Regional Immunoreactivity of Pax6 in the Neurogenic Zone After Chronic Prenatal Hypoxia

So, Keum Young; Chung, Yoon-Young; Yu, Sun‐Kyoung; Jun, Yonghyun

doi:10.21873/invivo.11178

Cited by 10 publications

(8 citation statements)

References 33 publications

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“…Importantly, it was also shown that prenatal hypoxia affects the cells in brain neurogenic zones and, in particular, the levels of expression of the protein paired box 6 (Pax6) which plays an important role in neurogenesis, cell proliferation, differentiation and survival during the development of the central nervous system (Simpson and Price, 2002 ). Although in the fetuses subjected to prenatal hypoxia the levels of Pax6 were increased in the subventricular zone and subgranular zone of the hippocampal dentate gyrus, they were significantly decreased in the cerebral cortex (So et al, 2017 ). This finding correlates with the reduced number of neuronal cells in rat cortex during the first month of postnatal life observed in our studies (Vasiliev et al, 2008 ).…”

Section: Prenatal Hypoxia In Ratsmentioning

confidence: 99%

Role of Prenatal Hypoxia in Brain Development, Cognitive Functions, and Neurodegeneration

2018

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This review focuses on the role of prenatal hypoxia in the development of brain functions in the postnatal period and subsequent increased risk of neurodegenerative disorders in later life. Accumulating evidence suggests that prenatal hypoxia in critical periods of brain formation results in significant changes in development of cognitive functions at various stages of postnatal life which correlate with morphological changes in brain structures involved in learning and memory. Prenatal hypoxia also leads to a decrease in brain adaptive potential and plasticity due to the disturbance in the process of formation of new contacts between cells and propagation of neuronal stimuli, especially in the cortex and hippocampus. On the other hand, prenatal hypoxia has a significant impact on expression and processing of a variety of genes involved in normal brain function and their epigenetic regulation. This results in changes in the patterns of mRNA and protein expression and their post-translational modifications, including protein misfolding and clearance. Among proteins affected by prenatal hypoxia are a key enzyme of the cholinergic system-acetylcholinesterase, and the amyloid precursor protein (APP), both of which have important roles in brain function. Disruption of their expression and metabolism caused by prenatal hypoxia can also result, apart from early cognitive dysfunctions, in development of neurodegeneration in later life. Another group of enzymes affected by prenatal hypoxia are peptidases involved in catabolism of neuropeptides, including amyloid-β peptide (Aβ). The decrease in the activity of neprilysin and other amyloid-degrading enzymes observed after prenatal hypoxia could result over the years in an Aβ clearance deficit and accumulation of its toxic species which cause neuronal cell death and development of neurodegeneration. Applying various approaches to restore expression of neuronal genes disrupted by prenatal hypoxia during postnatal development opens an avenue for therapeutic compensation of cognitive dysfunctions and prevention of Aβ accumulation in the aging brain and the model of prenatal hypoxia in rodents can be used as a reliable tool for assessment of their efficacy.

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Section: Prenatal Hypoxia In Ratsmentioning

confidence: 99%

Role of Prenatal Hypoxia in Brain Development, Cognitive Functions, and Neurodegeneration

2018

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“…A prolonged hypoxia state may result in ischemia followed by neuronal death and reduction of neuronal density [ 1 ]. Interestingly, hypoxia can also trigger neurogenesis within the surrounding tissue [ 2 , 3 ] prenatally as well as postpartum [ 4 , 5 ]. Neurogenesis in the adult brain is essential and occurs during the entire postnatal life.…”

Section: Introductionmentioning

confidence: 99%

Ghrelin Regulates Expression of the Transcription Factor Pax6 in Hypoxic Brain Progenitor Cells and Neurons

Stoyanova

Klymenko

Willms

et al. 2022

Cells

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The nature of brain impairment after hypoxia is complex and recovery harnesses different mechanisms, including neuroprotection and neurogenesis. Experimental evidence suggests that hypoxia may trigger neurogenesis postnatally by influencing the expression of a variety of transcription factors. However, the existing data are controversial. As a proof-of-principle, we subjected cultured cerebral cortex neurons, cerebellar granule neurons and organotypic cerebral cortex slices from rat brains to hypoxia and treated these cultures with the hormone ghrelin, which is well-known for its neuroprotective functions. We found that hypoxia elevated the expression levels and stimulated nuclear translocation of ghrelin’s receptor GHSR1 in the cultured neurons and the acute organotypic slices, whereas ghrelin treatment reduced the receptor expression to normoxic levels. GHSR1 expression was also increased in cerebral cortex neurons of mice with induced experimental stroke. Additional quantitative analyses of immunostainings for neuronal proliferation and differentiation markers revealed that hypoxia stimulated the proliferation of neuronal progenitors, whereas ghrelin application during the phase of recovery from hypoxia counteracted these effects. At the mechanistic level, we provide a link between the described post-ischemic phenomena and the expression of the transcription factor Pax6, an important regulator of neural progenitor cell fate. In contrast to the neurogenic niches in the brain where hypoxia is known to increase Pax6 expression, the levels of the transcription factor in cultured hypoxic cerebral cortex cells were downregulated. Moreover, the application of ghrelin to hypoxic neurons normalised the expression levels of these factors. Our findings suggest that ghrelin stimulates neurogenic factors for the protection of neurons in a GHSR1-dependent manner in non-neurogenic brain areas such as the cerebral cortex after exposure to hypoxia.

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“…Rats and mice are the most popular and convenient rodent models, and both can be used in prenatal hypoxia studies. In rats, when hypoxia was induced by unilateral uterine artery ligation on the 16th day of pregnancy, Pax6, which plays an important role in neurogenesis, showed diverse patterns in the neurogenic zone ( So et al, 2017 ). In addition, different rat models of prenatal hypoxia showed different degrees of learning and memory deficits ( Cai et al, 1999 ; Dubrovskaia and Zhuravin, 2008 ; Delcour et al, 2012b ; Vasilev et al, 2016 ; Wei et al, 2016 ; Sosedova et al, 2019 ; Zhuravin et al, 2019 ; Jia et al, 2020 ).…”

Section: Prenatal Hypoxiamentioning

confidence: 99%

Effects of Prenatal Hypoxia on Nervous System Development and Related Diseases

et al. 2021

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The fetal origins of adult disease (FOAD) hypothesis, which was proposed by David Barker in the United Kingdom in the late 1980s, posited that adult chronic diseases originated from various adverse stimuli in early fetal development. FOAD is associated with a wide range of adult chronic diseases, including cardiovascular disease, cancer, type 2 diabetes and neurological disorders such as schizophrenia, depression, anxiety, and autism. Intrauterine hypoxia/prenatal hypoxia is one of the most common complications of obstetrics and could lead to alterations in brain structure and function; therefore, it is strongly associated with neurological disorders such as cognitive impairment and anxiety. However, how fetal hypoxia results in neurological disorders remains unclear. According to the existing literature, we have summarized the causes of prenatal hypoxia, the effects of prenatal hypoxia on brain development and behavioral phenotypes, and the possible molecular mechanisms.

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Regional Immunoreactivity of Pax6 in the Neurogenic Zone After Chronic Prenatal Hypoxia

Cited by 10 publications

References 33 publications

Role of Prenatal Hypoxia in Brain Development, Cognitive Functions, and Neurodegeneration

Role of Prenatal Hypoxia in Brain Development, Cognitive Functions, and Neurodegeneration

Ghrelin Regulates Expression of the Transcription Factor Pax6 in Hypoxic Brain Progenitor Cells and Neurons

Effects of Prenatal Hypoxia on Nervous System Development and Related Diseases

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