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Interneuron AND Neurogenesis

Christin Weissleder, Hayley F North, Cynthia Shannon Weickert
PURPOSE OF REVIEW: Aberrant neurogenesis may contribute to the pathogenesis, pathophysiology and symptoms of schizophrenia. This review summarizes the state of knowledge of adult neurogenesis in schizophrenia and raises important unanswered questions. We highlight how alterations in signalling molecules in the local and peripheral environments in schizophrenia may regulate adult neurogenesis in the human subgranular zone of the hippocampus and the subependymal zone (SEZ). RECENT FINDINGS: Cell proliferation and density of mature neurons are reduced in the hippocampus, yet the extent of adult neurogenesis remains unexplored in the SEZ in schizophrenia...
February 12, 2019: Current Opinion in Psychiatry
Shuang Peng, Bo Yang, Meng Yun Duan, Zi Wei Liu, Wei Feng Wang, Xiang Zhi Zhang, Bo Xu Ren, Feng Ru Tang
The effect of acute X-ray irradiation with 2 Gy or fractionated exposure with 0.2 Gy continuously for 10 days (0.2 Gy × 10 = 2 Gy) was evaluated in the postnatal day 21 (P21) BALB/c mouse model. Both acute and fractionated irradiation induced impairment of cell proliferation and neurogenesis in the subgranular zone of the dentate gyrus labeled by Ki67 and doublecortin, respectively. Parvalbumin immunopositive interneurons in the subgranular zone were also reduced significantly. However, the 2 patterns of irradiation did not affect animal weight gain when measured at ages of P90 and P180 or 69 and 159 days after irradiation...
January 2019: Dose-response: a Publication of International Hormesis Society
Giovanna Paolone, Chiara Falcicchia, Francesca Lovisari, Merab Kokaia, William J Bell, Tracie Fradet, Mario Barbieri, Lars U Wahlberg, Dwaine F Emerich, Michele Simonato
Neurotrophic factors are candidates for treating epilepsy but their development has been hampered by difficulties in achieving stable and targeted delivery of efficacious concentrations within the desired brain region. We have developed an encapsulated cell technology that overcomes these obstacles by providing a targeted, continuous, de novo synthesized source of high levels of neurotrophic molecules from human clonal ARPE-19 cells encapsulated into hollow fiber membranes. Here we illustrate the potential of this approach for delivering glial cell line-derived neurotrophic factor (GDNF) directly to the hippocampus of epileptic rats...
January 21, 2019: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Concepció Marin, Cristobal Langdon, Isam Alobid, Mireya Fuentes, Mercè Bonastre, Joaquim Mullol
Excitotoxicity consists in a cascade of intracellular events initiated by an excessive release of glutamate and hyperactivation of glutamatergic receptors that is involved in several pathologies, including traumatic brain injury and neurodegenerative diseases such as Parkinson's disease. Both disorders are a common cause of olfactory dysfunction. We previously reported a role for glutamate excitotoxicity in olfactory dysfunction showing an olfactory deficit 1 week after lesion and a spontaneous recovery 2 weeks after excitotoxicity lesion of the olfactory bulbs (OBs)...
January 19, 2019: Molecular Neurobiology
Alexandra Angelova, Jean-Claude Platel, Christophe Béclin, Harold Cremer, Nathalie Coré
During postnatal OB neurogenesis, predetermined stem cells residing in the ventricular-subventricular zone continuously generate progenitors that migrate in the rostral migratory stream and integrate into the OB. Although the vast majority of these postnatally generated interneurons are inhibitory, a sub-fraction represents glutamatergic neurons that integrate into the superficial glomerular layer. In the present work we demonstrate that the bHLH transcription factor NeuroD6 is specifically and transitorily expressed in the dorsal neurogenic lineage that generates glutamatergic JGCs for the OB...
December 27, 2018: Journal of Comparative Neurology
Dinesh Upadhya, Bharathi Hattiangady, Olagide W Castro, Bing Shuai, Maheedhar Kodali, Sahithi Attaluri, Adrian Bates, Yi Dong, Su-Chun Zhang, Darwin J Prockop, Ashok K Shetty
Medial ganglionic eminence (MGE)-like interneuron precursors derived from human induced pluripotent stem cells (hiPSCs) are ideal for developing patient-specific cell therapy in temporal lobe epilepsy (TLE). However, their efficacy for alleviating spontaneous recurrent seizures (SRS) or cognitive, memory, and mood impairments has never been tested in models of TLE. Through comprehensive video- electroencephalographic recordings and a battery of behavioral tests in a rat model, we demonstrate that grafting of hiPSC-derived MGE-like interneuron precursors into the hippocampus after status epilepticus (SE) greatly restrained SRS and alleviated cognitive, memory, and mood dysfunction in the chronic phase of TLE...
January 2, 2019: Proceedings of the National Academy of Sciences of the United States of America
Nichola Marie Brydges, Anna Moon, Lowenna Rule, Holly Watkin, Kerrie L Thomas, Jeremy Hall
Experience of traumatic events in childhood is linked to an elevated risk of developing psychiatric disorders in adulthood. The neurobiological mechanisms underlying this phenomenon are not fully understood. The limbic system, particularly the hippocampus, is significantly impacted by childhood trauma. In particular, it has been hypothesised that childhood stress may impact adult hippocampal neurogenesis (AHN) and related behaviours, conferring increased risk for later mental illness. Stress in utero can lead to impaired hippocampal synaptic plasticity, and stress in the first 2-3 weeks of life reduces AHN in animal models...
December 10, 2018: Translational Psychiatry
Ricardo J Rodrigues, Joana M Marques, Rodrigo A Cunha
ATP and adenosine are released from cells as a function of their metabolic activity, being important cell-to-cell communication signals. Both purines are also released from neurons in an activity-dependent manner, with several established roles to fine tune brain function in adults, as best heralded by the effects of caffeine, an antagonist of adenosine receptors. Purines are also dynamically released from early neurogenesis and different purine receptors are dynamically expressed throughout development. Accordingly, emerging evidence supports multiple roles for purinergic signalling in the control of different processes of brain development, such as embryonic neurogenesis, migration of principal neurons and interneurons, guidance for neuronal connectivity, synaptogenesis and synaptic stability/elimination...
December 4, 2018: Seminars in Cell & Developmental Biology
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
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