Dynamics of endogenous Hsp70 synthesis in the brain of olfactory bulbectomized mice
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Numerous epidemiological studies have established acute brain injury as one of the major risk factors for the Alzheimer's disease (AD). However, the lack of animal models of AD-like degeneration triggered by a defined injury hampered the development of adequate therapies. Here we report that the surgical damage of the olfactory bulbs triggers the development of several pathologies, including amyloid-β accumulation and strong decrease of neuron density in the cortex and hippocampus as well as significant disturbance of spatial memory. Characteristically, these harmful consequences of the olfactory bulbectomy (OBX) have a peculiar dynamics in time with maximal manifestation in periods of 1–1.5 months and 8 months after the surgery and, hence, exhibit biphasic pattern with almost complete recovery period taking place at 5–6 months after the operation. The quantitative determination of endogenous inducible form of Hsp70 in different brain areas of OBX mice demonstrated characteristic fluctuations of Hsp70 levels depending on the time after the operation and age of mice. Interestingly, maximal induction of Hsp70 synthesis in the hippocampus exhibits clear-cut coincidence with the recovery period in OBX animals. The observed correlation enables to suggest curing effect of Hsp70 synthesis at an earlier period of pathology development and establishes it as a possible therapeutic agent for secondary grave consequences of brain injury, such as AD-like degeneration, for which neuroprotective therapy is urgently needed.
KeywordsOlfactory bulbectomy Spatial memory Neurodegeneration Hsp70 Amyloid-β (Aβ) Alzheimer’s disease
This work was supported by the grants from the Russian Foundation for Basic Research, “Genofond Dynamics” program, the Program of Presidium RAS “Fundamental Sciences to Medicine“ to N.B., I.N., N.M., A.S., and I.A., the Program of Molecular and Cellular Biology RAN to M.E., B.M., and I.G., and the NIH and from the Dynasty Foundation and BGRF (E.N.).
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