RESUMEN
Alpha lipoic acid (LA) is a sulfhydryl compound, used as dietary supplement and to treat a variety of conditions associated to oxidative stress. Glial cells are key modulators of neuroprotection. We show here that LA modulates specific glial parameters in C6 astrocyte cell line, such as glutamate uptake, glutamine synthetase (GS) activity and glutathione content, commonly associated with the protective role of glial cells. LA (10 and 50µM) after 24h of treatment significantly decreased the formation of reactive oxygen species (ROS) and nitric oxide (NO) levels, and increased glutamate uptake (up to 20%), GS activity (25%) and GSH content (up to 40%). LA increase glutamate uptake probably by decreasing oxidizing conditions and/or by mechanism dependent of protein kinase C (PKC). In contrast, high concentrations of LA (1000µM) decreased these glial functions. Moreover, this concentration increased ROS production and NO levels. In summary, these findings show that low doses of LA were able to modulate glial functions and it appears to have remarkable therapeutic potential in neurological diseases involving oxidative stress by improving glutamatergic metabolism.
Asunto(s)
Astrocitos/efectos de los fármacos , Glutamato-Amoníaco Ligasa/metabolismo , Ácido Glutámico/metabolismo , Glutatión/metabolismo , Ácido Tióctico/farmacología , Animales , Astrocitos/metabolismo , Línea Celular , Óxido Nítrico/metabolismo , Estrés Oxidativo/efectos de los fármacos , Ratas , Especies Reactivas de Oxígeno/metabolismoRESUMEN
Caloric restriction (CR) has been shown to either decrease or prevent the progression of several age-related pathologies. In previous work, we demonstrated that CR modulates astrocyte functions, suggesting that CR may exert neuroglial modulation. Here, we investigated the effects of CR on hippocampal (Hc) and cortical (Cx) oxidative stress parameters of male Wistar rats. Our results showed that CR-fed rats had 17% less body weight gain after 12 weeks of treatment. CR improved locomotion performance, increased glutathione levels and decreased glutathione peroxidase activity and the production of reactive oxygen species. However, no changes were observed in lipid peroxidation, nitric oxide content and catalase activity. Single cell gel electrophoresis assay (comet assay) revealed a reduction in the extent of basal DNA damage upon CR. Our data suggest that dietary CR could induce both hippocampal and cortical modulation resulting in metabolic changes and as a consequence, significant improvement of cellular defense-associated parameters.
Asunto(s)
Restricción Calórica , Corteza Cerebral/metabolismo , Animales , Conducta Animal , Ensayo Cometa , Daño del ADN , Masculino , Actividad Motora/fisiología , Oxidación-Reducción , Ratas , Ratas Wistar , Especies Reactivas de Oxígeno/metabolismoRESUMEN
Recent studies indicate that caloric restriction (CR) protects the central nervous system from several pathological conditions. The impairment of astroglial cell function, including glutamate uptake, glutamine synthetase (GS) activity and S100B secretion, may contribute to the progression of neurological disorders. The present study aimed to evaluate hippocampal astrocytic changes in response to CR diet, measuring astroglial parameters, such as glutamate uptake, GS activity and the immunocontent of GFAP and S100B. Blood biochemical parameters were also analyzed. Rats (60-day old) were fed ad libitum or on CR diets for 12 weeks. CR-fed rats showed approximately 16% less body weight gain than control rats. The CR diet was able to induce a significant increase in glutamate uptake (23%) and in GS activity (26%). There were no statistically significant differences in the immunocontent of either GFAP or S100B. In summary, the present study indicates that CR also modulates astrocyte functions by increasing glutamate uptake and GS activity, suggesting that CR might exert its neuroprotective effects against brain illness by modulation of astrocytic functions.
Asunto(s)
Restricción Calórica , Glutamato-Amoníaco Ligasa/metabolismo , Ácido Glutámico/metabolismo , Hipocampo/metabolismo , Animales , Astrocitos/metabolismo , Peso Corporal , Proteína Ácida Fibrilar de la Glía/biosíntesis , Masculino , Factores de Crecimiento Nervioso/biosíntesis , Factores de Crecimiento Nervioso/sangre , Ratas , Ratas Wistar , Subunidad beta de la Proteína de Unión al Calcio S100 , Proteínas S100/biosíntesis , Proteínas S100/sangre , Regulación hacia Arriba , Urea/sangreRESUMEN
Risperidone has demonstrated therapeutic advantages over conventional neuroleptics and offers a valuable emerging option for the treatment of social behavior associated with autistic disorder. Considering the putative involvement of astroglial cells in neuropsychiatric disorders, we investigated the effect of risperidone on parameters of astrocyte activity - glutamate uptake, glutamine synthetase (GS) activity and glutathione (GSH) levels. Risperidone was able to induce a significantly increase on glutamate uptake (32%); GS activity (15%); GSH levels (58%). These findings imply the perspectives for further investigations directed on astrocytes from different brain areas. Our present results suggest that risperidone might exert its neuroprotective effects against brain illness at least partially via modulation of astrocyte functions.