Functional and Morphological Changes in the Pyramidal Layer of the Hippocampus in Rats with Encephalopathy Induced by Prolonged Exposure to Gravitational Overloading

Tyurenkov, I. N.; Смирнов, А. В.; Медников, Д. С.; Шмидт, М В; Ekova, Maria; Куркин, Д. В.; Бакулин, Д. А.; Волотова, Е. В.

doi:10.1007/s11055-020-00923-0

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“…According to WHO estimates, depression is one of the leading mental illnesses. One of the most sensitive brain structures to stress is the hippocampus [2,3], which is a target for stress hormones, neurotransmitters and cytokines and is involved in the formation of a stress reaction. The hippocampus functions as a heterogeneous structure with separate dorsal and ventral sections [2].…”

Section: Introductionmentioning

confidence: 99%

“…One of the most sensitive brain structures to stress is the hippocampus [2,3], which is a target for stress hormones, neurotransmitters and cytokines and is involved in the formation of a stress reaction. The hippocampus functions as a heterogeneous structure with separate dorsal and ventral sections [2]. The dorsal hippocampus (DH) receives afferent connections from the entorhinal, archicortex and anterior cerebral cortex, whereas the ventral hippocampus is associated with subcortical structures, including the amygdala complex and parahippocampal regions, the hypothalamus, septum, ventral striatum and olfactory re-gions.…”

Section: Introductionmentioning

confidence: 99%

“…It is believed that damage to the hippocampal neurons may be associated with the excitotoxic effect of high concentrations of glutamate, which occurs through NMDA receptors and causes the release of NO [2]. The formation of NO in the brain occurs with participation of three different isoforms of NO synthases: neuronal (nNOS), endothelial (eNOS), inducible (iNOS) [6].…”

Section: Introductionmentioning

confidence: 99%

“…In addition, NO by the principle of feedback homeostatic regulation causes a decrease in activity of serine racemase (SR) (an enzyme localized not only in astrocytes, but also in neurons and participating in the racemization reaction of D-serine), which leads to a decrease in NMDA-dependent neurotransmission. Excessive activation of oxidative stress leads to inactivation of SR, which affects the synthesis of D-serine in the hippocampal neurons and the dynamics of changes in the neural network underlying memory impairment [2]. It was shown that various types of stress exposure or excessive exposure to glucocorticoids in the hippocampus of rodents and primates causes a decrease in the number and density of neurons in atrophy of dendrites, leads to a decrease in synaptophysin expression and impaired synaptic plasticity mechanisms, which also leads to memory loss and reduces learning ability [7].…”

Section: Introductionmentioning

confidence: 99%

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Morphofunctional changes in ventral and dorsal hippocampus in adult rats after chronic mild stress: a preclinical experimental study

Tyurenkov,

Smirnov,

Ekova

et al. 2024

Kuban. nauсh. med. vestnik

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Background. Stressful influences, depending on their severity and duration, can cause the development of pathological conditions. Repeated episodes of stress cause functional and structural changes in the central nervous system and can cause the development of depressive conditions. Depression is one of the leading mental illnesses. One of the most stress-sensitive brain structures is the hippocampus. Objective. To study is to evaluate structural changes in the hippocampus, which is considered as a heterogeneous structure with separate dorsal and ventral regions, to evaluate the expression of inducible nitric oxide synthase, endothelial nitric oxide synthase, serine racemase, synaptophysin in a mild stress model.Methods. A study of the effects of mild stress was carried out on 16 adult male Wistar rats (age 12 months, body weight 350–400 g). After acclimatization, the rats were divided into two equal groups (n = 8): intact (control) and stressed. When keeping animals, modeling and removing them from the experiment, we were guided by the Regulations for Carrying Out Work Using Laboratory Animals and the Declaration of Helsinki. Experimental modeling of depression in animals was induced by mild stress exposure for 7 days (30 minutes daily). Euthanasia was performed in a CO2 incubator. The brain was fixed in neutral buffered 10% formalin. Paraffin sections were made in the frontal plane, stained with hematoxylin and eosin, thionin using the Nissl method and examined at a level from –2.40 to –3.96 mm relative to bregma using an Axio Lab A1 microscope (Carl Zeiss Microscopy GmbH, Germany). Photo documentation was carried out with an AxioCam 105 color camera (Carl Zeiss Microscopy GmbH, Germany). Using the Image Analysis module of the ZEN 1.1.2.0 program (Carl Zeiss Microscopy GmbH, Germany) in the pyramidal layer of the hippocampus. Statistical analysis was performed with Microsoft Office Excel 2016 (Microsoft, USA) and Prism 6 (GraphPad Software Inc., USA). Comparisons of two conditions were made by nonparametric Mann-Whitney-U test to avoid a statistical bias of unequal data distribution. The level of significance was set at p < 0.05. The summarized data were presented as a as mean ± standard error of mean.Results. Functional research methods and assessment of pathological changes in hippocampal neurons are presented. An increase in the relative number of wrinkled hyperchromatic pyramidal neurons in the dorsal cornu ammonis field 3 in stressed rats was noted by 23.6% (p < 0.05) compared to the control. There was an increase in the relative number of inducible nitric oxide synthase-immunopositive neurons in the dorsal cornu ammonis field 3 by 40% ( p < 0.05) and the relative area of inducible nitric oxide synthase-immunoreactive material by 35% (p < 0.05) in the pyramidal layer of cornu ammonis field 3 in stressed rats. A decrease in the relative area of synaptophysin-immunopositive material in stressed rats was found in the ventral cornu ammonis field 3 compared to the control group by 16.8% (p < 0.05); decrease in the relative area of serine racemase-immunopositive material in dorsal cornu ammonis field 3 by 4.3% (p < 0.05) and ventral cornu ammonis field 3 by 7.8% (p < 0.05).Conclusion. The results of the study demonstrate that mild stress is an adequate model of depression in rats. In animals exposed to mild stress, pronounced morphological signs of damage to hippocampal neurons were revealed; motor and indicative exploratory activity decreases. Differences were found in morphofunctional changes in the dorsal and ventral parts of the hippocampus under the influence of mild stress. In cornu ammonis field 3 of the dorsal hippocampus, in contrast to the ventral section, more pronounced signs of damage to pyramidal layer neurons were observed. The increase in the relative number of inducible nitric oxide synthase-immunopositive neurons and the relative area of inducible nitric oxide synthase-immunoreactive material in the cornu ammonis field 3 pyramidal layer in stressed rats indicates an increase in nitric oxide production and the participation of nitrooxide-dependent free radical mechanisms of damage to hippocampal neurons. The decrease in the relative area of synaptophysin-immunoreactive material in stressed rats may contribute to changes in synaptic plasticity. A decrease in the relative area of serine racemase-immunoreactive material in the dorsal and ventral parts of cornu ammonis field 3 is considered to be a sign of a possible decrease in N-methyl-D-aspartate-dependent neurotransmission in the hippocampus under stress.

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Section: Introductionmentioning

confidence: 99%