Protection in Glutamate-Induced Neurotoxicity by Imidazoline Receptor Agonist Moxonidine

Abstract

In the present study we investigated the effects of mixed imidazoline-1 and α₂-adrenoceptor agonist, moxonidine, in glutamate-induced neurotoxicity in frontal cortical cell cultures of rat pups by dye exclusion test. Also, phosphorylated p38 mitogen activated protein kinases (p-p38 MAPK) levels were determined from rat frontal cortical tissue homogenates by two dimensional gel electrophoresis and semidry western blotting. Glutamate at a concentration of 10⁻⁶ M was found neurotoxic when applied for 16 hr in cell cultures. Dead cell mean scores were 12.8 ± 0.5 for control and 52.3 ± 4.8 for glutamate (p < .001). On the other hand, p-p38 MAPK levels start to increase at a glutamate concentration of 10⁻⁷ M for 20 min application. Moxonidine was found to have an U-shape neuroprotective effect in glutamate-induced neurotoxicity in neuronal cell culture experiments. Even though moxonidine did not induce neurotoxicity alone between the doses of 10⁻⁸ to 10⁻⁴ M concentrations in cell culture series, it caused the reduction of glutamate-induced dead cell population 23.07 ± 3.6% in 10⁻⁶ M and 26.7 ± 2.1% in 10⁻⁵ M concentrations (p <.001 for both, in respect to control values). The protective effect of moxonidine was confirmed in 10⁻⁸ and 10⁻⁷ M, but not in higher concentrations in glutamate neurotoxicity in gel electrophoresis and western blotting of p-p38 MAPK levels. In addition to other studies that revealed an antihypertensive feature of moxonidine, we demonstrated a possible partial neuroprotective role in lower doses for it in glutamate-mediated neurotoxicity model.

Keywords:

• glutamate
• imidazoline receptors
• moxonidine
• neurotoxicity