Journal Article Epublish 1 citation
PubMed: 40299680 DOI: 10.3390/biomedicines13040982
HSP Modulators for the Correction of Cognitive, Mnemonic, and Behavioral Disorders After Prenatal Hypoxia.
Biomedicines 13(4)
Authors: Olena Aliyeva, Igor F Belenichev, Ivan Bilai, Iryna Duiun, Lyudmyla Makyeyeva, Valentyn Oksenych, Oleksandr Kamyshnyi
Affiliations
- Department of Histology, Cytology and Embryology, Zaporizhzhia State Medical and Pharmaceutical University, 69035 Zaporizhzhia, Ukraine.
- Department of Pharmacology and Medical Formulation with Course of Normal Physiology, Zaporizhzhia State Medical and Pharmaceutical University, 69035 Zaporizhzhia, Ukraine.
- Department of Clinical Pharmacy, Pharmacotherapy, Pharmacognosy and Pharmaceutical Chemistry, Zaporizhzhia State Medical and Pharmaceutical University, 69035 Zaporizhzhia, Ukraine.
- Faculty of Medicine, University of Bergen, 5020 Bergen, Norway.
- Department of Microbiology, Virology, and Immunology, I. Horbachevsky Ternopil National Medical University, 46001 Ternopil, Ukraine.
Abstract
Prenatal hypoxia (PH) is a leading cause of nervous system disorders in early childhood and subsequently leads to a decline in the cognitive and mnemonic functions of the central nervous system (such as memory impairment, reduced learning ability, and information processing). It also increases anxiety and the risk of brain disorders in adulthood. Compensatory-adaptive mechanisms of the mother-placenta-fetus system, which enhance the fetus's CNS resilience, are known, including the activation of endogenous neuroprotection in response to hypoxic brain injury through the pharmacological modulation of HSP. To evaluate the effect of HSP modulators-Cerebrocurin, Angiolin, Tamoxifen, Glutaredoxin, Thiotriazoline, and HSF-1 (heat shock factor 1 protein), as well as Mildronate and Mexidol-on the motor skills, exploratory behaviors, psycho-emotional activities, learning, and memories of offspring after PH. Experimental PH was induced by daily intraperitoneal injections of sodium nitrite solution into pregnant female rats from the 16th to the 21st day of pregnancy at a dose of 50 mg/kg. The newborns received intraperitoneal injections of Angiolin (50 mg/kg), Thiotriazoline (50 mg/kg), Mexidol (100 mg/kg), Cerebrocurin (150 µL/kg), L-arginine (200 mg/kg), Glutaredoxin (200 µg/kg), HSF-1 (50 mg/kg), or Mildronate (50 mg/kg) for 30 days. At 1 month, the rats were tested in the open field test, and at 2 months, they were trained and tested for working and spatial memory in the radial maze. Modeling PH led to persistent impairments in exploratory activity, psycho-emotional behavior, and a decrease in the cognitive-mnestic functions of the CNS. It was found that Angiolin and Cerebrocurin had the most pronounced effects on the indicators of exploratory activity and psycho-emotional status in 1-month-old animals after PH. They also exhibited the most significant cognitive-enhancing and memory-supporting effects during the training and evaluation of skill retention in the maze in 2-month-old offspring after PH. for the first time, we obtained experimental data on the effects of HSP modulators on exploratory activity, psycho-emotional behavior, and cognitive-mnestic functions of the central nervous system in offspring following intrauterine hypoxia. Based on the results of this study, we identified the pharmacological agents Angiolin and Cerebrocurin as promising neuroprotective agents after perinatal hypoxia.
MeSH
Injections, Memory Disorders, Arginine, Injections, Intraperitoneal, Brain, Central Nervous System, Hypoxia, Open Field Test, Nervous System, Learning, Memory, Fetus