title: Premature Aging Phenotype in Mice Lacking High-Affinity Nicotinic Receptors: Region-Specific Changes in Layer V Pyramidal Cell Morphology.
abstract: The mechanisms by which aging leads to alterations in brain structure and cognitive deficits are unclear. Α deficient cholinergic system has been implicated as one of the main factors that could confer a heightened vulnerability to the aging process, and mice lacking high-affinity nicotinic receptors (β2(-/-)) have been proposed as an animal model of accelerated cognitive aging. To date, however, age-related changes in neuronal microanatomy have not been studied in these mice. In the present study, we examine the neuronal structure of yellow fluorescent protein (YFP(+)) layer V neurons in 2 cytoarchitectonically distinct cortical regions in wild-type (WT) and β2(-/-) animals. We find that (1) substantial morphological differences exist between YFP(+) cells of the anterior cingulate cortex (ACC) and primary visual cortex (V1), in both genotypes; (2) in WT animals, ACC cells are more susceptible to aging compared with cells in V1; and (3) β2 deletion is associated with a regionally and temporally specific increase in vulnerability to aging. ACC cells exhibit a prematurely aged phenotype already at 4-6 months, whereas V1 cells are spared in adulthood but strongly affected in old animals. Collectively, our data reveal region-specific synergistic effects of aging and genotype and suggest distinct vulnerabilities in V1 and ACC neurons.
authors.affiliation: Neurophysiology Laboratory, Division of Developmental Biology, Biomedical Research Foundation of the Academy of Athens, Athens 115 27, Greece.
authors.forename: Eleni
authors.initials: E
authors.lastname: Konsolaki
authors.affiliation: Neurophysiology Laboratory, Division of Developmental Biology, Biomedical Research Foundation of the Academy of Athens, Athens 115 27, Greece.
authors.forename: Irini
authors.initials: I
authors.lastname: Skaliora
mesh_terms: D000375:Aging / Q000378:metabolism / Q000473:pathology; D019588:Aging, Premature / Q000378:metabolism / Q000473:pathology*; D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D002540:Cerebral Cortex / Q000098:blood supply / Q000254:growth & development / Q000378:metabolism / Q000473:pathology*; D004195:Disease Models, Animal; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010641:Phenotype; D017966:Pyramidal Cells / Q000378:metabolism / Q000473:pathology*; D011978:Receptors, Nicotinic / Q000172:deficiency* / Q000235:genetics
chemical_list: D001426:Bacterial Proteins; D008164:Luminescent Proteins; D011978:Receptors, Nicotinic; C054562:yellow fluorescent protein, Bacteria
keywords: aging; anterior cingulate cortex; primary visual cortex; selective vulnerability; β2 nAChR