TY - JOUR

T1 - Expression of Pro- and Mature Brain-Derived Neurotrophic Factor and Bcl-xL in the Hippocampus of Neonatal Rats under Dexamethasone Treatment

AU - Bulygina, V. v.

AU - Kalinina, T. s.

AU - Lanshakov, D. a.

AU - Menshanov, P. n.

AU - Suhareva, E. v.

AU - Dygalo, N. n.

N1 - Expression of Pro- and Mature Brain-Derived Neurotrophic Factor and Bcl-xL in the Hippocampus of Neonatal Rats under Dexamethasone Treatment / V. V. Bulygina, T. S. Kalinina, D. A. Lanshakov [et al.] // Neurochemical Journal. – 2024. – Vol. 18, No. 4. – P. 649-656. – DOI 10.1134/S1819712424700296. This work was supported by budget project #FWNR-2022-0023.

PY - 2025/3/18

Y1 - 2025/3/18

N2 - Due to the key role of neurotrophins in brain development and plasticity, the question of whether and how the precursor of brain-derived neurotrophic factor (proBDNF) can influence the active elimination of excess cells by apoptosis is of great importance. It was hypothesized that proneurotrophins selectively activate the neurotropin receptor p75, thereby inducing proapoptotic signaling pathways, while mature BDNF (matBDNF) has an antiapoptotic effect. Rationale: proBDNF and matBDNF will exhibit specific expression patterns that modify the process of glucocorticoid-induced apoptosis in the brain of neonatal rats. Thus, the study examined the effect of the glucocorticoid dexamethasone (DEX) on the levels of mRNA of BDNF and the key protease of apoptosis caspase-3, the number of cells expressing active caspase-3, as well as the proteins proBDNF, matBDNF and the key anti-apoptotic protein BCL-xL in the hippocampus of 3–4 day old rat pups in 6 or 24 hours after DEX administration. After 6 hours, DEX induced anti-apoptotic processes, namely, it increased the levels of bdnf mRNA in the whole hippocampus, as well as the content of matBDNF and Bcl-xL proteins in the CA1-3 fields and the dentate gyrus. In this case, a temporary predominance of matBDNF expression over apoptogenic proBDNF was formed against the background of a constant number of cells expressing active caspase-3. In 24 hours, DEX provoked an increase in the expression of apoptogenic proBDNF, and its prevalence over mature neurotrophin in all fields of the hippocampus, accompanied by an increase in the number of cells, expressing active caspase-3. Moreover, we found a significant correlation between the proBDNF/matBDNF ratio and active caspase-3 in all three areas of the hippocampus. It has been shown that proBDNF has its own expression pattern different from its mature form in the hippocampus of neonatal rats upon DEX induction and the manifestation of its proapoptotic effect is accompanied by an increase in the proBDNF/matBDNF ratio.

AB - Due to the key role of neurotrophins in brain development and plasticity, the question of whether and how the precursor of brain-derived neurotrophic factor (proBDNF) can influence the active elimination of excess cells by apoptosis is of great importance. It was hypothesized that proneurotrophins selectively activate the neurotropin receptor p75, thereby inducing proapoptotic signaling pathways, while mature BDNF (matBDNF) has an antiapoptotic effect. Rationale: proBDNF and matBDNF will exhibit specific expression patterns that modify the process of glucocorticoid-induced apoptosis in the brain of neonatal rats. Thus, the study examined the effect of the glucocorticoid dexamethasone (DEX) on the levels of mRNA of BDNF and the key protease of apoptosis caspase-3, the number of cells expressing active caspase-3, as well as the proteins proBDNF, matBDNF and the key anti-apoptotic protein BCL-xL in the hippocampus of 3–4 day old rat pups in 6 or 24 hours after DEX administration. After 6 hours, DEX induced anti-apoptotic processes, namely, it increased the levels of bdnf mRNA in the whole hippocampus, as well as the content of matBDNF and Bcl-xL proteins in the CA1-3 fields and the dentate gyrus. In this case, a temporary predominance of matBDNF expression over apoptogenic proBDNF was formed against the background of a constant number of cells expressing active caspase-3. In 24 hours, DEX provoked an increase in the expression of apoptogenic proBDNF, and its prevalence over mature neurotrophin in all fields of the hippocampus, accompanied by an increase in the number of cells, expressing active caspase-3. Moreover, we found a significant correlation between the proBDNF/matBDNF ratio and active caspase-3 in all three areas of the hippocampus. It has been shown that proBDNF has its own expression pattern different from its mature form in the hippocampus of neonatal rats upon DEX induction and the manifestation of its proapoptotic effect is accompanied by an increase in the proBDNF/matBDNF ratio.

UR - https://www.elibrary.ru/item.asp?id=80497964

U2 - 10.1134/S1819712424700296

DO - 10.1134/S1819712424700296

M3 - Article

VL - 18

SP - 649

EP - 656

JO - Neurochemical Journal

JF - Neurochemical Journal

SN - 1819-7124

IS - 4

ER -