Negative regulation of neurogenesis and spatial memory by NR2B‐containing NMDA receptors

Mei, Hu; Sun, Yongjun; Zhou, Qi‐Gang; Chen, Ling; Hu, Yao; Luo, Chunxia; Wu, Jiayi; Jin, Xu; Li, Lixin; Zhu, Dong‐Ya

doi:10.1111/j.1471-4159.2008.05554.x

Cited by 61 publications

(48 citation statements)

References 75 publications

(183 reference statements)

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“…Lowering corticosterone secretion from midlife (Montaron et al 2006) or a midlife vitamin A supplementation (Touyarot et al 2013) for the rest of the animal's life prevents age-related spatial memory deficits and age-related decline in neurogenesis. In a young subject, pharmacological approaches, consisting of peripheral treatment with the cognitive enhancer ginseng (Qiao et al 2005), the peptidergic drug P21 (Li et al 2010), the histone acetyltransferases CBP/p300 (Chatterjee et al 2013), hippocampal gene transfer of VEGF (Cao et al 2004), blockade of NR2B-containing NMDAR (Hu et al 2008), stimulation of entorhinal cortex (Stone et al 2011a), or deletion of Toll-like receptors (TLRs) (Okun et al 2010), all promoted adult neurogenesis and facilitated memory performances in different learning tasks (contextual fear-conditioning paradigm, associative passive avoidance, and water maze).…”

Section: Correlationsmentioning

confidence: 99%

Interaction between Neurogenesis and Hippocampal Memory System: New Vistas

Abrous

Wojtowicz

2015

Cold Spring Harb Perspect Biol

102

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During the last decade, the questions on the functionality of adult neurogenesis have changed their emphasis from if to how the adult-born neurons participate in a variety of memory processes. The emerging answers are complex because we are overwhelmed by a variety of behavioral tasks that apparently require new neurons to be performed optimally. With few exceptions, the hippocampal memory system seems to use the newly generated neurons for multiple roles. Adult neurogenesis has given the dentate gyrus new capabilities not previously thought possible within the scope of traditional synaptic plasticity. Looking at these new developments from the perspective of past discoveries, the science of adult neurogenesis has emerged from its initial phase of being, first, a surprising oddity and, later, exciting possibility, to the present state of being an integral part of mainstream neuroscience. The answers to many remaining questions regarding adult neurogenesis will come along only with our growing understanding of the functionality of the brain as a whole. This, in turn, will require integration of multiple levels of organization from molecules and cells to circuits and systems, ultimately resulting in comprehension of behavioral outcomes.

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Section: Correlationsmentioning

confidence: 99%

Interaction between Neurogenesis and Hippocampal Memory System: New Vistas

Abrous

Wojtowicz

2015

Cold Spring Harb Perspect Biol

102

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“…Indeed, in the SGZ, NSC proliferation was found to be inhibited by NMDAR activation in a feedback manner (Cameron et al, 1995), through either the activation of dentate gyrus granule cells or direct NMDAR signaling in the NSCs. Evidence based on cultured NSCs supports the finding that nNOS gene expression is involved in the feedback modulation of NSC differentiation by NMDARs (Hu et al, 2008). Interestingly, several other studies using NSC cultures have suggested that NMDA activation could promote the neuronal fate determination of NSCs (Deisseroth et al, 2004;Kitayama et al, 2004;Yoneyama et al, 2008).…”

Section: Factors Regulating Nsc Differentiationmentioning

confidence: 69%

“…Interestingly, PS1/PS2 conditional double knockout was found to cause neurodegenerative stage-dependent dynamic changes. Cell proliferation was significantly enhanced at the early stages of neurodegeneration, whereas the survival of newly generated neurons was impaired during the late stages (Chen et al, 2008).…”

Section: Neurogenesis Under Pathological Conditionsmentioning

confidence: 99%

Neural stem cells: mechanisms and modeling

Yao

Gage

2012

Protein Cell

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In the adult brain, neural stem cells have been found in two major niches: the hippocampus and the olfactory bulb. Neurons derived from these stem cells contribute to learning, memory, and the autonomous repair of the brain under pathological conditions. Hence, the physiology of adult neural stem cells has become a significant component of research on synaptic plasticity and neuronal disorders. In addition, the recently developed induced pluripotent stem cell technique provides a powerful tool for researchers engaged in the pathological and pharmacological study of neuronal disorders. In this review, we briefly summarize the research progress in neural stem cells in the adult brain and in the neuropathological application of the induced pluripotent stem cell technique.

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“…In addition, NR2B-containing NMDA receptors negatively regulate neurogenesis in the adult hippocampus by activating nNOS activity. Thus, a shift toward NR2A-containing NMDA receptors in the hippocampus of MAO A/B KO mice could contribute to the enhanced neurogenesis (38).…”

Section: Mao A/b Ko Mice Showed Enhanced Contextual and Cue Memory Andmentioning

confidence: 99%

Cognitive abnormalities and hippocampal alterations in monoamine oxidase A and B knockout mice

Singh

Bortolato

Bali

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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The monoamine oxidase isoenzymes (MAOs) A and B play important roles in the homeostasis of monoaminergic neurotransmitters. The combined deficiency of MAO A and B results in significantly elevated levels of serotonin (5-hydroxytryptamine), norepinephrine, dopamine, and β-phenylethylamine; in humans and mice, these neurochemical changes are accompanied by neurodevelopmental perturbations as well as autistic-like responses. Ample evidence indicates that normal levels of monoamines in the hippocampus, amygdala, frontal cortex, and cerebellum are required for the integrity of learning and memory. Thus, in the present study, the cognitive status of MAO A/B knockout (KO) mice was examined with a wide array of behavioral tests. In comparison with male wild-type littermates, MAO A/B KO mice exhibited abnormally high and overgeneralized fear conditioning and enhanced eye-blink conditioning. These alterations were accompanied by significant increases in hippocampal long-term potentiation and alterations in the relative expression of NMDA glutamate receptor subunits. Our data suggest that chronic elevations of monoamines, because of the absence of MAO A and MAO B, cause functional alterations that are accompanied with changes in the cellular mechanisms underlying learning and memory. The characteristics exhibited by MAO A/B KO mice highlight the potential of these animals as a useful tool to provide further insight into the molecular bases of disorders associated with abnormal monoaminergic profiles.adult neurogenesis | autism-spectrum disorder | cognition M onoaminergic neurotransmitters, such as serotonin (5-HT), norepinephrine (NE), and dopamine (DA), are known to play a critical role in the modulation of mood and emotion, as well as the control of motor, perceptual, and other cognitive functions (1). Abnormal levels of these monoamines have been associated with several neuropsychiatric disorders (2-5). The enzymatic metabolism of these neurotransmitters is mainly catalyzed by monoamine oxidase (MAO), a mitochondrial-bound flavoprotein (6). The two MAO isoenzymes, A and B, are encoded by different genes next to each other on the X chromosome (7), with 70% amino acid identity (8) and identical intron-exon organization (9). MAO A has a higher affinity for 5-HT, NE, and DA (6, 10). In contrast, MAO B prefers phenylethylamine (PEA) as substrate (11), although it can degrade 5-HT, NE, and DA in the absence of MAO A (12). As a consequence, the lack of both isoenzymes in mice results in significantly higher monoamine levels than those observed in single knockout (KO) counterparts (12). The deficiency of both MAO isoenzymes in humans has been found to be associated with severe intellectual and developmental disabilities, hypotonia, failure to thrive, and autisticlike symptoms (including sociocommunicative deficits and perseverative manifestations) (13-15). Although similar alterations were also featured by MAO A KO mice, the severity of the changes was typically more pervasive in MAO A/B KO mice, supporting the idea that the se...

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Negative regulation of neurogenesis and spatial memory by NR2B‐containing NMDA receptors

Cited by 61 publications

References 75 publications

Interaction between Neurogenesis and Hippocampal Memory System: New Vistas

Interaction between Neurogenesis and Hippocampal Memory System: New Vistas

Neural stem cells: mechanisms and modeling

Cognitive abnormalities and hippocampal alterations in monoamine oxidase A and B knockout mice

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