Mitoptosis is a non-return point in formation dark degenerative neurons during acute experimental endotoxemia

Abstract

Recent studies have described the significant role of inflammation in progressive nature of neurodegeneration. However, there is no unanimous opinion on the mechanism and forms of ultrastructural changes in the neurons of the cerebral cortex. Acute experimental endotoxemia was induced by intravenous injection of purified LPS from E. coli (serotype 0111:B4) at a dose of 1,0 mg/kg dissolved in saline (0,5 ml). Under deep anesthesia the cerebral cortex was removed and then processed using standard EM. Ultra thin sections from the cerebral cortex were examined by using TEM. In the state of endotoxemia, in one visual field of the cerebral cortex of the white rat, dark deformed neurons are seen in various stages of degeneration along with bright neurons. In the initial stage of formation of dark neurons, along with strong dehydration, destruction of the nuclear pore complex, expansion of the perinuclear spaces and the lumen of cisterns of the endoplasmic reticulum are observed. Between the latter there are numerous free ribosomes and mitochondria without visible ultrastructural changes (Fig. 1A). Later, if the outer membrane is preserved, the lysis of the mitochondrial cristae occurs (Fig. 1B). From this moment, except some secondary lysosomes and residues of condensed nucleoli, other organelles and cytoskeleton elements are not detected in the cytoplasm of dark neurons (Fig. 1C). Internal mitoptosis - starting with the destruction of the integrity of the mitochondrial cristae is the point of no return during the formation of degenerative dark neurons without ultrastructural signs of apoptosis.