[The role of mercury and arsenic in the etiology and pathogenesis of Parkinson's and Alzheimer's diseases]. / Rol' rtuti i mysh'yaka v etiologii i patogeneze boleznei Parkinsona i Al'tsgeimera.

A critical review of literature data on the toxic effects of mercury and arsenic on the human brain and their relationship with the etiology and pathogenesis of neurodegenerative diseases such as Parkinson's and Alzheimer's diseases is presented. In the first case, the toxic effect of mercury and arsenic on the brain stimulates oxidative stress, which leads to the formation of free oxygen species and a decrease in the antioxidant defense of neurons. In the second case, the harmful effect of mercury changes the structure and properties of ß-amyloid, and the toxic effect of arsenic contributes to its accumulation. In the pathogenesis of the diseases under consideration, particular importance is attached to the reaction of astrocytes that initiate neuroinflammation, which is also characteristic of mercury and arsenic intoxication. Considering that the symptoms recorded during intoxication with mercury and arsenic are in many respects similar to those of Parkinson's and Alzheimer's diseases, and their pathogenetic mechanisms (oxidative stress and neuroinflammation) coincide, then the toxic effects of mercury and arsenic in neurodegenerative diseases analyzed in this review can be characterized as the influence of the most significant risk factors.

[Morphochemical study of alpha-synuclein, iron and iron-containing proteins in the substantia nigra of the brain in Parkinson's disease]. / Morfokhimicheskoe issledovanie al'fa-sinukleina, zheleza i zhelezosoderzhashchikh belkov v chernom veshchestve golovnogo mozga pri bolezni Parkinsona.

OBJECTIVE: To study, using a complex morphochemical approach, the localization of alpha-synuclein, iron compounds and iron-containing proteins in the structures of the substantia nigra of the brain in Parkinson's disease (PD). MATERIAL AND METHODS: Histochemistry and immunohistochemistry methods have been used to study the localization of pathological alpha-synuclein (α-Syn-p129), iron compounds and iron-containing proteins - transferrin receptor and ferritin in neurons and neuroglia in the substantia nigra of the brain of deceased PD patients and persons with no neurological symptoms detected during life (control). RESULTS: In the substantia nigra of PD patients, in comparison with the control, a stable accumulation of pathological alpha-synuclein (α-Syn-p129) in the bodies and processes of neurons was found, and in the neuroglia and neuropil - the accumulation of iron (II) and ferritin heavy chain, the reaction of microglia to protein CD68 was moderately elevated. The transmembrane protein CD71 was detected equally in the brains of PD patients and in controls. CONCLUSION: Synaptic protein alpha-synuclein in PD turns into a pathological metabolite that accumulates in the structures of substantia nigra, and probably disrupts the conduction of nervous excitation. Excessive accumulation of the ferritin heavy chain in neuroglia can increase the concentration of reactive forms of iron and increase neurotoxicity. The uniform distribution of the transmembrane glycoprotein CD71 in the of substantia nigra structures both in the control and in PD patients indicates the preservation of non-heme iron transport during the neurodegenerative process.

[The role of aluminum and lead in the development of Alzheimer's and Parkinson's diseases]. / Rol' alyuminiya i svintsa v razvitii boleznei Al'tsgeimera i Parkinsona.

The article summarizes the data available in the literature on the toxic effects of aluminum and lead on the human brain and assesses the relationship of these effects to the etiopathogenesis of the most common neurodegenerative diseases, such as Alzheimer's and Parkinson's diseases. The accumulation of ions of these metals in the brain structures leads to chronic intoxication that is manifested by the morphological signs that are typical for Alzheimer's disease, such as deposits of ß-amyloid and τ-protein mainly in the frontal and temporal regions of the cortex, and for Parkinson's disease, such as degeneration of dopamine neurons in the substantia nigra and their accumulation of α-synuclein. The most likely forms of participation of aluminum and lead ions in the mechanisms of neurodegeneration are the replacement of bivalent metal ions necessary for brain functioning, oxidative stress initiation, epigenetic modifications of histones, and increased expression of noncoding ribonucleic acids.

[Changes in iron content in brain structures during aging and associated neurodegenerative diseases]. / Izmenenie soderzhaniya zheleza v strukturakh golovnogo mozga pri starenii i assotsiirovannykh s nim neirodegenerativnykh zabolevaniyakh.

The literature data on changes in the content of iron and its metabolites in brain structures during aging and neurodegenerative diseases (Parkinson's disease - PD and Alzheimer's disease - AD) are analyzed. It was revealed that with aging, the iron content in nigrostriatal formations of brain changes: the level of non-heme iron and ferritin increases and neuromelanin also accumulates in neurons of black substance. The accumulation of neuromelanin in combination with increase in ferritin content can be considered as a morphochemical sign of neuroprotective effect of nervous tissue during aging. The iron level in PD and AD compared with that during physiological aging continues to increase, and the ability of chelating agents to bind iron decreases (ferritin in neuroglia cells and neuromelanin in neurons), which activates the mechanisms of cell destruction. As a result, in PD, the aggregation of α-synuclein is disrupted, which leads to the formation of Levi bodies, and in AD, the amyloid beta precursor protein (APP) undergoes proteolysis and this leads to the formation of amyloid plaques, which triggers subsequent neurodegenerative changes, including the death of neurons.

[Clinical and morphological analysis of a caseof Parkinson's disease]. / Kliniko-morfologicheskii analiz sluchaia bolezni Parkinsona.

Parkinson's disease (PD) is a neurodegenerative disease that belongs to a group of cerebral proteinopathies. The main pathomorphological signs of PD are neuronal degeneration in the midbrain substantia nigra and detection of pathological forms of the synaptic protein α-synuclein in the nigral neurons. At the same time, the pathological forms of α-synuclein in this disease have been recently shown to accumulate in the cells of not only the central, but also peripheral autonomic nervous system. The paper provides a clinical and morphological description of a PD case in a 70-year-old patient, which demonstrates that there are typical α-synuclein-positive inclusions in the brain regions (substantia nigra, caudate nucleus, and frontal cortex), salivary glands and colon. The systemic nature of α-synucleinopathy in PD is important in both clarifying the pathogenesis of the disease and elaborating new approaches to its diagnosis and, in the future, to targeted therapy.

[Lewy bodies in Parkinson's disease: histological, immunohistochemical, and interferometric examinations]. / Tel'tsa Levi pri bolezni Parkinsona (gistologicheskoe, immunogistokhimicheskoe i interferometricheskoe issledovanie).

OBJECTIVE: To quantify the morphochemical characteristics of Lewy bodies detected in the substantia nigra in patients with Parkinson's disease (PD). MATERIAL AND METHODS: The investigators studied the localization of alpha-synuclein (α-Syn) and the distribution of neurofilament protein and synaptophysin by immunohistochemical assas and compared with the results of interferometry and computer-assisted morphometry of Lewy bodies in the autopsy specimens of the substantia nigra from PD patients. RESULTS: Three groups of synuclein-positive aggregates differing in shape were identified. Mature Lewy bodies had a rounded shape, a concentric structure, a poorly stained core, and, as compared with neuropil, a high phase difference value. Comparison of the localization of α-Syn, neurofilaments, and synaptophysin showed that immunostaining of neurofilaments in the peripheral layer of Lewy bodies was shifted closer to the nucleus and the localization of synaptophysin and α-Syn coincided. CONCLUSION: Synuclein-positive protein aggregates showed heterogeneity in structure, shape, and protein composition in PD. The localization of neurofilament protein and synaptophysin in Lewy bodies attests that the cytoskeleton and neuronal synaptic vesicle trafficking in the substantia nigra are impaired in BP.

[Neurochemical and morphological changes of microstructures of the compact part of the substantia nigra of human brain in aging and Parkinson's disease (literature review).]

For investigation of pathogenetic patterns of Parkinson's disease, it is important to adequately assess the mechanisms of age-related involution and morphological changes that are formed in the brain during this process. Clinical symptoms, detected in Parkinson's disease (rigidity, hypokinesia, tremor), indicate the involvement in the pathological process of nigrostriate brain formations due to the death of dopamine neurons in the compact part of the substantia nigra. At the same time, the loss of these neurons, as well as the change in the number of neuroglia cells in the substantia nigra of the brain, are detected not only in Parkinson's disease, but also in physiological aging. This review presents and compares data on the morphological changes in the compact part of the substantia nigra of the human brain in physiological aging and Parkinson's disease.

[Morphochemical changes in the substantia nigra cellular structures in Parkinson's disease]. / Morfokhimicheskie izmeneniia kletochnykh struktur chernogo veshchestva golovnogo mozga pri bolezni Parkinsona.

AIM: to clarify the features of morphochemical changes in the substantia nigra cellular structures in Parkinson's disease. MATERIAL AND METHODS: The structural characteristics of the substantia nigra were studied microscopically and quantified using computer morphometric methods at brain autopsies of individuals with Parkinson's disease who had died from intercurrent diseases and those who had no evidence of neurological disorders in their history (a control group). RESULTS: This investigation could clarify the features of morphochemical changes in both the neural network structures and the glial populations of the substantia nigra in Parkinson's disease. The number of neurons containing tyrosine hydroxylase (a marker of dopamine neurons) in the compact part of the substantia nigra (a ventral region) was smaller and the density distribution of Lewy bodies was higher in the patients with Parkinson's disease than in the control group. The accumulation of iron (II) compounds in the cellular elements and neuropile and the increased expression of glial fibrillary acidic protein in Parkinson's disease were more pronounced than those in the controls. CONCLUSION: Postmortem diagnosis in Parkinson's disease should be based on a full description of a set of neuronal and glial morphochemical and structural changes in the substantia nigra rather than on the identification of cellular markers for the neurodegenerative process.

[Morphological parameters of the heterogeneity of the substantia nigra in elderly men and women].

OBJECTIVE: to define the quantitative characteristics of cell structures in the substantia nigra pars compacta of neurologically healthy elderly people (men and women). MATERIAL AND METHODS: Autopsy brain materials from neurologically healthy men and women who had died from intercurrent diseases at the age of 72 to 87 years were examined for quantitative characteristics of the substantia nigra pars compacta, by applying computed morphometric methods. RESULTS: In the elderly people (men and women), the compactness of arrangement of neurons, including those containing tyrosine hydroxylase (a marker of dopamine neurons), was much higher and the glial index was lower in the ventral area of the substantia nigra pars compacta than in the dorsal area. Comparing the structures in the substantia nigra pars compacta showed that the neurons were larger in the dorsal area and the variability of the compactness of their arrangement and the glial index were higher in the women than in the men. CONCLUSION: In the elderly people, the cell structures in the substantia nigra pars compacta are typified by high morphometric heterogeneity.