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Interneuron AND Neurogenesis

Burak Tepe, Matthew C Hill, Brandon T Pekarek, Patrick J Hunt, Thomas J Martin, James F Martin, Benjamin R Arenkiel
Cellular heterogeneity within the mammalian brain poses a challenge toward understanding its complex functions. Within the olfactory bulb, odor information is processed by subtypes of inhibitory interneurons whose heterogeneity and functionality are influenced by ongoing adult neurogenesis. To investigate this cellular heterogeneity and better understand adult-born neuron development, we utilized single-cell RNA sequencing and computational modeling to reveal diverse and transcriptionally distinct neuronal and nonneuronal cell types...
December 4, 2018: Cell Reports
Leiah M Luoma, Fred B Berry
BACKGROUND: NPAS3 encodes a transcription factor which has been associated with multiple human psychiatric and neurodevelopmental disorders. In mice, deletion of Npas3 was found to cause alterations in neurodevelopment, as well as a marked reduction in neurogenesis in the adult mouse hippocampus. This neurogenic deficit, alongside the reduction in cortical interneuron number, likely contributes to the behavioral and cognitive alterations observed in Npas3 knockout mice. Although loss of Npas3 has been found to affect proliferation and apoptosis, the molecular function of NPAS3 is largely uncharacterized outside of predictions based on its high homology to bHLH-PAS transcription factors...
December 3, 2018: BMC Molecular Biology
Ramin M Farahani, Saba Rezaei-Lotfi, Mary Simonian, Munira Xaymardan, Neil Hunter
Consistent adult neurogenic activity in humans is observed in specific niches within the central nervous system. However, the notion of an adult neurogenic niche is challenged by accumulating evidence for ectopic neurogenic activity in other cerebral locations. Herein we interface precision of ultrastructural resolution and anatomical simplicity of accessible human dental pulp neurogenic zone to address this conflict. We disclose a basal level of adult neurogenic activity characterized by glial invasion of terminal microvasculature followed by release of individual platelet-derived growth factor receptor-β mural pericytes and subsequent reprogramming into NeuN+ local interneurons...
November 23, 2018: Journal of Comparative Neurology
Young J Kim, Sattar Khoshkhoo, Jan C Frankowski, Bingyao Zhu, Saad Abbasi, Sunyoung Lee, Ye Emily Wu, Robert F Hunt
Considerable evidence suggests loss-of-function mutations in the chromatin remodeler CHD2 contribute to a broad spectrum of human neurodevelopmental disorders. However, it is unknown how CHD2 mutations lead to impaired brain function. Here we report mice with heterozygous mutations in Chd2 exhibit deficits in neuron proliferation and a shift in neuronal excitability that included divergent changes in excitatory and inhibitory synaptic function. Further in vivo experiments show that Chd2+/- mice displayed aberrant cortical rhythmogenesis and severe deficits in long-term memory, consistent with phenotypes observed in humans...
October 13, 2018: Neuron
Heng Zhang, Xiao He, Yufei Mei, Qingzhou Ling
Parvalbumin (PV) positive interneurons in the subgranular zone (SGZ) can regulate adult hippocampal neurogenesis. ErbB4 is mainly expressed in PV neurons in the hippocampus and is crucial for keeping normal function of PV neurons. However, whether ErbB4 in PV interneurons affects the adult hippocampal neurogenesis remains unknown. In the present study, we deleted ErbB4 specifically in PV neurons by crossing PV-Cre mice with ErbB4f/f mice. Results of BrdU labeling and NeuN staining revealed that the proliferation of neural progenitors was increased but the survival and maturation of newborn neurons were decreased in the hippocampus of mice after deleting ErbB4 in PV neurons, suggesting that ErbB4 in PV neurons is closely associated with the process of adult hippocampal neurogenesis...
October 15, 2018: Journal of Comparative Neurology
Fiorenza Stagni, Andrea Giacomini, Marco Emili, Beatrice Uguagliati, Maria Paola Bonasoni, Renata Bartesaghi, Sandra Guidi
Intellectual disability in Down syndrome (DS) has been attributed to neurogenesis impairment during fetal brain development. Consistently with explicit memory alterations observed in children with DS, fetuses with DS exhibit neurogenesis impairment in the hippocampus, a key region involved in memory formation and consolidation. Recent evidence suggests that the subiculum plays a unique role in memory retrieval, a process that is also altered in DS. While much attention has been devoted to the hippocampus, there is a striking lack of information regarding the subiculum of individuals with DS and DS models...
October 16, 2018: Brain Pathology
Elodie Gaborieau, Anahi Hurtado-Chong, Maria Fernández, Kasum Azim, Olivier Raineteau
Neural stem cells (NSCs) of the postnatal subventricular zone (SVZ) continue producing distinct subtypes of olfactory bulb (OB) interneurons throughout life. Understanding the transcriptional coding of this diversity remains a great challenge of modern neurosciences. Interneurons expressing calretinin (CalR) represent the main interneuron subtype produced in the glomerular cell layer (GL) after birth. Previous studies have suggested that their specification relies on expression of the transcription factor Sp8 by SVZ NSCs...
September 28, 2018: Scientific Reports
Si Wei Wang, Bo Xu Ren, Feng Qian, Xue Zhi Luo, Xi Tang, Xiao Chun Peng, Jiang Rong Huang, Feng Ru Tang
The radioprotective effect of herb epimedium (or yin yang huo) extract (5 g/kg, oral administration daily for 4 weeks) on neurogenesis and cognition after acute radiation exposure with 5.5 Gy was evaluated in Balb/c mice by behavioral tests and immunohistochemical study. The results indicated that epimedium extract could improve animal weight loss, locomotor activity and spatial learning and memory which are similar to pre-irradiation intraperitoneal injection (100 mg/kg) of amifostine phosphate, a well- known radioprotective drug...
August 23, 2018: Neuroscience Research
Andreas Angelidis, Enikő Račeková, Petra Arnoul, Monika Závodská, Adam Raček, Marcela Martončíková
In adult rodents, neuroblasts originating from the subventricular zone migrate tangentially through the rostral migratory stream (RMS) toward the olfactory bulb where they differentiate into interneurons. Neuroblasts in the RMS migrate in chains for a long distance along specifically arranged blood vessels which promote their migration. Although blood vessels in the neurogenic region of the forebrain are present early in development, their rearrangement into this specific pattern takes place during the first postnatal weeks...
November 1, 2018: Brain Research
Hiroo Takahashi, Seiichi Yoshihara, Akio Tsuboi
It has been shown in a variety of mammalian species that sensory experience can regulate the development of various structures, including the retina, cortex, hippocampus, and olfactory bulb (OB). In the mammalian OB, the development of dendrites in excitatory projection neurons, such as mitral and tufted cells, is well known to be dependent on odor experience. Odor experience is also involved in the development of another OB population, a subset of inhibitory interneurons that are generated in the ventricular-subventricular zone throughout life and differentiate into granule cells (GCs) and periglomerular cells...
2018: Frontiers in Molecular Neuroscience
Kevin M Child, Daniel B Herrick, James E Schwob, Eric H Holbrook, Woochan Jang
The olfactory epithelium (OE) of vertebrates is a highly regenerative neuroepithelium, maintained under normal condition by a population of stem and progenitor cells - globose basal cells (GBCs) that also contribute to epithelial reconstitution after injury. However, aging of the OE often leads to neurogenic exhaustion - the disappearance of both GBCs and olfactory sensory neurons (OSNs). Aneuronal tissue may remain as olfactory, with an uninterrupted sheet of apically arrayed microvillar-capped sustentacular cell, or may undergo respiratory metaplasia...
June 22, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Juzoh Umemori, Frederike Winkel, Giuliano Didio, Maria Llach Pou, Eero Castrén
The network hypothesis of depression proposes that mood disorders reflect problems in information processing within particular neural networks. Antidepressants (AD), including selective serotonin reuptake inhibitors (SSRI), function by gradually improving information processing within these networks. AD have been shown to induce a state of juvenile-like plasticity comparable to that observed during developmental critical periods: Such critical-period-like plasticity allows brain networks to better adapt to extrinsic and intrinsic signals...
September 2018: Psychiatry and Clinical Neurosciences
Chiara Falcicchia, Giovanna Paolone, Dwaine F Emerich, Francesca Lovisari, William J Bell, Tracie Fradet, Lars U Wahlberg, Michele Simonato
Brain-derived neurotrophic factor (BDNF) may represent a therapeutic for chronic epilepsy, but evaluating its potential is complicated by difficulties in its delivery to the brain. Here, we describe the effects on epileptic seizures of encapsulated cell biodelivery (ECB) devices filled with genetically modified human cells engineered to release BDNF. These devices, implanted into the hippocampus of pilocarpine-treated rats, highly decreased the frequency of spontaneous seizures by more than 80%. These benefits were associated with improved cognitive performance, as epileptic rats treated with BDNF performed significantly better on a novel object recognition test...
June 15, 2018: Molecular Therapy. Methods & Clinical Development
Dailiany Orechio, Bruna Andrade Aguiar, Giovanne Baroni Diniz, Jackson Cioni Bittencourt, Carlos A S Haemmerle, Ii-Sei Watanabe, Maria Angelica Miglino, Patricia Castelucci
The existence of neurogenesis in the adult brain is a widely recognized phenomenon, occurring in the subventricular zone (SVZ) of the lateral ventricles and the subgranular zone of the dentate gyrus in several vertebrate species. Neural precursors originated in the SVZ migrate to the main olfactory bulb (MOB), originating the rostral migratory stream (RMS) in the process. To better understand the formation of the adult neurogenic niches in dogs, we investigated the cellular composition and morphological organization of these areas in 57 days-old dog fetuses...
May 12, 2018: Anatomical Record: Advances in Integrative Anatomy and Evolutionary Biology
Thorsten R Doeppner, Josephine Herz, Mathias Bähr, Anton B Tonchev, Anastassia Stoykova
The transcription factor (TF) Zbtb20 is important for the hippocampal specification and the regulation of neurogenesis of neocortical projection neurons. Herein, we show a critical involvement of the TF Zbtb20 in the neurogenesis of both projection neurons and interneurons of the olfactory bulb during embryonic stages. Our data indicate that the lack of Zbtb20 significantly diminishes the generation of a set of early-born Tbr2+ neurons during embryogenesis. Furthermore, we provide evidence that Zbtb20 regulates the transition between neurogenesis to gliogenesis in cortical radial glial progenitor cells at the perinatal (E18...
May 11, 2018: Molecular Neurobiology
Caitlin C Winkler, Odessa R Yabut, Santiago P Fregoso, Hector G Gomez, Brett E Dwyer, Samuel J Pleasure, Santos J Franco
Neural progenitor cells in the developing dorsal forebrain give rise to excitatory neurons, astrocytes, and oligodendrocytes for the neocortex. While we are starting to gain a better understanding about the mechanisms that direct the formation of neocortical neurons and astrocytes, far less is known about the molecular mechanisms that instruct dorsal forebrain progenitors to make oligodendrocytes. In this study, we show that Sonic hedgehog (Shh) signaling is required in dorsal progenitors for their late embryonic transition to oligodendrogenesis...
June 6, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Giovanna Ponti, Alice Farinetti, Marilena Marraudino, GianCarlo Panzica, Stefano Gotti
The forebrain ventricular-subventricular zone (V-SVZ) continuously generates new neurons throughout life. Neural stem cells (type B1 cells) along the lateral ventricle become activated, self-renew, and give rise to proliferating precursors which progress along the neurogenic lineage from intermediate progenitors (type C cells) to neuroblasts (type A cells). Neuroblasts proliferate and migrate into the olfactory bulb and differentiate into different interneuronal types. Multiple factors regulate each step of this process...
2018: Frontiers in Endocrinology
Suijuan Zhong, Shu Zhang, Xiaoying Fan, Qian Wu, Liying Yan, Ji Dong, Haofeng Zhang, Long Li, Le Sun, Na Pan, Xiaohui Xu, Fuchou Tang, Jun Zhang, Jie Qiao, Xiaoqun Wang
The mammalian prefrontal cortex comprises a set of highly specialized brain areas containing billions of cells and serves as the centre of the highest-order cognitive functions, such as memory, cognitive ability, decision-making and social behaviour. Although neural circuits are formed in the late stages of human embryonic development and even after birth, diverse classes of functional cells are generated and migrate to the appropriate locations earlier in development. Dysfunction of the prefrontal cortex contributes to cognitive deficits and the majority of neurodevelopmental disorders; there is therefore a need for detailed knowledge of the development of the prefrontal cortex...
March 22, 2018: Nature
Naoki Sawada, Takenori Kotani, Tasuku Konno, Jajar Setiawan, Yuka Nishigaito, Yasuyuki Saito, Yoji Murata, Ken-Ichi Nibu, Takashi Matozaki
In the mouse olfactory bulb (OB), interneurons such as granule cells and periglomerular cells are continuously replaced by adult-born neurons, which are generated in the subventricular zone (SVZ) of the brain. We have now investigated the role of commensal bacteria in regulation of such neuronal cell turnover in the adult mouse brain. Administration of mixture of antibiotics to specific pathogen-free (SPF) mice markedly attenuated the incorporation of bromodeoxyuridine (BrdU) into the SVZ cells. The treatment with antibiotics also reduced newly generated BrdU-positive neurons in the mouse OB...
April 15, 2018: Biochemical and Biophysical Research Communications
Alexandra Angelova, Marie-Catherine Tiveron, Harold Cremer, Christophe Beclin
In the perinatal and adult forebrain, regionalized neural stem cells lining the ventricular walls produce different types of olfactory bulb interneurons. Although these postnatal stem cells are lineage related to their embryonic counterparts that produce, for example, cortical, septal, and striatal neurons, their output at the level of neuronal phenotype changes dramatically. Tiveron et al. investigated the molecular determinants underlying stem cell regionalization and the gene expression changes inducing the shift from embryonic to adult neuron production...
2018: Journal of Experimental Neuroscience
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