Morphological response of axotomized septal neurons to nerve growth factor.
Septal efferent fibers from the neurons in the medial septal nucleus are destroyed by fimbria-fornix aspirative lesion. In the present study we used quantitative morphometric techniques to evaluate the response of these axotomized septal neurons to a constant infusion of nerve growth factor (NGF). By 2 weeks following the lesion, approximately 75% of the cholinergic neurons had degenerated in the untreated rats. The remaining cholinergic neurons showed few signs of the effect of the lesion when stained for a polyclonal antibody to ChAT and examined in 40-micron-thick sections. In 1-micron-thick sections the remaining ChAT-immunoreactive (IR) neurons also appeared no different from the intact ChAT neurons. However, non-ChAT-IR neurons had a shrunken nucleus, while all other morphometric parameters appeared normal. NGF infusion protected most of the ChAT-IR neurons from degenerating. The saved neurons had the same parameters as the undamaged ChAT-IR neurons when examined in either 40-micron- or 1-micron-thick sections. In addition, the shrunken appearance of the non-ChAT-IR neurons' nuclei was avoided by the NGF infusions. Enlarged ChAT-IR processes were evident in the dorsolateral quadrant of the septum following damage to the fimbria-fornix. NGF-infusions prevented the formation of these processes. Instead, in the treated animals the dorsal lateral quadrant contained a dense plexus of fine ChAT-IR varicosities. Taken together these results demonstrate that NGF not only can protect the cholinergic neurons from axotomy-induced degeneration but can also cause the saved neurons to maintain the same morphometric appearance as intact ChAT-IR neurons.(ABSTRACT TRUNCATED AT 250 WORDS)
Gage
F H
FH
Department of Neurosciences, University of California, San Diego, School of Medicine, La Jolla 92093.
Armstrong
D M
DM
Williams
L R
LR
Varon
S
S
D000818:Animals; D002452:Cell Count; D002795:Choline O-Acetyltransferase / Q000032:analysis; D002799:Cholinergic Fibers / Q000187:drug effects / Q000201:enzymology / Q000502:physiology*; D005260:Female; D009414:Nerve Growth Factors / Q000494:pharmacology*; D009416:Nerve Regeneration / Q000187:drug effects*; D051381:Rats; D011919:Rats, Inbred Strains; D012686:Septal Nuclei / Q000187:drug effects / Q000502:physiology*
D009414:Nerve Growth Factors; D002795:Choline O-Acetyltransferase