehydrogenase activity in oats. Our findings revise the apparent irreversibility and inactivity of CK N7- and N9-glucosides and indicate their involvement in CK evolution while suggesting their unique function(s) in plants.


2021 ◽  
Vol 22 (14) ◽  
pp. 7450
Author(s):  
Citlalli Netzahualcoyotzi ◽  
Luis Miguel Rodríguez-Serrano ◽  
María Elena Chávez-Hernández ◽  
Mario Humberto Buenrostro-Jáuregui

The endocannabinoid system (ECS) is a crucial modulatory system in which interest has been increasing, particularly regarding the regulation of behavior and neuroplasticity. The adolescent–young adulthood phase of development comprises a critical period in the maturation of the nervous system and the ECS. Neurogenesis occurs in discrete regions of the adult brain, and this process is linked to the modulation of some behaviors. Since marijuana (cannabis) is the most consumed illegal drug globally and the highest consumption rate is observed during adolescence, it is of particular importance to understand the effects of ECS modulation in these early stages of adulthood. Thus, in this article, we sought to summarize recent evidence demonstrating the role of the ECS and exogenous cannabinoid consumption in the adolescent–young adulthood period; elucidate the effects of exogenous cannabinoid consumption on adult neurogenesis; and describe some essential and adaptive behaviors, such as stress, anxiety, learning, and memory. The data summarized in this work highlight the relevance of maintaining balance in the endocannabinoid modulatory system in the early and adult stages of life. Any ECS disturbance may induce significant modifications in the genesis of new neurons and may consequently modify behavioral outcomes.


Author(s):  
Xiaoping Huang ◽  
Hongyu Zhang ◽  
Qiang Wang ◽  
Rong Guo ◽  
Lingxia Wei ◽  
...  

Abstract Key message This study showed the systematic identification of long non-coding RNAs (lncRNAs) involving in flag leaf senescence of rice, providing the possible lncRNA-mRNA regulatory relationships and lncRNA-miRNA-mRNA ceRNA networks during leaf senescence. Abstract LncRNAs have been reported to play crucial roles in diverse biological processes. However, no systematic identification of lncRNAs associated with leaf senescence in plants has been studied. In this study, a genome-wide high throughput sequencing analysis was performed using rice flag leaves developing from normal to senescence. A total of 3953 lncRNAs and 38757 mRNAs were identified, of which 343 lncRNAs and 9412 mRNAs were differentially expressed. Through weighted gene co-expression network analysis (WGCNA), 22 continuously down-expressed lncRNAs targeting 812 co-expressed mRNAs and 48 continuously up-expressed lncRNAs targeting 1209 co-expressed mRNAs were considered to be significantly associated with flag leaf senescence. Gene Ontology results suggested that the senescence-associated lncRNAs targeted mRNAs involving in many biological processes, including transcription, hormone response, oxidation–reduction process and substance metabolism. Additionally, 43 senescence-associated lncRNAs were predicted to target 111 co-expressed transcription factors. Interestingly, 8 down-expressed lncRNAs and 29 up-expressed lncRNAs were found to separately target 12 and 20 well-studied senescence-associated genes (SAGs). Furthermore, analysis on the competing endogenous RNA (CeRNA) network revealed that 6 down-expressed lncRNAs possibly regulated 51 co-expressed mRNAs through 15 miRNAs, and 14 up-expressed lncRNAs possibly regulated 117 co-expressed mRNAs through 21 miRNAs. Importantly, by expression validation, a conserved miR164-NAC regulatory pathway was found to be possibly involved in leaf senescence, where lncRNA MSTRG.62092.1 may serve as a ceRNA binding with miR164a and miR164e to regulate three transcription factors. And two key lncRNAs MSTRG.31014.21 and MSTRG.31014.36 also could regulate the abscisic-acid biosynthetic gene BGIOSGA025169 (OsNCED4) and BGIOSGA016313 (NAC family) through osa-miR5809. The possible regulation networks of lncRNAs involving in leaf senescence were discussed, and several candidate lncRNAs were recommended for prior transgenic analysis. These findings will extend the understanding on the regulatory roles of lncRNAs in leaf senescence, and lay a foundation for functional research on candidate lncRNAs.


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