Regulation and Function of Adult Neurogenesis: From Genes to Cognition

Aimone, James B.; Li, Yan; Lee, Star W.; Clemenson, Gregory D.; Deng, Wei; Gage, Fred H.

doi:10.1152/physrev.00004.2014

Cited by 527 publications

(567 citation statements)

References 362 publications

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“…1). The activated neutrophils release an assortment of proteins, such as MPO, The Journal of Immunologylactoferrin, serine protease, collagenase, and gelatinase, which contribute to ALI (24). Based on the literature, we sought to detect the presence of MPO in BALF, and our data showed much higher levels of MPO in BALF than those in sham control mice (Fig.…”

Section: Accumulated Neutrophils In Balf From Intestinal Ir-induced Amentioning

confidence: 91%

Endoplasmic Reticulum Stress of Neutrophils Is Required for Ischemia/Reperfusion–Induced Acute Lung Injury

Chen

Jia

et al. 2015

The Journal of Immunology

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Diverse clinical factors, including intestinal ischemia, contribute to acute lung injury (ALI), which has up to a 40% mortality rate. During the development of lung injury an immune response is elicited that exacerbates the lung insult. Neutrophils have been well studied in mediating the pulmonary insults through an assortment of mechanisms, such as release of granule contents and production of proinflammatory cytokines due to the overactivation of complement and cytokines. In this study, we found that enhanced endoplasmic reticulum (ER) stress was observed in infiltrated neutrophils in the early stage of an ALI mice model. In neutrophils, complement 5a (C5a) inspires strong ER stress through inositol-requiring kinase 1a and, to a less extent, the protein kinase R–like ER kinase signaling pathway. The granule release induced by C5a was ER stress mediated. Knowkdown of X-box–binding protein 1, a downstream signaling molecule of inositol-requiring kinase 1a, impaired granule release, based on myeloperoxidase production. Further analysis revealed that C5a induced ER stress by binding to C5a receptor in neutrophils. Using xbpf/f MRP8-cre mice in which X-box–binding protein 1 is deficient specifically in neutrophils and ER stress is deprived, we confirmed that ER stress in neutrophils was required for granule release in vivo and led to ALI, whereas dampening ER stress in neutrophils substantially alleviated ALI. Taken together, our results demonstrated that C5a receptor–mediated ER stress induced granule release in neutrophils, contributing to the development of ALI. This novel mechanism suggests a new potential therapeutic target in autophagy regulation for ALI.

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Section: Accumulated Neutrophils In Balf From Intestinal Ir-induced Amentioning

confidence: 91%

Endoplasmic Reticulum Stress of Neutrophils Is Required for Ischemia/Reperfusion–Induced Acute Lung Injury

Chen

Jia

et al. 2015

The Journal of Immunology

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“…Dorsal hippocampus is thought to contribute to spatial memory formation and the associative encoding of discrete stimuli. Behavioral analyses using different approaches for ablation of adult hippocampal neurogenesis have suggested a connection between neurogenesis and cognitive functions, such as spatial and temporal encoding and contextual discrimination (Aimone et al 2014). Ventral hippocampus has been associated with modulation of affective behaviors and emotionally salient memories (Kheirbek and Hen 2011;Kheirbek et al 2013;Tannenholz et al 2014;Wu and Hen 2014).…”

Section: Role Of Adult Hippocampal Neurogenesis In Cognitive and Affementioning

confidence: 99%

Adult Neurogenesis and Psychiatric Disorders

Kang

Wen

Song

et al. 2016

Cold Spring Harb Perspect Biol

160

118

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Psychiatric disorders continue to be among the most challenging disorders to diagnose and treat because there is no single genetic or anatomical locus that is causative for the disease. Current treatments are often blunt tools used to ameliorate the most severe symptoms, at the risk of disrupting functional neural systems. There is a critical need to develop new therapeutic strategies that can target circumscribed functional or anatomical domains of pathology. Adult hippocampal neurogenesis may be one such domain. Here, we review the evidence suggesting that adult hippocampal neurogenesis plays a role in emotional regulation and forms of learning and memory that include temporal and spatial memory encoding and context discrimination, and that its dysregulation is associated with psychiatric disorders, such as affective disorders, schizophrenia, and drug addiction. Further, adult neurogenesis has proven to be an effective model to investigate basic processes of neuronal development and converging evidence suggests that aberrant neural development may be an etiological factor, even in late-onset diseases. Constitutive neurogenesis in the hippocampus of the mature brain reflects large-scale plasticity unique to this region and could be a potential hub for modulation of a subset of cognitive and affective behaviors that are affected by multiple psychiatric disorders.

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“…Microglia are distributed in the hilus and granular cell layer in the adult DG (18). Microglia constitute an important component of the neurogenic niche.…”

Section: Factors That Affect Adult Hippocampal Neurogenesismentioning

confidence: 99%

“…During neurogenesis, microglia both remove apoptotic cells, and potentially influence proliferation, differentiation and neural survival with their secretagogues. Microglia are thought to contribute to the neurogenic niche mostly through neurotrophic factor [BDNF, insulin-like growth factor (IGF-1)], and cytokine and chemokine secretions (18). BDNF is the most important neurotrophic factor that stimulates neural stem cell proliferation and neural survival, and also a key element of memory formation.…”

Section: Factors That Affect Adult Hippocampal Neurogenesismentioning

confidence: 99%

The Role of Adult Hippocampal Neurogenesis in Learning and Memory Function

Kaptan¹,

Üzüm²

2016

tnd

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Adult hippocampal neurogenesis is the lifelong production of new functional neurons from neural stem cells in the adult brain. Production of neurons in the adult brain is limited to two areas. One of these is the subgranular region in the hippocampus dentate gyrus (DG), the other is the subventricular zone of the lateral ventricles. New neurons produced in the hippocampus DG functionally integrate into mature circuits, and contribute to cognition and emotional control, learning and memory functions in particular. It is still unclear how that contribution occurs and a key issue that is being intensively investigated. Hippocampal neurogenesis declines both with age and in neurodegenerative diseases characterized by deterioration of memory. Understanding the contribution of hippocampal neurogenesis to memory function and investigating factors that affect neurogenesis have gained importance for protective or therapeutic approaches against these neurodegenerative diseases. It is suggested that new neurons produced in the DG contribute to spatial and episodic memory function by pattern separation (prevent overlapping of similar information by making separate presentations) through their electrophysiologic properties (being stimulated easier than mature neurons) in the maturation process. Hippocampal neurogenesis is important in episodic and spatial memory formation. In this review we will try to explain how hippocampal neurogenesis occurs, factors that affect the neurogenesis process, and the role of neurogenesis in memory function based on the present literature.Keywords: Adult hippocampal neurogenesis, dentate gyrus, learning and memory, pattern separation Erişkin hipokampal nörogenez, erişkin beyninde yaşam boyu nöral kök hücrelerden yeni fonksiyonel nöron üretimidir. Erişkin beyninde nöron üretimi iki bölgeye sınırlıdır. Bunlardan biri hipokampus dentat girusundaki (DG) subgranüler bölge, diğeri lateral ventriküllerin subventriküler bölgesidir. Hipokampus DG'sinde üretilen yeni nöronlar fonksiyonel olarak olgun devrelere entegre olurlar, özellikle öğrenme ve hafıza fonksiyonu olmak üzere kognisyon ve emosyonel kontrole katkıda bulunurlar. Bu katkının nasıl gerçekleştiği hala açık değildir ve yoğun olarak araştırılan önemli bir konudur. Hipokampal nörogenezin hem yaşla birlikte hem yaşa bağlı hafızanın bozulması ile karakterize nörodejeneratif hastalıklarda azaldığı bilinmektedir. Hipokampal nörogenezin hafıza fonksiyonuna katkısını anlamak ve nörogenezi etkileyen faktörleri araştırmak bu nörodejeneratif hastalıklara karşı koruyucu ya da tedavi edici yaklaşımlar için önem kazanmıştır. Hipokampal DG'de üretilen yeni nöronların olgunlaşma süreçlerindeki elektrofizyolojik özellikleri (olgun nöronlara göre daha kolay uyarılabilir olmaları) sayesinde patern ayrımı (hipokampusa gelen benzer bilgilerin ayrı sunumları yapılarak örtüşmelerinin engellenmesi) yaparak spasyal ve epizodik hafıza fonksiyonuna katkıda bulundukları düşünülmektedir. Bu derlemede hipokampal nörogenezin nasıl oluştuğunu, nörogenez sürecine etkili fak...

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Regulation and Function of Adult Neurogenesis: From Genes to Cognition

Cited by 527 publications

References 362 publications

Endoplasmic Reticulum Stress of Neutrophils Is Required for Ischemia/Reperfusion–Induced Acute Lung Injury

Endoplasmic Reticulum Stress of Neutrophils Is Required for Ischemia/Reperfusion–Induced Acute Lung Injury

Adult Neurogenesis and Psychiatric Disorders

The Role of Adult Hippocampal Neurogenesis in Learning and Memory Function

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