Glial Response in the Rat Models of Functionally Distinct Cholinergic Neuronal Denervations
Abstract:
Alzheimer's disease (AD) involves selective loss of basal forebrain
cholinergic neurons, particularly in the nucleus basalis (NB).
Similarly, Parkinson's disease (PD) might involve the selective loss of
pedunculopontine tegmental nucleus (PPT) cholinergic neurons. Therefore,
lesions of these functionally distinct cholinergic centers in rats might
serve as models of AD and PD cholinergic neuropathologies. Our previous
articles described dissimilar sleep/wake-state disorders in rat models
of AD and PD cholinergic neuropathologies. This study further examines
astroglial and microglial responses as underlying pathologies in these
distinct sleep disorders. Unilateral lesions of the NB or the PPT were
induced with rats under ketamine/diazepam anesthesia (50 mg/kg i.p.) by
using stereotaxically guided microinfusion of the excitotoxin ibotenic
acid (IBO). Twenty-one days after the lesion, loss of cholinergic
neurons was quantified by nicotinamide adenine dinucleotide
phosphate-diaphorase histochemistry, and the astroglial and microglial
responses were quantified by glia fibrillary acidic protein/OX42
immunohistochemistry. This study demonstrates, for the first time, the
anatomofunctionally related astroglial response following unilateral
excitotoxic PPT cholinergic neuronal lesion. Whereas IBO NB and PPT
lesions similarly enhanced local astroglial and microglial responses,
astrogliosis in the PPT was followed by a remote astrogliosis within the
ipslilateral NB. Conversely, there was no microglial response within the
NB after PPT lesions. Our results reveal the rostrorostral PPT-NB
astrogliosis after denervation of cholinergic neurons in the PPT. This
hierarchically and anatomofunctionally guided PPT-NB astrogliosis
emerged following cholinergic neuronal loss greater than 17\% throughout
the overall rostrocaudal PPT dimension. (c) 2014 Wiley Periodicals, Inc.
Keywords:
astroglia; microglia; excitotoxic lesion; pedunculopontine tegmental nucleus; nucleus basalisSource:
Journal of Neuroscience Research, 2015, 93, 2, 244-252
DOI: 10.1002/jnr.23483
ISSN: 1097-4547