Affiliations: Department of Biological Sciences, California State
University Los Angeles, 5151 State University Drive, Los Angeles, CA 90032,
USA | Department of Biomedical Sciences, Charles R. Drew
University of Medicine & Science, 1731 East 120th Street, Los Angeles, CA
90059, USA
Abstract: Purpose: To investigate the plastic capacity of the cholinergic
system in a partial animal model of Alzheimer's disease. Methods: Rats received unilateral lesions of the horizontal diagonal
band of Broca (HDB) using a cholinergic-specific toxin, 192 IgG-saporin. After
the appropriate survival time (2, 4, 8, 12 and 24 weeks post-lesion) rats were
sacrificed and the brains were prepared for histology. Immunocytochemical and
morphometric techniques were employed to quantify the cholinergic neurons
surviving the lesion and to measure the density of cortical cholinergic
fibers. Results: Cell counts revealed on average a 60% reduction in
cholinergic neurons on the lesioned side, compared to the spared side. This
cell loss was permanent, that is, there was no significant change in the amount
of cell loss over time. In correlation with this cell loss, cholinergic fibers
in the target area, the entorhinal cortex (EC), were also reduced such that the
density of acetylcholinesterase (AChE)-stained fibers on the lesioned side was
44% of the spared side. The density of cholinergic fibers in the EC increased
significantly between 2 and 12 weeks post-lesion (p = 0.0216) but remained
stable at that level by 24 weeks after the lesion. Conclusions: Following a cholinergic-specific lesion, a compensatory
mechanism is activated in the basal forebrain cholinergic system, such that
surviving neurons, projecting to the same target, extend their terminals to
occupy the denervated area. It remains to be investigated whether these sprouts
are able to establish proper synaptic connections and make a functional
recovery in this particular system.
Keywords: plasticity, basal forebrain, cholinergic system, outgrowth, acetylcholine, immunocytochemistry, rat
