The specificity of iNOS expression indicators in the basal magnocellular nucleus of rats under early pathogenetic correction in experimental neurodestruction
DOI:
https://doi.org/10.14739/2310-1210.2024.5.309732Keywords:
neuroprotection, nitric oxide synthase, nitrosative stress, neurodegeneration, brain, neurons, cognitive function disordersAbstract
Aim. To characterize iNOS expression indicators in the basal magnocellular nucleus of rats during early pathogenetic correction of neurodegeneration induced by intracerebroventricular colchicine administration.
Materials and methods. The study was conducted using 50 male Wistar rats aged 10–11 months, which were divided into 5 experimental groups (n = 10). The control animals (group 1) were administered a 0.9 % NaCl solution intracerebroventricularly, while the other experimental group rats (groups 2–5) received a colchicine solution in the same manner. The following day, the animals from groups 3–5 were initiated early pathogenetic correction with citicoline (group 3), thiocetam (group 4), and HSF-1 (group 5) lasting 14 days. All the experimental animals (groups 1–5) were then euthanized with sodium thiopental, and their brains were extracted for histochemical, immunofluorescent, and biochemical examinations.
Results. The study has demonstrated that intracerebroventricular administration of colchicine to rats was accompanied by morphological signs of neurodegeneration in the basal magnocellular nucleus and characterized by a significantly smaller area of chromaffin substance in the neurons of this structure by 39 % as compared to the control animals. At the same time, early pathogenetic correction of colchicine-induced neurodegeneration was associated with significantly larger values of Nissl substance area of the basal magnocellular nucleus neurons compared to the corresponding values in animals that did not receive the correction. Additionally, the nitrite level in the brain homogenates of rats administered colchicine without correction (group 2) exceeded the control (group 1) by almost 7 times, while the indicators in experimental groups 3, 4, and 5 exceeded it by 3.5, 2.9, and 3.8 times, respectively. However, no statistical differences were found between the control group and the correction groups in terms of nitrite content. Evaluating the expression of iNOS (the area of immunopositive cells and corrected total cell fluorescence, CTCF) in the basal magnocellular nucleus of the experimental rats it has been shown that the area was most affected in group 5 (HSF-1 correction), exceeding the control parameter by 18.9 %, group 3 (citicoline correction) by 14.7 %, and group 4 (thiocetam correction) by 17.1 %, with no statistical differences compared to group 2 (colchicine administration without correction). Meanwhile, the CTCF of iNOS+-cells in the basal magnocellular nucleus of the experimental animals was the highest in group 2 significantly exceeding the corresponding parameters in the control and correction groups. No significant differences were found between the control and correction groups in this parameter. Additionally, it is noteworthy that intracerebroventricular administration of colchicine to rats, compared to control animals, was associated with a significant double the number of iNOS+ cells in the basal magnocellular nucleus. However, early pathogenetic correction in groups 3-5 did not significantly affect the number of iNOS+ cells in the studied structure, as this parameter did not statistically differ from group 2, although significantly exceeding the corresponding parameter in the control group (group 1).
Conclusions. Early pathogenetically substantiated correction with citicoline, thiocetam, and HSF-1 in colchicine-induced neurodegeneration in the basal magnocellular nucleus of experimental rats is accompanied by an increase in the area of chromaffin substance compared to rats that received intracerebroventricular colchicine without correction, as well as a reduction in nitrite levels in brain homogenates to the control level (sham-operated animals). In the basal magnocellular nucleus of experimental rats, under the influence of early pathogenetically substantiated correction of experimental neurodegeneration, iNOS expression indicators (area of immunopositive cells and CTCF) vary depending on the neuroprotectant used. The number of iNOS+ cells in the basal magnocellular nucleus of experimental rats in the correction groups does not change compared to the group that received intracerebroventricular colchicine without correction and is statistically higher than the corresponding indicator in the control rats.
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