REVERSAL OF SPATIAL MEMORY IMPAIRMENTS IN AGED RATS BY NERVE GROWTH-FACTOR AND NEUROTROPHIN-3 AND NEUROTROPHIN-4/5 BUT NOT BY BRAIN-DERIVED NEUROTROPHIC FACTOR

Aged rats, displaying impairments in spatial learning and memory associated with marked cellular atrophy of forebrain cholinergic neurons, received intracerebroventricular infusions of one of the four neurotrophins nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin 3 (NT-3), or neurotrophin 4/5 (NT-4/5), or a combination of NGF and BDNF, or vehicle. During the 4-week infusion period rats receiving NGF, NT-3, or NT-4/5 showed improved acquisition and retention of spatial memory. With NGF and NT-3, but not NT-4/5, this was accompanied by a significant reduction in cholinergic neuron atrophy in septum, nucleus basalis, and striatum. BDNF, in contrast, was without effect either alone or in combination with NGF. These results show that memory deficits associated with aging can be re versed by several members of the neurotrophin family and that this effect may be mediated through activation of multiple neurotrophin receptors associated with cholinergic and possibly noncholinergic systems in the brain.