Effect of Cholestasis on Cholinergic Neurons of Cingulate Cortex in Rats

Cholestasis, characterized by stagnation of bile in the liver and impaired excretion of bile into the intestine, causes digestive disorders and the entry of toxic components of bile into the blood and brain. The study of the effect of cholestasis on cholinergic neurons of the cingulate cortex in rats allows us to understand the mechanisms of pathological changes in the brain. The aim was to investigate the effect of cholestasis on cholinergic neurons of cingulate cortex in rats. Material and methods. The study involved 72 outbred white male rats weighing 225±25 g. Subhepatic cholestasis was modeled using the method of L.S. Kizyukevich. The animals of the control group underwent a sham operation. Rats of the control and experimental groups were decapitated on the 2nd, 5th, 10th, 20th, 45th and 90th days. fragments of the cerebral hemispheres were embedded in paraffin and 5 µm thick frontal sections were prepared, stained with antibodies to the choline acetyltransferase (ChAT) protein. Neurons of the cingulate cortex of the rat brain were studied. The number of cholinergic neurons in the preparations was counted, and the relative content of ChAT in their cytoplasm was cytophotometrically estimated. The data were subjected to statistical processing. Results. It was found that, under normal conditions, the number of cholinergic neurons in the parvocellular layer of the cingulate cortex is greater than in the magnopyramidal layer. The content of ChAT in the cytoplasm of the perikarya of neurons in the parvocellular layer decreases 5 and 10 days after cholestasis. With continued cholestasis (on the 10th and 20th days after surgery), the number of cholinergic neurons in the parvocellular layer of the cingulate cortex decreases, indicating their death. The content of ChAT in the cytoplasm of neurons of the magnopyramidal layer decreases only by the 10th day of cholestasis. In this case, the maximum loss of cholinergic neurons is detected on the 45th day. Cholinergic neurons of the parvocellular layer respond faster to cholestasis and the surviving neurons normalize earlier after its disappearance, compared with neurons of the magnopyramidal layer of the cingulate cortex. Conclusion. A decrease in the content of ChAT, indicating a violation of acetylcholine synthesis, and the loss of cholinergic neurons in the cingulate cortex may underlie the cognitive deficit observed in patients with cholestasis.

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