Immunoregulatory and neuroprotective activity of ovocystatin

INTRODUCTION: Ovocystatin has beneficial properties for cognitive function in young rats and might prevents aging-related cognitive impairment in older animals, as well as reduces memory decline in APP/PS1 mice model. OBJECTIVES: Our study aimed at assessing the impact of ovocystatin on microglia activation and neurogenesis. METHODS: Immunoactivation: Mouse wild type microglia were stimulated with ovocystatin at dose of 100 micrograms/ml. The effect of ovocystatin on nitric oxide production and interleukin 1 beta secretion were determined. Neurogenesis: Primary rat hippocampal neurons of H19-7 cell line was used. The impact of ovocystatin on proliferation, nitric oxide production, and expression of markers of neurogenesis: microtubule-associated protein 2 (MAP2, isoforms A/B and C/D) and Synapsin 1, were determined. RESULTS: It was shown that ovocystatin does not stimulate microglial cells to produce inflammatory mediators. Whereas, no toxic effect of ovocystatin (1-100 ug/ml) on H19-7 cells viability, and dose-dependent down-regulation of proliferation were demonstrated. It was also shown that in primary hippocampal neurons of H19-7 cells incubated with ovocystatin (100 micrograms/ml), the expression level of MAP2 C/D (75kDa) - characteristic form of immature neurons is unchanged. However, the increased expression of MAP2 A/B protein (280 kDa) – characteristic for mature neurons was observed after 6 and 24h incubation with ovocystatin. Relatively to MAP2 A/B, increased expression of synapsin 1 was observed. CONCLUSIONS: The ovocystatin might be a potential activator of molecular mechanisms in primary hippocampal neurons, participating in regulation of neurogenesis. Nevertheless, further studies are needed. DISCLOSURE: No significant relationships.