Levels of Thyroid Hormones and Indices of Energy Metabolism in the Cerebral Cortex of Rats with Experimental Alzheimer’s Disease
- 13 Downloads
The study was carried out on 30 mature WAG rats, 15 intact control animals and 15 rats with modeled Alzheimer’s disease (AD) induced by course injections of scopolamine (27 days, 1 mg/kg, i.p. daily). The contents of ATP, glucose, pyruvate, and lactate were measured spectrophotometrically in homogenates of the brain cortex of the animals. The levels of TSH, T3, and T4 in blood serum and those of T3 and T4 in cortex homogenates were estimated using ELISA. The activities of pyruvate dehydrogenase, creatine phosphokinase, and key enzymes of the tricarboxylic acid cycle (TCA) were measured in the mitochondria using a spectrophotometric technique. It was found that the content of T3 in the brain cortex of rats was much lower than in the controls against the background of higher T4 concentrations, which was indicative of the development of local hypothyroidism in the brain. The increased activity of pyruvate dehydrogenase against the background of low activities of TCA cycle enzymes in brain homogenates was observed. The decreased creatine kinase activity and low ATP contents were also found. Local hypothyroidism in the brain cortex is believed to be one of the significant factors inducing the development of strong energy deficiency and reducing the activity of Krebs cycle enzymes. Consequently, this contributes to the death of neurons in experimental AD in rats.
KeywordsAlzheimer’s disease scopolamine energy metabolism thyroid hormones ATP rats
Unable to display preview. Download preview PDF.
- 5.J. Z. Wang, Y. Y. Xia, I. Grundke-Iqbal, and K. Iqbal, “Abnormal hyperphosphorylation of tau: sites, regulation, and molecular mechanism of neurofibrillary degeneration,” J. Alzheimer`s Dis., 33, Suppl. 1, 123-139 (2013).Google Scholar
- 6.M. Kolarova, F. García-Sierra, A. Bartos, et al., “Structure and pathology of tau protein in Alzheimer disease,” Int. J. Alzheimer`s Dis., 731526; doi: 10.1155/2012/731526 (2012).Google Scholar
- 10.A. N. Mironova, Manual for Carrying Out Preclinical Studies of Pharmacological Agents, Part 1, Grif and Co., Moscow (2012).Google Scholar
- 11.R. D. Deyko, C. Yu. Shtrygol’, T. V. Gorbach, et al., “Nootropic properties of a tetrapeptide, Acetyl-(DLys)-Lys-Arg-Arg-Amide (KK-1), in a rat model of Alzheimer’s disease induced by chronic introduction of scopolamine,” Klin. Farmats., 20, No. 4, 52-61 (2016).Google Scholar
- 12.M. I. Prokhorova, Methods of Biochemical Studies (Lipid and Energetic Metabolism), Publ. House of the Leningrad University, Leningrad (1982).Google Scholar
- 18.J. H. Duncan Bassett, “Thyroid hormone action: Genomic and non-genomic effects,” Endocrine Abstr., 25, S6.1 (2011).Google Scholar