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 Spatiotemporal expression and transcriptional perturbations by long noncoding RNAs in the mouse brain

2015 ◽  
Vol 112 (22) ◽  
pp. 6855-6862 ◽  
Author(s):  
Loyal A. Goff ◽  
Abigail F. Groff ◽  
Martin Sauvageau ◽  
Zachary Trayes-Gibson ◽  
Diana B. Sanchez-Gomez ◽  
...  
Keyword(s):  
Neural Development ◽  
Expression Patterns ◽  
Noncoding Rnas ◽  
Brain Regions ◽  
Long Noncoding Rnas ◽  
Adult Brain ◽  
Mammalian Brain ◽  
Endogenous Expression ◽  
Spatiotemporal Expression

Long noncoding RNAs (lncRNAs) have been implicated in numerous cellular processes including brain development. However, the in vivo expression dynamics and molecular pathways regulated by these loci are not well understood. Here, we leveraged a cohort of 13 lncRNA-null mutant mouse models to investigate the spatiotemporal expression of lncRNAs in the developing and adult brain and the transcriptome alterations resulting from the loss of these lncRNA loci. We show that several lncRNAs are differentially expressed both in time and space, with some presenting highly restricted expression in only selected brain regions. We further demonstrate altered regulation of genes for a large variety of cellular pathways and processes upon deletion of the lncRNA loci. Finally, we found that 4 of the 13 lncRNAs significantly affect the expression of several neighboring protein-coding genes in a cis-like manner. By providing insight into the endogenous expression patterns and the transcriptional perturbations caused by deletion of the lncRNA locus in the developing and postnatal mammalian brain, these data provide a resource to facilitate future examination of the specific functional relevance of these genes in neural development, brain function, and disease.

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 The Microtubule Severing Protein Katanin Regulates Proliferation of Neuronal Progenitors in Embryonic and Adult Neurogenesis

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Franco L. Lombino ◽  
Mary Muhia ◽  
Jeffrey Lopez-Rojas ◽  
Monika S. Brill ◽  
Edda Thies ◽  
...  
Keyword(s):  
Adult Neurogenesis ◽  
Critical Role ◽  
Mammalian Brain ◽  
Cellular Functions ◽  
Microtubule Severing ◽  
Neuronal Progenitor ◽  
Neuronal Progenitors ◽  
Adult Hippocampus

Abstract Microtubule severing regulates cytoskeletal rearrangement underlying various cellular functions. Katanin, a heterodimer, consisting of catalytic (p60) and regulatory (p80) subunits severs dynamic microtubules to modulate several stages of cell division. The role of p60 katanin in the mammalian brain with respect to embryonic and adult neurogenesis is poorly understood. Here, we generated a Katna1 knockout mouse and found that consistent with a critical role of katanin in mitosis, constitutive homozygous Katna1 depletion is lethal. Katanin p60 haploinsufficiency induced an accumulation of neuronal progenitors in the subventricular zone during corticogenesis, and impaired their proliferation in the adult hippocampus dentate gyrus (DG) subgranular zone. This did not compromise DG plasticity or spatial and contextual learning and memory tasks employed in our study, consistent with the interpretation that adult neurogenesis may be associated with selective forms of hippocampal-dependent cognitive processes. Our data identify a critical role for the microtubule-severing protein katanin p60 in regulating neuronal progenitor proliferation in vivo during embryonic development and adult neurogenesis.

scholarly journals The cell cycle–apoptosis connection revisited in the adult brain

2005 ◽  
Vol 171 (4) ◽  
pp. 641-650 ◽  
Author(s):  
Sylvian Bauer ◽  
Paul H. Patterson
Keyword(s):  
Cell Cycle ◽  
Dna Repair ◽  
Dna Synthesis ◽  
Adult Neurogenesis ◽  
Adult Brain ◽  
Brdu Incorporation ◽  
High Dose ◽  
Brdu Labeling ◽  
Postmitotic Neurons

Adult neurogenesis is studied in vivo using thymidine analogues such as bromodeoxyuridine (BrdU) to label DNA synthesis during the S phase of the cell cycle. However, BrdU may also label DNA synthesis events not directly related to cell proliferation, such as DNA repair and/or abortive reentry into the cell cycle, which can occur as part of an apoptotic process in postmitotic neurons. In this study, we used three well-characterized models of injury-induced neuronal apoptosis and the combined visualization of cell birth (BrdU labeling) and death (Tdt-mediated dUTP-biotin nick end labeling) to investigate the specificity of BrdU incorporation in the adult mouse brain in vivo. We present evidence that BrdU is not significantly incorporated during DNA repair and that labeling is not detected in vulnerable or dying postmitotic neurons, even when a high dose of BrdU is directly infused into the brain. These findings have important implications for a controversy surrounding adult neurogenesis: the connection between cell cycle reactivation and apoptosis of terminally differentiated neurons.

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 Overexpression of cdk4 and cyclinD1 triggers greater expansion of neural stem cells in the adult mouse brain

2011 ◽  
Vol 208 (5) ◽  
pp. 937-948 ◽  
Author(s):  
Benedetta Artegiani ◽  
Dirk Lindemann ◽  
Federico Calegari
Keyword(s):  
Stem Cells ◽  
Neural Stem Cells ◽  
Adult Neurogenesis ◽  
Adult Mouse ◽  
Physiological Role ◽  
Mammalian Brain ◽  
Temporal Control ◽  
Somatic Stem Cells

Neural stem cells (NSCs) in the adult mammalian brain generate neurons and glia throughout life. However, the physiological role of adult neurogenesis and the use of NSCs for therapy are highly controversial. One factor hampering the study and manipulation of neurogenesis is that NSCs, like most adult somatic stem cells, are difficult to expand and their switch to differentiation is hard to control. In this study, we show that acute overexpression of the cdk4 (cyclin-dependent kinase 4)–cyclinD1 complex in the adult mouse hippocampus cell-autonomously increases the expansion of neural stem and progenitor cells while inhibiting neurogenesis. Importantly, we developed a system that allows the temporal control of cdk4–cyclinD1 overexpression, which can be used to increase the number of neurons generated from the pool of manipulated precursor cells. Beside providing a proof of principle that expansion versus differentiation of somatic stem cells can be controlled in vivo, our study describes, to the best of our knowledge, the first acute and inducible temporal control of neurogenesis in the mammalian brain, which may be critical for identifying the role of adult neurogenesis, using NSCs for therapy, and, perhaps, extending our findings to other adult somatic stem cells.

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.

Effects and Potential Mechanisms of Alcohol Use Disorder on the Fate Determination of Newly Born Neurons in the Hippocampus

2020 ◽  
Vol 55 (6) ◽  
pp. 598-602
Author(s):  
Zahra Shabani ◽  
Mohsen Jafarzadeh Gharehziaaddin
Keyword(s):  
Hippocampal Neurogenesis ◽  
Adult Brain ◽  
Adult Hippocampal Neurogenesis ◽  
Mammalian Brain ◽  
Extrinsic Factors ◽  
Proliferation And Differentiation ◽  
Underlying Mechanisms

Abstract In the adult mammalian brain, new functional neurons are generated throughout life because of sustained proliferation and differentiation of neural stem cells (NSCs). The subventricular zone (SVZ), lining the lateral ventricle, and the subgranular zone (SGZ) in the dentate gyrus (DG) of the hippocampus are the two major neurogenic regions in the adult brain. This process is not fixed but is highly modulated by numerous intrinsic and extrinsic factors. Neurogenesis has become in the focus of interest for its involvement in repairing the damaged brain and this motivates researchers to detect controlling mechanisms of this process. Recent evidence suggests that alcohol usage can directly influence adult hippocampal neurogenesis, but its mechanisms remain a matter for debate. Thus, this review summarizes in vivo/in vitro studies on the role of alcohol in hippocampal neurogenesis during adulthood and clarifies its underlying mechanisms by highlighting neurotransmitters and their receptors.

scholarly journals Migraine Disability, Quality of Life, and Its Predictors

2020 ◽  
Vol 27 (1) ◽  
pp. 18-23
Author(s):  
Pradeep R. ◽  
Nemichandra S. C. ◽  
Harsha S. ◽  
Radhika K.
Keyword(s):  
Quality Of Life ◽  
Primary Headache ◽  
Well Being ◽  
Anxiety And Depression ◽  
Middle Aged ◽  
Severity Of Disability ◽  
Significant Disability ◽  
Psychiatric Conditions ◽  
Headache Impact

Background: Migraine is the most disabling primary headache and is the second most prevalent primary headache affecting middle-aged females more. However, diagnosis and treatment of migraine persists to be inadequate. Despite being a major cause of disability, works done to understand the burden and impact of migraine on daily living remains sparse. Migraine negatively affects one’s sense of well-being in life, and understanding these factors will enable us to better manage the disease. Objective: To estimate the severity of disability and impairment in quality of life (QOL) secondary to migraine. To enumerate and analyze the factors predicting severity of disability and impairment in QOL secondary to migraine. Materials and Methods: In this descriptive study, 108 consecutive migraineurs were studied. Headache impact, migraine disability, migraine-specific quality of life (MSQoL), and psychiatric comorbidities were studied using validated questionnaires. Results: Migraine was seen in 89 females and 19 males with most being in the age group of 20–40 years. Headaches had considerable to relentless impact on the sufferers. Majority of them had a highly significant disability and negatively impacted “MSQoL,”, being affected in all the domains. There was also coexisting anxiety and depression with migraine. Conclusion: Migraine was more frequently seen in young- and middle-aged females. The longer duration, more frequent migraine attacks, and headache with substantial to severe impact were predictors of both disability and detrimental effects on QOL in migraineurs. Comorbid psychiatric conditions were found to be a significant contributary factor.

scholarly journals Quality of Life and Clinical Correlates in Adults with Social Phobia: A Scoping Review

2021 ◽  
Vol 17 (1) ◽  
pp. 224-234
Author(s):  
Hui Miin Lau ◽  
Kai Samuel Sim ◽  
Qian Hui Chew ◽  
Kang Sim
Keyword(s):  
Quality Of Life ◽  
Social Phobia ◽  
Scoping Review ◽  
Negative Impact ◽  
Well Being ◽  
Clinical Correlates ◽  
Psychiatric Conditions ◽  
Clinical Profiles ◽  
Suicidal Ideas

Objective: In light of the substantial clinical and societal burden of social phobia (SP) and impact on the sense of well-being of affected individuals, we sought to summarise extant data related to quality of life and relevant correlates in adults with SP to distill clinical profiles for earlier identification and appropriate management. Methods: A scoping review was carried out on studies examining quality of life in adults with SP and clinical correlates within different settings. PubMed/Medline and Web of Science databases were searched for relevant articles beginning from database inception until May 2021. Results: A total of 25 papers were included. Most of the studies (92%) were cross sectional in nature (80%), conducted in the West (92%), and within clinic or community settings (88%). Patients with comorbid psychiatric conditions, and undergraduate students reported higher rates of SP compared with community population. Significant correlates of SP included demographic (such as females, younger age, living alone, fewer years of education, unemployment) and clinical factors (such as family history of anxiety disorders, suicidal ideas, avoidant personality features). SP was widely associated with decreased QoL involving several domains and especially related to complexity, greater number of feared or trigger situations, and comorbid medical and psychiatric conditions. Conclusion: SP is not uncommon within clinical, and undergraduate populations, and has a significantly negative impact on quality of life. Awareness of its associated clinical profiles allows better identification and overall management of this condition including improvement in QoL.

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