Role of prenatal hypoxia in development of neurodegeneration-prone phenotype

• Autorzy: Nalivaeva N.N. , Zhuravin I.A.
• Języki publikacji: EN

Abstrakty

EN

Accumulating evidence suggests that prenatal hypoxia (PH) in critical periods of brain formation results in numerous changes in brain functioning at various stages of postnatal life. They involve morphological changes in brain structures involved in learning and memory as well as a decrease in brain adaptive potential and plasticity caused by disturbances in the process of formation of new contacts between cellular populations. In particular, PH decreases the number of labile dendritic spines in the cortex and hippocampus which underlie brain plasticity. This is underlined by epigenetic effects of PH on expression and processing of a variety of genes involved in normal brain development and functioning. Among proteins affected by PH is the major enzyme of the cholinergic system – acetylcholinesterase, and amyloid precursor protein, which have important roles in various brain functions. Disruption of their expression and metabolism caused by PH can result in both early cognitive dysfunctions and development of neurodegeneration in later life. Another group of enzymes involved in catabolism of neuropeptides, including amyloid‑β peptide (Aβ) are also affected by PH. The decrease in the activity of neprilysin and insulin-degrading enzyme as well as of transport protein transthyretin after PH over the years could result in Aβ clearance deficit and accumulation of its toxic species causing neuronal cell death and development of neurodegeneration. PH also results in activation of brain caspases which affect numerous cellular events. Applying various approaches to restore expression of neuronal genes disrupted by PH during postnatal development opens an avenue for therapeutic compensation of cognitive dysfunctions and prevention of Aβ accumulation in ageing brain and the model of PH in rodents can be used as a reliable tool for assessment of their efficacy. FINANCIAL SUPPORT: Supported by ARUK, RFBR 16-04-00694, Russia state budget (01201351571).

• Wydawca: -
• Czasopismo: Acta Neurobiologiae Experimentalis
• Rocznik: 2017
• Tom: 77
• Numer: Suppl.1
• Opis fizyczny: p.21

Twórcy

autor

Nalivaeva N.N.

• I.M. Sechenov Institute of Evolutionary Physiology and Biochemistry of Russian Academy of Science, St. Petersburg, Russia
• School of Biomedical Sciences, University of Leeds, Leeds, UK

autor

Zhuravin I.A.

• I.M. Sechenov Institute of Evolutionary Physiology and Biochemistry of Russian Academy of Science, St. Petersburg, Russia
• Saint Petersburg State Pediatric Medical University, St. Petersburg, Russia