Administration of clenbuterol improves morphology of cholinergic neurons and cognitive processes in aged rats
A defi cit in the cholinergic system of the basal forebrain (BF) is thought to contribute to the development of cognitive symptoms of dementia. Forebrain cholinergic neurons are highly dependent on nerve growth factor (NGF) for phenotype maintenance. Attempts to prevent age-associated cholinergic vulnerability and deterioration therefore represent a crucial point for pharmacotherapy in the elderly. The pharmacological induction of endogenous NGF synthesis in the brain could be an elegant way to overcome application problems. Therefore, the present experiment was undertaken to determine the infl uence of prolonged pharmacological stimulation of NGF biosynthesis on learning and memory in aged rats. To address these issues we used young (4-month-old) and aged (28-month-old) rats in which we stimulated endogenous NGF biosynthesis by treatment with clenbuterol (β2-adrenergic receptors agonist). The cognitive behavior of the young and aged rats was assessed in the long-lasting “Non-Matching to Position Test”. Our data suggest that in aged rats, clenbuterol positively affects cognitive processes related to formation of associations established in recognition memory and discrimination tasks. In addition, NGF signifi cantly improved morphological parameters of BF cholinergic cells in aged rats. These data suggest that endogenous NGF induction restores the age-related decline of the cholinergic system activity in rats, resulting in improvement of water maze performance in old animals.
- Department of Applied Physiology, Mossakowski Medical Research Centre Polish Academy of Sciences, Warsaw, Poland