Cholinergic marker deficits induced by lesions of the nucleus basalis of Meynert are attenuated by nerve growth factor in young, but not in aged, F344 rats

Abstract To investigate the efficacy of nerve growth factor (NGF) in promoting recovery from cholinergic damage, young (3–4 month old) and aged (22–23 month old) Fischer 344 rats received NMDA-induced unilateral lesions of the nucleus basalis of Meynert and subcutaneous osmotic pumps (2-week duration) connected to permanently implanted cannulas directed at the lateral ventricle ipsilateral to the lesion. Pumps were filled with either artificial CSF/rat serum albumin (the vehicle) or 5.0 μg of angiotensin-free, β-NGF. Fourteen days after surgery, all subjects were sacrificed and their brains regionally dissected (frontal and occipital cortices, and dorsal and ventral hippocampi) and assayed for choline acetyltransferase (CAT) and acetylcholinesterase (AChE). Results indicated that the lesion decreased CAT and AChE levels within the frontal cortex of both young (29.8% and 39.4% depletion, respectively) and aged (30.5% and 34.8% depletion, respectively) animals. Only in young animals did NGF reduce these lesion-induced CAT (by 34.2%) and AChE deficits (by 65.5%). In fact, NGF exacerbated frontal cortical CAT depletions in aged animals in that percent depletion was 11.3% more following treatment (30.5% vs. 41.8% depletion in Aged/CSF and Aged/NGF groups, respectively). Lower CAT and AChE levels were found in the striatum of aged animals, an effect not reversed by NGF treatment. In contrast, NGF young animals enhanced striatal CAT activity on the non-lesioned side by 22.2%. Although NGF has previously been shown to enhance the functional and structural status of cholinergic cells in aged animals, the present data suggest that such an effect may not apply to aged, cholinergically lesioned neurons or that treatment conditions (e.g. dose, duration of treatment, etc.), which are adequate for promoting recovery in young adult rats, do not apply fully to aged rats.