Immunohistochemical Analysis of Mitochondrial Dynamics in Different Zones of the Hippocampus during Experimental Modeling of Alzheimer's Disease.

We performed a comparative assessment of the immunohistochemical distribution of markers of mitochondrial fission (Drp-1), mitochondrial fusion (Mfn-2), and mitochondrial biogenesis (PGC-1α) in pyramidal neurons of different zones of the hippocampus in mice with intrahippocampal administration of ß-amyloid peptide 25-35. The most pronounced changes in the dynamics associated with a decrease in the amount of the fission marker and an increase in the amount of the fusion marker were observed in the CA3 field on day 38 after peptide administration. In the CA1 field, a significant decrease in the marker of mitochondrial biogenesis PGC-1α was found on day 38, which can indicate a decrease in the intensity of mitochondrial biogenesis. Early mitochondrial changes can play an important role in the pathogenesis of all types of memory impairment in Alzheimer's disease.

The Neurotoxic Effect of ß-Amyloid Is Accompanied by Changes in the Mitochondrial Dynamics and Autophagy in Neurons and Brain Endothelial Cells in the Experimental Model of Alzheimer's Disease.

A comparative assessment of the expression of the mitochondrial fission marker Drp1 and the autophagy marker LC3 in neurons and endothelial cells in the hippocampus and entorhinal cortex during progression of cognitive deficit was performed in animals with intrahippocampal administration of ß-amyloid. In both brain regions, the expression of Drp1 and LC3 in neuronal and endothelial cells was enhanced. The peak of cognitive impairment corresponded to the maximum expression of Drp1 and LC3 in hippocampal neurons and was preceded by an increase in the number of Drp1+ and LC3+ endothelial cells in this brain region. These data attests to a possible role of aberrant mitochondrial dynamics and autophagy of endothelial cells in the impairment of brain plasticity in the Alzheimer's type neurodegeneration.

[Morphological characteristics of the brain nervous tissue during aging]. / Morfologicheskaya kharakteristika nervnoi tkani golovnogo mozga pri starenii.

OBJECTIVE: Identification of morphological manifestations and evaluation of morphometric parameters of the nervous tissue in various structures of the human brain during aging. MATERIAL AND METHODS: Autopsy material was obtained from patients whose causes of death were not associated with neurological diseases. Three age groups were studied: young (35-45 years old) (n=10); eldery (75-89 years old) (n=20); centenarians (over 90 years old) (n=10). Quantitative analysis of large neurons in the compact part of the substantia nigra, basal ganglia, layer V of the cortex, and the pyramidal layer of the hippocampus was carried out. In addition, the brain mass, the thickness of the cortex of the precentral gyrus were measured, the glial index was calculated, and the morphological signs of age-related involution of the brain tissue and intracerebral vessels were assessed. RESULTS: In senile and centenarians, compared with young people, there was a progressive reduction in large neurons of layer V of the cortex, basal ganglia, the pyramidal layer of the hippocampus and substantia nigra, a decrease in brain mass and thickness of the cortex of the precentral gyrus, as well as an increase in the glial index. Changes in blood vessels characteristic of aging are described. Also, during aging, signs characteristic of neurodegeneration were found. CONCLUSION: The results of the study confirm that such brain structures as the cortex of the precentral gyrus, the hippocampus, the basal ganglia, and the substantia nigra lose large neurons with age, followed by the development of gliosis. The identified morphological changes characteristic of aging are phenomenologically similar to a certain set of morphological changes in neurodegenerative diseases of late age.

[Molecular Mechanisms of Interactions between Mitochondria and the Endoplasmic Reticulum: A New Look at How Important Cell Functions are Supported].

Interactions between the endoplasmic reticulum (ER) and mitochondria have received insufficient attention until recently. However, distorted contacts between the ER and mitochondria were identified as an important factor in the etiopathogenesis of neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis. In view of these new data, the mechanisms of ER-mitochondrial interactions are necessary to study in detail in order to develop new diagnostic and therapeutic approaches to neurodegenerative diseases and to extend basic knowledge of the physiology of the eukaryotic cell. The review focuses on the functions of mitochondria-associated ER membranes (MAMs). Structural elements of the MAM system, their contributions to the vital cell functions (calcium and lipid homeostasis, autophagy, fusion and division of mitochondria, and the regulation of their number), and the role of MAM dysfunctions in the pathogenesis of various neurodegenerative diseases are considered.