Effects of nerve growth factor treatment on rats with lesions of the nucleus basalis magnocellularis produced by ibotenic acid, quisqualic acid, and AMPA.
Rats with bilateral lesions of the nucleus basalis magnocellularis (NBM) produced by ibotenic acid (IBO), quisqualic acid (QUIS), and alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) received either human recombinant nerve growth factor (NGF) (5.0 micrograms/day) or cytochrome c (cc) (0.3 microgram/day) treatment. Spatial memory impairments in the Morris water maze differed for the three toxins in the following order: IBO-cc > AMPA-cc > QUIS-cc. Treatment with NGF resulted in behavioral improvement for only the IBO-lesioned rats. Body weight was not affected by the different lesions before treatment; however, administration of NGF resulted in a decreased rate of body weight gain independent of the excitotoxin used. Reduction in choline acetyltransferase (ChAT) activity differed in the neocortex for the three toxins, whereas the hippocampus was unaffected. The cortical ChAT depletion was greatest for AMPA, intermediate for QUIS, and least for IBO. Restoration of ChAT activity by NGF differed for the three toxins (QUIS-NGF > IBO-NGF > AMPA-NGF), whereas ChAT activity in the hippocampus was increased equally. The loss of low-affinity NGF-receptor (p75NGFr)-immunoreactive neurons differed for the toxins (AMPA-cc > QUIS-cc > IBO-cc), whereas treatment with NGF increased the size of the remaining neurons independently of the used toxin. NGF induced a p75NGFr-immunoreactive thickening around intracerebral arteries for all three toxins. Lesions of the NBM produced by IBO, QUIS, and AMPA resulted in a quantitatively different pattern of behavioral, biochemical, and histological deficits. The quantitatively different pattern of recovery after administration of NGF may be determined by the responsivity of the remaining neurons. Intracerebroventricular administration of NGF affected noncholinergic systems as well, resulting in decreased food intake and cerebrovascular hyperinnervation.
D000818:Animals; D001522:Behavior, Animal; D007051:Ibotenic Acid / Q000494:pharmacology*; D007150:Immunohistochemistry; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D009414:Nerve Growth Factors / Q000494:pharmacology*; D016318:Quisqualic Acid / Q000494:pharmacology*; D051381:Rats; D011916:Rats, Inbred F344; D013377:Substantia Innominata / Q000187:drug effects* / Q000276:immunology; D013997:Time Factors; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000494:pharmacology*
D009414:Nerve Growth Factors; D007051:Ibotenic Acid; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; D016318:Quisqualic Acid