Morphological response of axotomized septal neurons to nerve growth factor

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Abstract
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‐μm‐thick sections. In 1‐μm‐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‐μm‐ or 1‐μm‐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. In addition, the lesion‐induced appearance of enlarged ChAT‐IR processes was avoided, and NGF prevents some of the degenerative changes that occur in non‐ChAT‐IR septal neurons after fimbria‐fornix aspiration.