Llorente, A. , Moreno, M. , Manuel, I. , Giralt, M. T. & Rodríguez , R.
Facultad de Medicina. UPV/EHU
The cholinergic basal forebrain, which innervates cortical, hippocampal and amygdaloid areas, controls learning and memory processes and is damaged in Alzheimer´s disease. The present study analyzed learning and memory after the selective basal forebrain lesion with 192IgG-saporin (SAP). A significant decrease was observed in cholinergic neuron density (P75NTR-ir) in SAP treated rats (-82,7% vs aCSF, p<0,001). We found that cognitive impairment and reduction in P75NTR-ir correlated with each other (r2=0,51, p<0,05). Similar results were observed with decreasing AChE staining in cortical areas (entorhinal: r2=0,55, p<0,01), hippocampus (CA3: r2=0,49, p<0,01) and amygdala (anterior: r2=0,43, p<0,01). We also found a high CB1-ir in basal forebrain of lesioned rats. [35S]GTP-GammaS autoradiography revealed increased CB1 receptor activity stimulated by WIN55,212-2 (10 uM) in lateral olfactory tract (data expressed in % stimulation over basal; CSF vs SAP; 55 ± 11% vs 128 ± 13%, p<0.05) and in entorhinal cortex (156 ± 17% vs 277 ± 30%, p<0.01), but decreased in dentate gyrus (229 ± 32% vs 139 ± 19%, p<0.05) and in medial amygdala (116 ± 20% vs 50 ± 7%, p<0.05). Lysophosphatidic acid (LPA) (10 uM) stimulation showed an increase in the internal capsule (60 ± 10% vs 137 ± 19%, p<0.01). The modulation of CB1 and LPA1 receptor activity in response to the cholinergic impairment may indicate a neuroprotective action in basal forebrain.