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Introduction. As Parkinson's disease (PD) develops, a number of non-motor signs precede motor symptoms, including gastrointestinal tract dysfunction. Modelling early-stage PD to comprehensively assess the pattern of morphofunctional changes in the gastrointestinal tract is important in order to develop methods of early disease diagnosis and more effective treatment of autonomic disturbances that are typical in PD, and to increase the patients' quality of life. Study aim to offer a model of early-stage PD through long-term oral administration of small doses of the neurotoxin rotenone to rats, and to study the functional and immunohistochemical changes in the gastrointestinal tract of the experimental animals, as well as changes in the substantia nigra. Materials and methods. The experiment was conducted in male Wistar rats aged 3.03.5 months. The study group rats (n = 10) were given rotenone orally at a dose of 5 mg/kg, as a suspension in a 4% carboxymethyl cellulose solution, every second day for 7 months. The control group rats (n = 10) received only the 4% carboxymethyl cellulose solution. The animals' mobility was assessed at the start and end of the experiment using the open field and narrowing beam-walking test. Gastrointestinal motility was assessed by measuring the passage of dye from the pylorus in a caudal direction along the small intestine. The rats were decapitated and immunohistochemistry was used to assess the density of dopamine neurons in the substantia nigra, nerve fibres, and glia in the Auerbach's plexus of the small intestine, and the location of the total and phosphorylated alpha-synuclein in the enteric nervous system. Results. Rats in the study group had a statistically significant reduction in the number of dopamine neurons in the substantia nigra. Auerbach's plexus of the small intestine contained significantly less nerve fibres and glia, while fluorescence intensity for alpha-synuclein was increased. Phosphorylated alpha-synuclein was identified in the cholinergic and adrenergic fibres of Auerbach's plexus. Experimental animals had a statistically significant reduction in the gastric emptying rate and small intestine motility compared to the control group. Conclusion. The presented model of early-stage PD enables the physiological and immunohistochemical symptoms of gastrointestinal dysfunction, similar to that of patients with PD, to be replicated. They are based on intestinal denervation changes and accumulation of abnormal forms of alpha-synuclein in the enteric nervous system.

A 3-acetyl analogue of 5-hydroxyindole was synthesised and evaluated for its effects on rat C6 glioma cell functions. It was found that 3-acetyl-5-hydroxy-2-methylindole at 10 μmol/L led to a sharp reduction of mitochondrial membrane potential, induction of autophagy and decrease of proliferation of C6 glioma cells. The compound’s effect was comparable to that of rotenone, an inhibitor of cell respiration.

Copyright of National Academy of Sciences of Armenia Reports / Doklady Nacionalnaâ Akademiâ Nauk Armenii is the property of National Academy of Sciences of the Republic of Armenia and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

This paper addresses spatial aspects of reactive astrogliosis in the substantia nigra pars compacta (SNc) of the rat brain observed 40 and 70 days after the intracerebral 12 µg rotenone infusion. The infusion was shown to cause a marked increase in astrocyte density at both analyzed time points. Minimal spanning tree (MST) analysis was applied to analyze spatial patterns formed by nigral astrocytes. Spatial clusters of these cells, identified as disjoint MST subgraphs, were more numerous in the infused SNc tissue as compared with the control one. Size and density of clusters were significantly different between the infused and control areas 40 and 70 days after the infusion. In conclusion, the data suggests that rotenone-related astrogliosis in the substantia nigra includes changes in spatial patterns of astrocytes as well as transient spatial clustering of these cells. [ABSTRACT FROM AUTHOR]

Copyright of National Academy of Sciences of Armenia Reports / Doklady Nacionalnaâ Akademiâ Nauk Armenii is the property of National Academy of Sciences of the Republic of Armenia and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The neurotoxins rotenone and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (МPTP) are used for modeling Parkinson's disease in animals (PD). They induce the mitochondrial respiratory chain dysfunction, which leads to the dopaminergic (DA) neuron degeneration. The advantage of the rotenone model consists in ability of rotenone to cause neurodegeneration showing symptoms and molecular biological characteristics similar to those of PD. Isatin (indoldione-2,3) is an endogenous regulator found in tissues and biological fluids of humans and animals. It exhibits a broad range of biological activity mediated by numerous isatin-binding proteins. In this work we have investigated behavioral reactions and profiles of brain isatin-binding proteins of rats with Parkinson's syndrome (PS) in comparison with the corresponding parameters of MPTP-induced Parkinsonism in mice. Systemic injection of rotenone caused severe PS comparable with the effect of MPTP injection. It was accompanied by significant body weight loss, death, oligokinesia, muscular rigidity, and postural instability of animals. In spite of the same pathogenic basis of PS caused by rotenone and MPTP, the molecular mechanisms of their action differ. In the case of rotenone-induced PS, the pool of isatin-binding proteins common of the control rats and the rats with PS (146) significantly exceeded the pool of the common proteins of control mice and mice with PS induced by MPTP, whether right after neurotoxin injection (27), or (all the more) in a week after the MPTP injection (14). The comparison of isatin-binding proteins specific of the animals with MPTP-induced PS and with the rotenone-induced PS (as compared with the control animals) revealed total absence of proteins common of these two models of PD. It is to be noted that both neurotoxins particularly affected the proteins participating in the signal transmission and enzyme activity regulation. The changes of the profile of isatin-binding proteins in response to the injection of rotenone suggest that the neuroprotector isatin could also influence positively in the case of the rotenone model of PD.

Aim: To assess the efficacy of transcranial electrostimulation TES for treatmnet of anxiety-like behavior and motor disorders in rats with rotenone-induced parkinsonism., Material and Methods: The study was performed on 30 mature male-rats. Animals were divided into following groups: control, intact rats (group 1); rats with an experimental model of parkinsonism without treatment (group 2); rats with an experimental model of parkinsonism, which had 7 sessions of TES-therapy (group 3), the number of rats in each group was 10. The parkinsonism model was achieved by daily rotenone administration for 28 days. Parkinsonism's markers were assessed using 3-point scale; anxiety-like behavior and motor activity were assessed in the open-field test. TES was performed using TRANSAIR-stimulator for 7 days. Substantia nigra slices were stained with hematoxylin and Lillie's staining for neuromelanin., Results: The rats of group 3 show less neurological deficits, less anxiety-like behavior and less neurodegeneration in the substantia nigra. There are a decrease in individual total scores of motor disorders by 50%, a decrease in the level of anxiety-like behavior or the absence of its increase in the open-field test., Conclusion: TES-therapy may be used as an additional non-pharmacological treatment of motor and related non-motor damage in Parkinson's disease.

Rats with experimental Parkinson's syndrome induced by seven-day intraperitoneal administration of rotenone at a dose of 2.75 mg/kg have an increased activity of prolylendopeptidase (EC 3.4.21.26, PREP) in blood serum and a decreased activity of adenosine deaminase (EC 3.5.4.4, ADA) in serum and in the prefrontal cortex. PREP and ADA activity in other brain structures (in the striatum, hypothalamus and hippocampus) did not change; dipeptidyl peptidase IV activity (EC 3.4.14.5, DPP-4, CD26) also remained constant in serum and in all the brain structures investigated. Afobazole and levodopa, which exhibit antiparkinsonian activity in this model of Parkinson's syndrome, decrease elevated PREP activity in serum and increase reduced ADA activity in the prefrontal cortex of rats with the experimental pathology. Meanwhile, treatment with the study drugs was associated with a decrease of ADA activity in the other brain structures.

Aim: To evaluate the efficacy of the combined use of citicoline (neipilept) and levodopa/carbidopa (nakom) in the rotenone model of Parkinson's disease in rats., Material and Methods: Rotenone was administrated during 14 days in dose 2 mg/kg/day subcutaneously. The duration of treatment was 7 days, intragastrically. Alteration of locomotor behavior components, muscular rigidity in resistance to passive flexion in the ankle joint and signs of extrapyramidal disorders were assessed., Results and Conclusion: Combined therapy led to the decrease in muscle rigidity (the decrease of gibbosity in resistance to passive flexion in the ankle joint). There was a decrease in oligokinesia that emerged in higher vertical and horizontal locomotor activity of experimental animals, decrease in the time of head turning during climbing down the pole and total time of climbing down the pole. The combination of drugs had a more pronounced therapeutic effect on extrapyramidal disorders compared to monotherapy.