Short-term and complete reversal of NGF effects in rats with lesions of the nucleus basalis magnocellularis.
Rats received bilateral quisqualic acid lesions of the nucleus basalis magnocellularis. Three weeks after lesioning, osmotic minipumps were implanted that released recombinant human nerve growth factor or cytochrome c at a dosage of 5.0 microg rat-1 day-1 through intracerebroventricular cannulas for 7 weeks. One quarter of the rats were sacrificed at the end of the treatment, while the rest of the animals were sacrificed 2, 8, and 12 weeks after termination of NGF/cc treatment. ICV administration of nerve growth factor (NGF) transiently reduced weight gain. NGF maximally increased choline acetyltransferase activity in all cortical regions, the olfactory bulb and the hippocampus between 20% and 56% at the end of the treatment. This increase linearly declined and completely regressed during the 12-week withdrawal period both in regions affected and unaffected by the lesion. Administration of NGF induced a short-lasting hypertrophy of low affinity NGF receptor immunoreactive neurons within the nucleus basalis magnocellularis (NBM), the horizontal limb of the diagonal band of Broca, and the medial septum. In contrast, QUIS-induced NBM lesions permanently reduced ChAT activity most pronounced in the frontal and parietal cortex up to 45%. Furthermore, QUIS induced a permanent loss of p75NGFr-immunoreactive neurons within the NBM and the DB without affecting the MS. These findings suggest that degenerating cholinergic neurons of the NBM and HDB do not spontaneously recover after lesioning and may require continuous neurotrophic support by NGF to ameliorate cholinergic hypofunctioning.
Winkler
J
J
Department of Neurosciences, University of California San Diego, La Jolla, CA 92093-0624, USA.
Power
A E
AE
Ramirez
G A
GA
Thal
L J
LJ
D000818:Animals; D015306:Biogenic Monoamines / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D018690:Excitatory Amino Acid Agonists; D008297:Male; D009410:Nerve Degeneration; D009414:Nerve Growth Factors / Q000494:pharmacology*; D016318:Quisqualic Acid; D051381:Rats; D011916:Rats, Inbred F344; D013377:Substantia Innominata / Q000187:drug effects* / Q000378:metabolism; D013997:Time Factors
D015306:Biogenic Monoamines; D018690:Excitatory Amino Acid Agonists; D009414:Nerve Growth Factors; D016318:Quisqualic Acid; D002795:Choline O-Acetyltransferase