Synaptogenesis in the developing mouse visual cortex

Li, Mingshan; Cui, Zhanjun; Niu, Yanli; Liu, Bin; Fan, Wei; Yu, Dong‐Ming; Deng, Jian

doi:10.1016/j.brainresbull.2009.08.028

Cited by 71 publications

(76 citation statements)

References 37 publications

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“…S3). Our finding that GPT2 expression reaches highest levels in the early postnatal period both in human and in mouse brain, concurrent with peaks in synaptogenesis (17,18,25), suggests a role in this process. We also observe decreases in brain growth postnatally both in human and in mouse.…”

Section: ) (D)mentioning

confidence: 70%

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Mutations in mitochondrial enzyme GPT2 cause metabolic dysfunction and neurological disease with developmental and progressive features

Ouyang

Nakayama

Baytaş

et al. 2016

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

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Mutations that cause neurological phenotypes are highly informative with regard to mechanisms governing human brain function and disease. We report autosomal recessive mutations in the enzyme glutamate pyruvate transaminase 2 (GPT2) in large kindreds initially ascertained for intellectual and developmental disability (IDD). GPT2 [also known as alanine transaminase 2 (ALT2)] is one of two related transaminases that catalyze the reversible addition of an amino group from glutamate to pyruvate, yielding alanine and α-ketoglutarate. In addition to IDD, all affected individuals show postnatal microcephaly and ∼80% of those followed over time show progressive motor symptoms, a spastic paraplegia. Homozygous nonsense p.Arg404* and missense p.Pro272Leu mutations are shown biochemically to be loss of function. The GPT2 gene demonstrates increasing expression in brain in the early postnatal period, and GPT2 protein localizes to mitochondria. Akin to the human phenotype, Gpt2-null mice exhibit reduced brain growth. Through metabolomics and direct isotope tracing experiments, we find a number of metabolic abnormalities associated with loss of Gpt2. These include defects in amino acid metabolism such as low alanine levels and elevated essential amino acids. Also, we find defects in anaplerosis, the metabolic process involved in replenishing TCA cycle intermediates. Finally, mutant brains demonstrate misregulated metabolites in pathways implicated in neuroprotective mechanisms previously associated with neurodegenerative disorders. Overall, our data reveal an important role for the GPT2 enzyme in mitochondrial metabolism with relevance to developmental as well as potentially to neurodegenerative mechanisms.GPT2 | intellectual and developmental disability | mitochondria | metabolomics | spastic paraplegia

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Section: ) (D)mentioning

confidence: 70%

“…S4B). Based on these data, peak levels of GPT2 expression correlate with major periods of synaptogenesis and myelination in both mouse and human developing postnatal brain (16)(17)(18)(19).…”

Section: Gpt2 Expression Increases In Postnatal Developingmentioning

confidence: 89%

Mutations in mitochondrial enzyme GPT2 cause metabolic dysfunction and neurological disease with developmental and progressive features

Ouyang

Nakayama

Baytaş

et al. 2016

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

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“…Using Aldh1L1-EGFP BAC-transgenic mice, in which all astrocytes express EGFP 9 , we found that astrocytic coverage of V1 neuropil profoundly increased from P7 to P21 (Fig. 1a-c), coinciding with high rates of synaptogenesis 10 . This increase correlated with the appearance of fine astrocytic processes (Extended Data Fig.…”

mentioning

confidence: 93%

Astrocytic neuroligins control astrocyte morphogenesis and synaptogenesis

Stogsdill

Ramirez

Liu

et al. 2017

Nature

396

413

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Astrocytes are highly complex glial cells with numerous fine cellular processes which infiltrate the neuropil to interact with synapses. The mechanisms controlling the establishment of astrocytes’ remarkable morphology and how impairing astrocytic infiltration of the neuropil alters synaptic connectivity are largely unknown. Here we find that cortical astrocyte morphogenesis depends on direct contact with neuronal processes and occurs in tune with the growth and activity of synaptic circuits. Neuroligin (NL) family cell adhesion proteins, NL1, NL2, and NL3, which are expressed by cortical astrocytes, control astrocyte morphogenesis through interactions with neuronal neurexins. Furthermore, in the absence of astrocytic NL2, cortical excitatory synapse formation and function is diminished, whereas inhibitory synaptic function is enhanced. Our findings highlight a novel mechanism of action for NLs and link astrocyte morphogenesis to synaptogenesis. Because NL mutations are implicated in various neurological disorders, these findings also offer an astrocyte-based mechanism of neural pathology.

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“…This process occurs over the first 3 postnatal weeks of life in rodents and through adolescence in humans (Rice, 2000). Synaptic junctions in the mature brain are predominantly located on dendritic spines and mature synaptic structures do not appear until day of life 7 in mice (Li, 2010). Thereafter, synaptic structures are easily identified (Li, 2010).…”

Section: Vulnerability Of the Developing Brainmentioning

confidence: 99%

“…Synaptic junctions in the mature brain are predominantly located on dendritic spines and mature synaptic structures do not appear until day of life 7 in mice (Li, 2010). Thereafter, synaptic structures are easily identified (Li, 2010). Neurogenesis, neurite outgrowth, and formation of synapses are critical for establishing neuronal connections in the developing brain (Li, 2010).…”

Section: Vulnerability Of the Developing Brainmentioning

confidence: 99%

Carbon monoxide pollution and neurodevelopment: A public health concern

Levy¹

2015

Neurotoxicology and Teratology

119

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Although an association between air pollution and adverse systemic health effects has been known for years, the effect of pollutants on neurodevelopment has been underappreciated. Recent evidence suggests a possible link between air pollution and neurocognitive impairment and behavioral disorders in children, however, the exact nature of this relationship remains poorly understood. Infants and children are uniquely vulnerable due to the potential for exposure in both the fetal and postnatal environments during critical periods in development. Carbon monoxide (CO), a common component of indoor and outdoor air pollution, can cross the placenta to gain access to the fetal circulation and the developing brain. Thus, CO is of particular interest as a known neurotoxin and a potential public health threat. Here we review overt CO toxicity and the policies regulating CO exposure, detail the evidence suggesting a potential link between CO-associated ambient air pollution, tobacco smoke, and learning and behavioral abnormalities in children, describe the effects of subclinical CO exposure on the brain during development, and provide mechanistic insight into a potential connection between CO exposure and neurodevelopmental outcome. CO can disrupt a number of critical processes in the developing brain, providing a better understanding of how this specific neurotoxin may impair neurodevelopment. However, further investigation is needed to better define the effects of perinatal CO exposure on the immature brain. Current policies regarding CO standards were established based on evidence of cardiovascular risk in adults with pre-existing comorbidities. Thus, recent and emerging data highlighted in this review regarding CO exposure in the fetus and developing child may be important to consider when the standards and guidelines are evaluated and revised in the future.

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Synaptogenesis in the developing mouse visual cortex

Cited by 71 publications

References 37 publications

Mutations in mitochondrial enzyme GPT2 cause metabolic dysfunction and neurological disease with developmental and progressive features

Mutations in mitochondrial enzyme GPT2 cause metabolic dysfunction and neurological disease with developmental and progressive features

Astrocytic neuroligins control astrocyte morphogenesis and synaptogenesis

Carbon monoxide pollution and neurodevelopment: A public health concern

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