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Journal of Neuroscience, Vol 13, 5263-5276, Copyright © 1993 by Society for Neuroscience
Atrophy but not death of adult septal cholinergic neurons after ablation of target capacity to produce mRNAs for NGF, BDNF, and NT3
MV Sofroniew, JD Cooper, CN Svendsen, P Crossman, NY Ip, RM Lindsay, F Zafra and D Lindholm
Department of Anatomy, University of Cambridge, United Kingdom.
The effect of unilateral excitotoxic ablation of hippocampal neurons was
investigated on (1) the local production of mRNA for NGF and related
neurotrophins, (2) the amount of NGF protein in the septal region, and (3)
the viability and appearance of afferent septal cholinergic neurons in
adult rats. After near complete ablation of hippocampal neurons, total
levels of NGF, brain-derived neurotrophic factor (BDNF), and neurotrophin-3
(NT3) mRNA measured by quantitative Northern blot analysis in the
hippocampal remnant fell significantly, to less than 25% of control values
by 28 d and to less than 9% by 300 d. In the septal region ipsilateral to
such lesions, NGF protein levels measured by ELISA fell significantly, to
about 35% of control values, but the number of immunohistochemically
detected cholinergic neurons did not decline significantly for up to 500 d.
Instead, the cholinergic neurons persisted in an atrophied state,
exhibiting severe shrinkage and reduced staining for the
transmitter-synthesizing enzyme ChAT. The parameters of cell size and ChAT
staining intensity correlated significantly with the amount of hippocampal
tissue present. These findings indicate that in adult rats, target-derived
NGF, BDNF, and NT3 do not regulate the survival of septal cholinergic
neurons in proportion to the number of target neurons present. Moreover,
the findings suggest that one or more of these target-derived neurotrophins
regulate the structural and chemical phenotype of these neurons in the
adult.
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