REVERSAL OF AGE-DEPENDENT COGNITIVE IMPAIRMENTS AND CHOLINERGIC NEURON ATROPHY BY NGF-SECRETING NEURAL PROGENITORS GRAFTED TO THE BASAL FOREBRAIN

A highly NGF-secreting cell line was generated by retroviral transduct ion of a conditionally immortalized CNS-derived neural progenitor cell line. After transplantation to the nucleus basalis magnocellularis (N BM), the cells continue to express the NGF transgene for at least 10 w eeks, producing sufficient NGF to reverse cholinergic neuron atrophy i n aged rats and induce cellular hypertrophy in young rats. In cognitiv ely impaired aged rats, transplants of the NGF-secreting cells placed either in the NBM and septum or in only the NBM induced a near-complet e reversal of the spatial learning impairment. This was accompanied by a normalization of the size of the cholinergic neurons in the grafted areas. The results demonstrate that locally increased supply of NGF t o the basal forebrain cholinergic nuclei has a significant impact on c ognitive function and support the usefulness of neural progenitor cell s for long-term localized delivery of neurotrophins to the CNS.