Abstract
Protein kinase B (Akt) is a key enzyme in one of many neuroprotective signaling cascades in neurons that are activated during preconditioning by episodes of moderate hypoxia/ischemia. However, the data on the involvement of this anti-apoptotic pathway in mechanisms of the hypoxic tolerance induced by different experimental protocols are incomplete and contradictory. We exposed rats to moderate hypobaric hypoxia (3MHH) corresponding to an altitude of 5000 m above sea level three times (once a day for 2 hours). The 3MHH treatment is known as an effective stimulus for hypoxic brain tolerance. We used immunocytochemistry to study the dynamics of phosphorylation of Akt caused by 3MHH in various areas of the brain. It was found that each of the three 3MHH episodes quickly (within 3 hours) activated Akt phosphorylation in the neocortex, piriform cortex, and dentate gyrus of the hippocampus. Severe hypobaric hypoxia (SHH), the equivalent of a rise to 11000 m above sea level, did not produce this effect. Behavioral experiments on 3MHH-preconditioned rats subjected to subsequent SHH have shown that blocking the activity of PI3K/Akt with wortmannin during preconditioning had an anxiogenic effect typical of non-preconditioned animals that survived the SHH. Thus, we established the details of the involvement of the PI3K/Akt pathway in the neuroprotective mechanism of 3MHH-preconditioning for the first time.
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Abbreviations
- MHH:
-
moderate hypobaric hypoxia
- 3MHH:
-
a procedure of three MHH episodes with 24 h intervals
- SHH:
-
severe hypobaric hypoxia
- Akt:
-
protein kinase B
- pAkt:
-
phosphorylated (active) Akt, PI3K, phosphoinositide 3-kinas
- EPM:
-
elevated plus maze
- NC:
-
the number of entries to closed arms
- NCO:
-
the number of entries to the central and open parts
- TCO:
-
time spent during performance of NCO
- NR:
-
the number of rearings
- OF:
-
open field
- VMA:
-
vertical motor activity
- HMA:
-
horizontal motor activity
- FD:
-
freezing duration
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Original Russian Text © A.V. Belyakov, D.G. Semenov, 2017, published in Neirokhimiya, 2017, Vol. 34, No. 3, pp. 209–217.
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Belyakov, A.V., Semenov, D.G. The PI3K/Akt system is involved in the neuroprotective preconditioning of rats with moderate hypobaric hypoxia. Neurochem. J. 11, 213–220 (2017). https://doi.org/10.1134/S1819712417020039
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DOI: https://doi.org/10.1134/S1819712417020039