Regulation of Neprilysin Activity and Cognitive Functions in Rats After Prenatal Hypoxia

Журавин, И. А.; Dubrovskaya, N. М.; Vasilev, D. S.; Козлова, Д. И.; Kochkina, E. G.; Туманова, Н. Л.; Nalivaeva, Natalia N.

doi:10.1007/s11064-019-02796-3

Cited by 19 publications

(15 citation statements)

References 69 publications

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“…As already mentioned above, NEP expression and activity decrease with age in some peripheral tissues and in brain structures of experimental animals ( Kletsas et al, 1998 ; Nalivaeva et al, 2004 ; Zhuravin et al, 2019 ). There are also several studies reporting that in human brain, and especially in the hippocampus, which is vulnerable to AD pathology, NEP steady-state levels diminish as a function of age ( Caccamo et al, 2005 ).…”

Section: Nep In the Ageing Brainmentioning

confidence: 66%

“…Several studies from our laboratory have demonstrated that prenatal hypoxia in rats results in a significant reduction of NEP mRNA and protein levels and its enzyme activity in the cortex and hippocampus of rat offspring which correlates with a reduced number of dendritic spines in these brain structures and cognitive impairment of animals during postnatal development and can predispose to development of neurodegeneration, including AD, in later life ( Fig. 3 ) ( Nalivaeva et al, 2018 ; Zhuravin et al, 2019 ). On the other hand, NEP levels in postnatal life were shown to be dependent on the environment in which animals have been raised and elevated NEP activity was reported in the brains of mice raised in an "enriched environment" which inversely correlated with the amyloid burden ( Lazarov et al, 2005 ).…”

Section: Nep In Development Of the Nervous Systemmentioning

confidence: 99%

“…Intracranial injections to rats, subjected to prenatal hypoxia, of a caspase-3 inhibitor (Z-DEVD-FMK or Ac-DEVD-CHO) at the age of three weeks reduced caspase activity and restored AICD levels and NEP protein expression ( Vasilev et al, 2016 ; Kozlova et al, 2015 ). Moreover, administration of an HDAC inhibitor, sodium valproate, or the antioxidant EGCG were shown to increase NEP expression and activity in rats subjected to prenatal hypoxia ( Nalivaeva et al, 2012b ; Zhuravin et al, 2019 ).…”

Section: Role Of Nep In Diseasesmentioning

confidence: 99%

See 2 more Smart Citations

Neprilysin expression and functions in development, ageing and disease

Наливаева

Журавин

Turner

2020

Mechanisms of Ageing and Development

121

103

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Section: Nep In the Ageing Brainmentioning

confidence: 66%

Section: Nep In Development Of the Nervous Systemmentioning

confidence: 99%

Section: Role Of Nep In Diseasesmentioning

confidence: 99%

See 1 more Smart Citation

Neprilysin expression and functions in development, ageing and disease

Наливаева

Журавин

Turner

2020

Mechanisms of Ageing and Development

121

103

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show abstract

“…Possible insults downregulating MME include hypoxia and NF-κB (nuclear factor kappa B) signaling. In rodents, hypoxia downregulates MME expression in the lungs, kidneys [20], and in the brain [21]. In fact, several studies have revealed a subtle hypoxic fetal environment in pregnancy complicated by maternal overweight [29,30].…”

Section: Discussionmentioning

confidence: 99%

“…Hypoxia and NF-κB (nuclear factor kappa B) signalling downregulate MME in other cell types [19][20][21], and TNFα (tumor necrosis factor α) is an activator of NF-κB signaling [22]. Thus, we tested whether oxygen or TNFα altered MME in fpEC from control pregnancies.…”

Section: Mme Protein In Fpec Was Not Regulated By Oxygen and Tumor Nementioning

confidence: 99%

Maternal Overweight Downregulates MME (Neprilysin) in Feto-Placental Endothelial Cells and in Cord Blood

Weiss

Berger

Brandl

et al. 2020

IJMS

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Maternal overweight in pregnancy alters the metabolic environment and generates chronic low-grade inflammation. This affects fetal development and programs the offspring’s health for developing cardiovascular and metabolic disease later in life. MME (membrane-metalloendopeptidase, neprilysin) cleaves various peptides regulating vascular tone. Endothelial cells express membrane-bound and soluble MME. In adults, the metabolic environment of overweight and obesity upregulates endothelial and circulating MME. We here hypothesized that maternal overweight increases MME in the feto-placental endothelium. We used primary feto-placental endothelial cells (fpEC) isolated from placentas after normal vs. overweight pregnancies and determined MME mRNA, protein, and release. Additionally, soluble cord blood MME was analyzed. The effect of oxygen and tumor necrosis factor α (TNFα) on MME protein in fpEC was investigated in vitro. Maternal overweight reduced MME mRNA (−39.9%, p < 0.05), protein (−42.5%, p = 0.02), and MME release from fpEC (−64.7%, p = 0.02). Both cellular and released MME protein negatively correlated with maternal pre-pregnancy BMI. Similarly, cord blood MME was negatively associated with pre-pregnancy BMI (r = −0.42, p = 0.02). However, hypoxia and TNFα, potential negative regulators of MME expression, did not affect MME protein. Reduction of MME protein in fpEC and in cord blood may alter the balance of vasoactive peptides. Our study highlights the fetal susceptibility to maternal metabolism and inflammatory state.

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Cerebral Hypoxia-Induced Molecular Alterations and Their Impact on the Physiology of Neurons and Dendritic Spines: A Comprehensive Review

Cui,

Jiang,

Wang

et al. 2024

Cell Mol Neurobiol

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This article comprehensively reviews how cerebral hypoxia impacts the physiological state of neurons and dendritic spines through a series of molecular changes, and explores the causal relationship between these changes and neuronal functional impairment. As a severe pathological condition, cerebral hypoxia can significantly alter the morphology and function of neurons and dendritic spines. Specifically, dendritic spines, being the critical structures for neurons to receive information, undergo changes such as a reduction in number and morphological abnormalities under hypoxic conditions. These alterations further affect synaptic function, leading to neurotransmission disorders. This article delves into the roles of molecular pathways like MAPK, AMPA receptors, NMDA receptors, and BDNF in the hypoxia-induced changes in neurons and dendritic spines, and outlines current treatment strategies. Neurons are particularly sensitive to cerebral hypoxia, with their apical dendrites being vulnerable to damage, thereby affecting cognitive function. Additionally, astrocytes and microglia play an indispensable role in protecting neuronal and synaptic structures, regulating their normal functions, and contributing to the repair process following injury. These studies not only contribute to understanding the pathogenesis of related neurological diseases but also provide important insights for developing novel therapeutic strategies. Future research should further focus on the dynamic changes in neurons and dendritic spines under hypoxic conditions and their intrinsic connections with cognitive function.

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Regulation of Neprilysin Activity and Cognitive Functions in Rats After Prenatal Hypoxia

Cited by 19 publications

References 69 publications

Neprilysin expression and functions in development, ageing and disease

Neprilysin expression and functions in development, ageing and disease

Maternal Overweight Downregulates MME (Neprilysin) in Feto-Placental Endothelial Cells and in Cord Blood

Cerebral Hypoxia-Induced Molecular Alterations and Their Impact on the Physiology of Neurons and Dendritic Spines: A Comprehensive Review

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