CHRONIC INTRAVENTRICULAR INFUSION WITH NGF IMPROVES LTP IN OLD COGNITIVELY-IMPAIRED RATS

Aged (21 months) cognitively-impaired male Sprague-Dawley rats receive d intraventricular infusion of nerve growth factor (NGF) or cytochrome C (Cit C) for 14 or 28 days using miniosmotic pumps and were evaluate d either 1 week or 3 months after treatment. Groups of untreated young , aged-impaired and aged non-impaired rats were also evaluated. Under narcose recording and stimulating electrodes were stereotactically imp lanted in the dentate gyrus and the perforant path. The stimulation in tensity was individually adjusted to obtain a half-maximal population spike (P) for test stimuli and a quarter-maximal for tetanization. The amplitude and latency of P and the slope (S) of the field EPSP were d etermined before and at 2, 5, 15, 30 and 60 min after tetanization at 400 Hz. Paired stimuli at 30 ms interval were also applied before and after tetanization. Aged, cognitively impaired rats showed an absent S potentiation and a delayed P potentiation, both in amplitude and late ncy, while non-impaired rats behaved like the young controls. Paired p ulse inhibition showed no difference among groups before or after teta nization suggesting that the impaired potentiation is not due to an in creased retroactive inhibition. NGF treatment ameliorates LTP deficits to levels equivalent to non-impaired rats, while Cit C controls showe d no improvement. No differences appear among NGF treated groups, but evidence suggest that the animals evaluated 3 months after treatment d eveloped a stronger potentiation. (C) 1997 Elsevier Science B.V.