Effect of the Inhibitory Neurotransmitter Glycine on Slow Destructive Processes in Brain Cortex Slices under Anoxic Conditions

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A. A. Tonshin¹, N. V. Lobysheva^1,2, L. S. Yaguzhinsky^1*, E. N. Bezgina³, D. A. Moshkov³, and Ya. R. Nartsissov²

¹Belozersky Research Institute for Physico-Chemical Biology, Lomonosov Moscow State University, 119992 Moscow, Russia; fax: (495) 939-0338; E-mail: yag@genebee.msu.su

²Research Institute of Cytochemistry and Molecular Pharmacology, ul. 6-ya Radialnaya 24, Build. 14, 115404 Moscow, Russia

³Research Institute of Theoretical and Experimental Biophysics, Russian Academy of Sciences, ul. Institutskaya 4, 142290 Pushchino, Moscow Region, Russia

^* To whom correspondence should be addressed.

Received June 27, 2006; Revision received December 29, 2006

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Slow destructive processes in brain cortex were studied under deep hypoxia (anoxia). Study of the character and dynamics of DNA destruction showed that apoptosis and necrosis run in parallel under the experimental conditions. These processes typically develop in tens of hours. A similar conclusion was reached from electron microscopic study of the tissue ultrastructure. More detailed study revealed that a relatively rare type of apoptosis not involving cytochrome c release from the intermembrane space of mitochondria and not associated with opening of the mitochondrial nonspecific pore occurs under the experimental conditions. As this is occurring, the process can be slowed by high concentrations of glycine, an inhibitory neurotransmitter. The study of DNA destruction demonstrated that high concentrations of glycine selectively slow apoptosis but have almost no effect on necrosis. Glycine also drastically decreases changes in the tissue ultrastructure, particularly of mitochondria, arising under anoxia. Glycine does not notably influence the mitochondrial oxidative phosphorylation system. Study of impairment of mitochondrial function demonstrated that the oxidative phosphorylation system is not disturbed for 1 h, which is several times longer than the inhibition time of brain function under deep hypoxia. The mitochondrial respiratory system is preserved for a relatively long time (24 h). Malate oxidase activity is deactivated after 48 h. The succinate oxidase fragment of the mitochondrial respiratory chain proved especially resistant; it retains activity under anoxia for more than 72 h. A possible mechanism of the effect of high glycine concentrations is discussed.

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KEY WORDS: brain cortex tissue, glycine, mitochondrion, apoptosis, necrosis, anoxia

DOI: 10.1134/S0006297907050070

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