scholarly journals New neurons in old brains: A cautionary tale for the analysis of neurogenesis in post-mortem tissue.

2021 ◽  
Author(s):  
Dylan J Terstege ◽  
Kwaku Addo-Osafo ◽  
Gordon Campbell Teskey ◽  
Jonathan R Epp
Keyword(s):  
Adult Neurogenesis ◽  
Mammalian Species ◽  
Adult Brain ◽  
Mammalian Brain ◽  
Tissue Fixation ◽  
Post Mortem ◽  
Biological Difference ◽  
High Profile ◽  
Age Related ◽  
Morphological Detail

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.

scholarly journals Adult neurogenesis in natural populations

2001 ◽  
Vol 79 (4) ◽  
pp. 297-302 ◽  
Author(s):  
R Boonstra ◽  
L Galea ◽  
S Matthews ◽  
J M Wojtowicz
Keyword(s):  
Adult Neurogenesis ◽  
Mammalian Species ◽  
Natural Populations ◽  
Hippocampal Neurogenesis ◽  
Adult Brain ◽  
Biologically Relevant ◽  
Evolutionarily Conserved ◽  
Functional Consequences ◽  
Song Production ◽  
And Function

The dogma that the adult brain produces no new neurons has been overturned, but the critics are still asking, so what? Is adult neurogenesis a biologically relevant phenomenon, or is it perhaps harmful because it disrupts the existing neuronal circuitry? Considering that the phenomenon is evolutionarily conserved in all mammalian species examined to date and that its relevance has been well documented in non-mammalian species, it seems self-evident that neurogenesis in adult mammals must have a role. In birds, it has been established that neurogenesis varies dramatically with seasonal changes in song production. In chickadees, the learning behaviour related to finding stored food is also correlated with seasonal adult neurogenesis. Such studies are still nonexistent in mammals, but the related evidence suggests that neurogenesis does vary seasonally in hamsters and shows sexual differences in meadow voles. To promote studies on natural populations asking fundamental questions of the purpose and function of neurogenesis, we organized a Workshop on "Hippocampal Neurogenesis in Natural Populations" in Toronto in May 2000. The Workshop highlighted recent discoveries in neurogenesis from the lab, and focused on its functional consequences. The consensus at the Workshop was that demonstration of a role for neurogenesis in natural behaviours will ultimately be essential if we are to understand the purpose and function of neurogenesis in humans.Key words: neurogenesis, hippocampus, dentate gyrus, learning, memory, wild population.

scholarly journals Neurogenesis in the adult brain functionally contributes to the maintenance of chronic neuropathic pain

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Linette Liqi Tan ◽  
Julieta Alfonso ◽  
Hannah Monyer ◽  
Rohini Kuner
Keyword(s):  
Adult Neurogenesis ◽  
Negative Mood ◽  
Well Being ◽  
Adult Brain ◽  
Mammalian Brain ◽  
Chronic Neuropathic Pain ◽  
Pathological Pain ◽  
Psychiatric Conditions

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.

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
Keyword(s):  
Transcription Factors ◽  
Adult Neurogenesis ◽  
Metabolic Pathways ◽  
Metabolic Regulation ◽  
Adult Brain ◽  
Mammalian Brain ◽  
P53 Family ◽  
Intrinsic Factors ◽  
The Past ◽  
Non Coding Rnas

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.

scholarly journals Characterization of neurogenic niches in the telencephalon of juvenile and adult sharks

2019 ◽  
Author(s):  
A Docampo-Seara ◽  
S Pereira-Guldrís ◽  
N Sánchez-Farías ◽  
S Mazan ◽  
MA Rodríguez ◽  
...  
Keyword(s):  
Adult Neurogenesis ◽  
Active Sites ◽  
Ventricular Zone ◽  
Adult Brain ◽  
Mammalian Brain ◽  
Stem Cell Markers ◽  
Cell Markers ◽  
Neurogenic Niche ◽  
Glial Progenitors ◽  
Multistep Process

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.

scholarly journals Proliferation, neurogenesis and regeneration in the non-mammalian vertebrate brain

2007 ◽  
Vol 363 (1489) ◽  
pp. 101-122 ◽  
Author(s):  
Jan Kaslin ◽  
Julia Ganz ◽  
Michael Brand
Keyword(s):  
Olfactory Bulb ◽  
Adult Neurogenesis ◽  
Brain Plasticity ◽  
Brain Regions ◽  
Adult Brain ◽  
Mammalian Brain ◽  
Embryonic Neurogenesis ◽  
Vertebrate Brain ◽  
Multipotent Progenitor Cells

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.

Adult Neurogenesis: From Precursors to Network and Physiology

2005 ◽  
Vol 85 (2) ◽  
pp. 523-569 ◽  
Author(s):  
Djoher Nora Abrous ◽  
Muriel Koehl ◽  
Michel Le Moal
Keyword(s):  
Adult Neurogenesis ◽  
Brain Plasticity ◽  
Current Knowledge ◽  
Hippocampal Formation ◽  
Functional Integration ◽  
Brain Regions ◽  
Biological Properties ◽  
Adult Brain ◽  
Mammalian Brain ◽  
Extrinsic Factors

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.

ADULT NEUROGENESIS: ALTERATIONS WITH AGING AND ALZHEIMER’S DISEASE DEVELOPMENT

2021 ◽  
pp. 1080-1087
Author(s):  
А. О. Бурняшева ◽  
Н. А. Стефанова ◽  
Е. А. Рудницкая
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Adult Neurogenesis ◽  
Neurodegenerative Disorder ◽  
Brain Plasticity ◽  
The Elderly ◽  
Adult Brain ◽  
Molecular Control ◽  
Neurogenic Niche ◽  
Age Related

Нейрогенез в головном мозге взрослого организма - один из важнейших механизмов пластичности, который проявляется увеличением числа клеток, участвующих в структурной перестройке нейрональных сетей и формированием синапсов, и способствует увеличению функциональных возможностей головного мозга. С возрастом и при развитии нейродегенеративных расстройств происходит нарушение микроокружения нейрогенной ниши, ослабление контроля и, как следствие, значительное снижение нейрогенеза, что, в свою очередь, может способствовать ухудшению когнитивных способностей и развитию деменции. Наиболее распространённой сенильной деменцией является болезнь Альцгеймера - неизлечимое заболевание нейродегенеративной природы, при котором одними из первых поражаются гиппокамп и энторинальная кора - ключевые нейрогенные ниши зрелого головного мозга, что приводит к нарушению нейрогенеза и способствует дальнейшей прогрессии дегенеративных процессов. На сегодняшний день механизмы, лежащие в основе сопровождающих развитие болезни Альцгеймера изменений нейрогенеза, остаются до конца неясными и являются предметом интенсивного изучения исследователей во всём мире как потенциальная мишень для коррекции патологических изменений. Adult neurogenesis is one of the key mechanisms of the brain plasticity. Increase in the number of cells participating in the rearrangement of the neuronal circuits and synaptic formation facilitates the increase of brain’s functional capacity. However, aging as well as neurodegenerative disorders lead to the disruption of the neurogenic niche microenvironment and the loss of molecular control, which in turn results in the significant decline of the neurogenesis. These events may contribute to the cognitive decline and the consequent development of dementia. Alzheimer’s disease is a progressive incurable age-related neurodegenerative disorder in the elderly and the most prevalent cause of dementia. Hippocampus and entorhinal cortex are the key neurogenic niches in the adult brain and one of the most vulnerable brain areas during the development of Alzheimer’s disease. Thus, neurodegeneration associated with the development of Alzheimer’s disease affects adult neurogenesis. However, to date the mechanisms underlying this connection are unclear, and the investigation of these mechanisms is a promising strategy to find the approaches to correct the Alzheimer’s disease pathology.

scholarly journals Activation of autophagy ameliorates age-related neurogenesis decline and neurodysfunction in adult mice

2021 ◽  
Author(s):  
na yang ◽  
Xue-qin Liu ◽  
Xiao-jie Niu ◽  
Xiao-qiang Wang ◽  
Rong Jiang ◽  
...  
Keyword(s):  
Neurodegenerative Diseases ◽  
Adult Neurogenesis ◽  
Neural Progenitor Cells ◽  
Normal Function ◽  
Mammalian Brain ◽  
Middle Aged ◽  
Adult Mice ◽  
Age Related ◽  
Sirna Interference ◽  
Shed Light

Abstract Adult neurogenesis is the ongoing generation of functional new neurons from neural progenitor cells (NPCs) in the mammalian brain. However, this process declines with aging, which is implicated in the recession of brain function and neurodegeneration. Understanding the mechanism of adult neurogenesis and stimulating it will benefit the mitigation of neurodegenerative diseases. Autophagy, a highly conserved process of cellular degradation, is essential for maintaining cellular homeostasis and normal function. Whether and how autophagy affects adult neurogenesis remains poorly understood. In present study, we revealed a close connection between impaired autophagy and adult neurogenetic decline. Expression of autophagy-related genes and autophagic activity were significantly declined in the middle-aged subventricular/subgranular zone (SVZ/SGZ) homogenates and cultured NPCs, and inhibiting autophagy by siRNA interference resulted in impaired pluripotency of NPCs. Conversely, stimulating autophagy by rapamycin not only revitalized the viability and pluripotency of middle-aged NPCs, but also facilitated the neurogenesis in middle-aged SVZ/SGZ. More importantly, autophagic activation by rapamycin also ameliorated the olfactory sensitivity and cognitional capacities in middle-aged mice. Taken together, our results reveal that compromised autophagy is involved in the decline of adult neurogenesis, which could be reversed by autophagy activation. It also shed light on the regulation of adult neurogenesis and paves the way for developing therapeutic strategy for aging and neurodegenerative diseases.

Role of melatonin in regulating neurogenesis: Implications for the neurodegenerative pathology and analogous therapeutics for Alzheimer’s disease

2020 ◽  
Vol 3 (2) ◽  
pp. 216-242 ◽  
Author(s):  
Mayuri Shukla ◽  
Areechun Sotthibundhu ◽  
Piyarat Govitrapong
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Adult Neurogenesis ◽  
Adult Brain ◽  
Therapeutic Approaches ◽  
Therapeutic Implications ◽  
Cell Proliferation And Differentiation ◽  
Proliferation And Differentiation ◽  
Progenitor Cell Proliferation

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.   

scholarly journals An architectonic type principle in the development of laminar patterns of cortico-cortical connections

2021 ◽  
Author(s):  
Sarah F. Beul ◽  
Alexandros Goulas ◽  
Claus C. Hilgetag
Keyword(s):  
Structural Connectivity ◽  
Macaque Monkey ◽  
Brain Regions ◽  
Adult Brain ◽  
Mammalian Brain ◽  
Cortical Connections ◽  
Cortical Projections ◽  
Structural Connections ◽  
High Degree ◽  
The Brain

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.

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