Predpolagaetsya, chto disfunkciya tanicitov mozhet byt' odnim iz zven'ev patogeneza kak bolezni Al'cgejmera, tak i diabeta 2-go tipa. Cel'yu raboty bylo oharakterizovat' morfologicheskie izmeneniya tanicitov pri modelirovanii bolezni Al'cgejmera. Krysam linii Vistar vvodili streptozocin v doze 3 mg/kg v lateral'nye zheludochki mozga dlya modelirovaniya bolezni Al'cgejmera. Ocenivali izmeneniya tanicitov gipotalamusa cherez 2, 4 nedeli, 3 i 6 mesyacev posle vvedeniya toksina. Immunogistohimicheskim metodom vyyavlyali markernye belki tanicitov (vimentin, nestin), astroglii (GFAP, glutaminsintetazy) i nejronov (HuC/D), a takzhe ocenivali proliferaciyu kletok (po belku Ki67) i mitohondrial'nye izmeneniya (mitohondrial'nyj kompleks IV, PGC1a). Vvedenie streptozocina privelo k nakopleniyu β-amiloidnogo peptida v gipotalamuse i uvelicheniyu razmerov zheludochkov (p < 0,001). Streptozocin povrezhdal kak α1/α2, tak i β1-tanicity. Intensivnost' okrashivaniya na vimentin α1/α2 tanicitov snizhalas' k 4-j nedele (p = 0,003), a β1-tanicitov — cherez tri mesyaca (p < 0,001). Tu zhe napravlennost' izmenenij nablyudali i dlya nestina. Snizhalos' chislo Ki67+ yader (p < 0,05) i menyalas' ekspressiya belkov, svyazannyh s mitohondriyami. K 4-j nedele posle vvedeniya toksina plotnost' tanicitov gipotalamusa snizhalas'. Krome togo, vyyavili aktivaciyu astroglii, odnako vyrazhennogo povrezhdeniya kak astrocitov, tak i nejronov do chetyrekh nedel' posle vvedeniya streptozocina ne nablyudali. Vyyavlennaya povyshennaya uyazvimost' tanicitov k dejstviyu streptozocina soglasuetsya s predpolozheniem o roli povrezhdeniya struktur gipotalamusa v razvitii kak lokal'nyh, tak i sistemnyh metabolicheskih narushenij pri modelirovanii bolezni Al'cgejmera.

Localizing lesions in the brain of rodents after administration of neurotoxic 6-hydroxidopamine (6-OHDA) is important for understanding the mechanisms of progression of parkinsonism. The present study provides the results of behavioral tests, immunohistochemistry, and measurements of dopamine (DA) level in different areas of the striatum 25 days after unilateral intranigral injection of 6-OHDA to rats. Neuronal death was observed in the both pars compacta of the substantia nigra and the lateral nucleus of the ventral tegmental area (VTA). Detailed analysis of DA levels showed a 90% decrease in the dorsal striatum and a 73% decrease in the ventral striatum only at the side ipsilateral to toxin injection. The changes discovered in VTA are similar to the results of morphological post mortem studies of Parkinson's disease. Previously described emotional disturbances in rats with 6-OHDA-induced Parkinson's disease may be related to the damage in VTA shown in our study.

Оценка эффективности антиоксидантных (АО) препаратов при введении на поздней стадии экспериментального паркинсонизма в условиях тотальной гибели нейронов черной субстанции (ЧС) и нарушений дофаминергической иннервации стриатума является актуальной проблемой. Целью исследования было оценить эффективность АО карнозина и липоевой кислоты (ЛК) в модели поздней стадии паркинсонизма. Паркинсонизм индуцировали у крыс с помощью унилатерального стереотаксического введения 6-гидроксидофамина (ГДА) в ЧС правого полушария. АО вводили 4 раза, начиная с 14-го дня после введения токсина. Изучали влияние препаратов на поведение, гибель нейронов ЧС и метаболизм медиаторовмоноаминов. Оба препарата снижали развитие неврологической симптоматики и нарушения поведения, вызванные ГДА. Введение ГДА приводило к снижению уровня дофамина (ДА) и его метаболитов в правом стриатуме на 90% (p = 0,01) и гибели более 95% нейронов в ЧС правого полушария (p = 0,01). АО значимо не влияли на количество нейронов в ЧС, но увеличивали содержание метаболитов ДА относительно животных, получавших ГДА, при этом повышение содержания ДА (в 5,8 раз; p = 0,007) наблюдали только у животных, получавших карнозин. Введение ЛК способствовало снижению серотонина на 23% (p = 0,006) и его метаболита 5-гидроксииндолуксусной кислоты (ГИУК) на 36% (p = 0,009). Таким образом, при отсутствии прямого нейропротекторного эффекта было обнаружено симптоматическое действие карнозина и ЛК, что обосновывает возможность их использования в качестве дополнительной терапии болезни Паркинсона.

We assessed changes of olfactory bulbs in rata with 6-hydroxydopamine destruction of the substantia nigra. The expression of marker proteins of immature and differentiated neurons and glia (vimentin, PSA-NCAM, tyrosine hydroxylase, and S100) was analyzed by immunohistochemical and morphometric methods. The number of periglomerular dopamine neurons and astroglia in the olfactory bulbs increased on the side of toxin injection and expression of PSA-NCAM and vimentin increased in the rostral migratory stream. Destruction of the substantia nigra shifted differentiation of neuronal progenitors towards the dopaminergic phenotype and increased their survival in the olfactory bulbs, which can be explained by increased expression of PSA-NCAM.

The late stage of Parkinson’s disease is characterized by massive neuronal loss in the substantia nigra (SN) and degeneration of the dopaminergic innervation in the striatum. There is a need to assess the neuroprotective effect of antioxidants (AO) at this stage of the disease. The aim of our study was to assess the efficacy of two AO, carnosine and lipoic acid (LA), in the rat model of late-stage parkinsonism. The pathology was induced by a unilateral injection of 6-hydroxydopamine (6-OHDA) into the SN of the right brain hemisphere. AO were administered 4 times, starting on day 14 following the injection of the toxin. We investigated the effect of the injected drugs on the behavior of rats, the loss of neurons in the SN and the metabolism of biogenic neurotransmitter amines. Both AO dampened the development of 6-OHDA-induced neurological and behavioral symptoms. 6-OHDA induced a 90% drop ( p = 0.01) in the levels of dopamine (DA) and its metabolites in the right striatum and caused death of over 95% of neurons ( p = 0.01) in the SN of the right hemisphere ( p = 0.01). AO did not have a significant effect on the number of neurons in the SN but caused an increase in the levels of DA metabolites, as compared to their levels in the animals exposed to 6-OHDA. Elevated DA (a 5.8-fold increase, p = 0.007) was observed only in the animals treated with carnosine. LA stimulated a 23% decline in serotonin levels ( p = 0.06) and a 36% increase ( p = 0.009) in its metabolite, 5-hydroxyindolacetic acid (5-HIAA). We conclude that although carnosine and LA did not have a direct neuroprotective effect, they could relieve the symptoms. This suggests that these AO could be used as an adjunctive component to antiparkinsonian therapy. a simultaneous in findings suggest that the tested antioxidants could be in with conventional antiparkinsonian drugs

Background : Obesity is a risk factor for cognitive disorders. However, it is still unknown whether low-calorie diet will improve cognitive function in obese patients. Aim : To evaluate cognitive function and metabolic features in male Sprague-Dawley rats receiving high-fat and low-calorie diets. Materials and methods : The work was carried out on Sprague Dawley male rats (n = 32), which were divided into 2 groups with 16 animals in each group: Control (normal / low-calorie diet) and Obesity (high-fat diet). In 90 days the rats of the Control group were transferred to a low-calorie diet, the rats of the Obesity group continued to receive high-fat diet. To assess motor activity and cognitive functions at the end of the study (180 days), following behavioral tests were conducted: field, beam, elevated plus-maze (EPM) and avoidance reaction. During the study glucose tolerance test were performed: at baseline (GTT 1) and in 30 days (GTT 2). Results : Obesity group rats gained weight significantly faster than the animals (547.69 ± 11.32 g against 442.8 ± 19.8 g at study end, p = 0.0001). GTT 2 showed normal carbohydrate metabolism in group, postprandial hyperglycemia in obesity group. Testing in the open field showed that the rats of the obesity group moved more actively across the installation area than the ones: the total distance covered was 9.352 ± 0.932 m against 6.781 ± 0.951 m, p = 0.046. The results of a tapering beam test showed that the number of hind limb extrusions in obese rats significantly exceeded this parameter in group (33.7 ± 3 vs. 15.7 ± 2.7, p = 0.0001), test time in both groups did not differ. When testing in EPM, there was no significant difference in any of the key test parameters between the groups. However, the number of looking out from the closed arms in animals of the obesity group was significantly higher than in the group (4.19 ± 0.6 vs. 2.30 ± 0.58, p = 0.044). When testing the reproduction of conditional reactions of passive avoidance it was shown that after day 1 of the pain stimulation application the latent period of transition to the dark compartment in the obesity group was significantly higher than that of the group (180.0 ± 0.0 vs. 128 86 ± 21.45, p = 0.008). This indicates a better preservation of the memorial trail compared to the control rats. By the end of the study 30% of animals in the group died. Conclusions : Rats on high-fat diet were more active, less anxious and showed better results in training tests comparing to animals on low-calorie diet. Adherence to low-calorie diet may be harmful for cognitive functions.

Development of new approaches to the treatment of Alzheimersdisease (AD) is an actual problem of modern neurology owingto high prevalence of AD in the population and severe irreversibledisability resulting from this disease. We investigated the effectsof new peptide compounds, -casomorphin-7 and colostrinin,in two complementary AD models in rats (with injectionof -amyloid into the nucleus basalis of Meynert and injectionof streptozocin in the ventricles of the brain). Peptides were injectedintranasally within 10 days after the onset of AD symptomsinduced by neurotoxins. Injection of -casomorphin-7and colostrinin had similar effect on the behavior and cognitivefunction of rats with both amyloid and streptozocin AD model:there was statistically significant increase in locomotor activityand orienting responses, as well as improvement of animalscognitive functions. Colostrinin had stronger positive effect onthe behavior of rats with induced AD, whereas -casomorphin-7had an effect on both sham-operated and model animals, whichis indicative of the general neurotropic potential of this peptide.The proposed experimental approaches improve the capabilitiesof investigation of novel biologically active compounds aimed atprevention and treatment of neurodegenerative diseases.