title: 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.
authors.affiliation: Faculty of Biology, Center for Laser Microscopy, University of Belgrade, Belgrade, Serbia.
authors.forename: Danijela
authors.initials: D
authors.lastname: Bataveljic
authors.forename: Jelena
authors.initials: J
authors.lastname: Petrovic
authors.forename: Katarina
authors.initials: K
authors.lastname: Lazic
authors.forename: Jasna
authors.initials: J
authors.lastname: Saponjic
authors.forename: Pavle
authors.initials: P
authors.lastname: Andjus
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001930:Brain Injuries / Q000139:chemically induced / Q000150:complications / Q000473:pathology*; D039481:CD11b Antigen / Q000378:metabolism; D059329:Cholinergic Neurons / Q000473:pathology*; D003714:Denervation / Q000379:methods; D004195:Disease Models, Animal; D018690:Excitatory Amino Acid Agonists / Q000633:toxicity; D007839:Functional Laterality; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D007051:Ibotenic Acid / Q000633:toxicity; D008297:Male; D009457:Neuroglia / Q000187:drug effects / Q000378:metabolism*; D045042:Pedunculopontine Tegmental Nucleus / Q000293:injuries / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar
chemical_list: D039481:CD11b Antigen; D018690:Excitatory Amino Acid Agonists; D005904:Glial Fibrillary Acidic Protein; D007051:Ibotenic Acid
keywords: astroglia; excitotoxic lesion; microglia; nucleus basalis; pedunculopontine tegmental nucleus