Abstract
Astrocytes can protect neurons against oxidative stress and excitability-dependent disorders, such as epilepsy. Valeriana officinalis has been used as anticonvulsant and can exert an antioxidant effect, which may underlie its opposing action against the toxic effects of the pesticide rotenone. We investigated the V. officinalis/rotenone interaction in the cortical spreading depression (CSD), a phenomenon that depends upon brain excitability (in vivo model). In addition, we analyzed the protective action of V. officinalis against the cytotoxic effects of rotenone in cultures of rat C6 glioma cells (in vitro model). For the CSD study, Wistar rats received either V. officinalis (250 mg/kg/day via gavage for 15 days; n = 8) or 10 mg/kg/day rotenone via subcutaneous injections for 7 days (n = 7), or they received both substances (n = 5). Two control groups received either saline (vehicle for V. officinalis; n = 8) or 1% Tween-80 aqueous solution (vehicle for rotenone; n = 9). After treatment, CSD was recorded for 4 h. The rotenone- and V. officinalis-treated groups presented, respectively, with lower (2.96 ± 0.14 mm/min), and higher CSD propagation velocity (3.81 ± 0.10 mm/min) when compared with the controls (Tween-80, 3.37 ± 0.06 mm/min and saline, 3.35 ± 0.08 mm/min; p < 0.05). The rotenone plus V. officinalis-treated group displayed a CSD velocity (3.38 ± 0.07 mm/min) that was similar to controls. In line with these results, in vitro experiments on rat glioma C6 cells revealed a protective effect (MTT assay) of V. officinalis against rotenone-induced cytotoxicity. These results suggest the therapeutic potential of V. officinalis for treating neurological diseases involving redox imbalance and astrocyte dysfunction.
Highlights
Astrocytes are intimately involved in diverse neuronal functions, such as modulating synaptic activity and plasticity; regulating the extracellular microenvironment by buffering neurotransmitter, ion, and water content, and regulating local blood flow and the delivery of energy substrates (Devinsky et al, 2012)
We demonstrated a novel action of V. officinalis extract on the cortical spreading depression (CSD) phenomenon in vivo, which represents an advancement of the knowledge in this field
The present results constitute the first evidence that systemic administration of V. officinalis and rotenone exert opposite effects on CSD propagation in the rat cortex
Summary
Astrocytes are intimately involved in diverse neuronal functions, such as modulating synaptic activity and plasticity; regulating the extracellular microenvironment by buffering neurotransmitter, ion, and water content, and regulating local blood flow and the delivery of energy substrates (Devinsky et al, 2012). Dysregulation of astrocyte function may cause seizures or promote epileptogenesis (Wetherington et al, 2008; Chan et al, 2019). The combined occurrence of high utilization of energy and impairment of oxidative phosphorylation jeopardizes the cells’ capacity to regulate their energy levels. This can lead to excessive production of reactive oxygen species (ROS), causing neuronal injury. Impaired energy metabolism may play a critical role in the neuronal injury caused by oxidant substance-induced epilepsy (Gupta et al, 2000; Bolson and Steinhäuser, 2018)
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