Given their anti-inflammatory properties, cannabinoids have been shown to be neuroprotective agents and to reduce excitotoxicity, through the activation of the Cannabinoid receptor type 1 (CB1r). These properties have led to CB1r being proposed as pharmacological targets for the treatment of various neurodegenerative diseases. Amyloid-β 25-35 (Aβ25-35) induces the expression of inducible nitric oxide synthase (iNOS) and increases nitric oxide (NO●) levels. It has been observed that increased NO● concentrations trigger biochemical pathways that contribute to neuronal death and cognitive damage. This study aimed to evaluate the neuroprotective effect of an acute activation of CB1r on spatial memory and its impact on iNOS protein expression, NO● levels, gliosis and the neurodegenerative process induced by the injection of Aβ(25-35) into the CA1 subfield of the hippocampus. ACEA [1 μM/1 μL] and Aβ(25-35) [100 μM/1 μL] and their respective vehicle groups were injected into the CA1 subfield of the hippocampus. The animals were tested for spatial learning and memory in the eight-arm radial maze, with the results revealing that the administration of ACEA plus Aβ(25-35) improves learning and memory processes, in contrast with the Aβ(25-35) group. Moreover, ACEA plus Aβ(25-35) prevented both the increase in iNOS protein and NO● levels and the reactive gliosis induced by Aβ(25-35). Importantly, neurodegeneration was significantly reduced by the administration of ACEA plus Aβ(25-35) in the CA1 subfield of the hippocampus. The data obtained in the present research suggest that the acute early activation of CB1r is crucial for neuroprotection.
Keywords: CB1 receptor; amyloid-β((25–35)); hippocampus; iNOS; neurodegeneration; spatial memory.
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