Rennie KE, Ward C, Fréchette M, Pappas BA (2009) Effects of combined neonatal cholinergic lesion and chronic cerebral hypoperfusion on CA1 cytoarchitecture. Neuroscience 2009 Abstracts 736.23/M38. Society for Neuroscience, Chicago, IL.
Summary: Neonatal lesioning of the basal forebrain cholinergic (BFC) system alters cytoarchitecture of pyramidal cells in both the hippocampus and neocortex of the adult rat, indicating a role for the BFC in forebrain development. In addition to altering forebrain development, neonatal cholinergic lesion may also exacerbate the brain’s response to pathological factors that emerge as the brain ages. One factor that might interact with BFC lesion is reduced cerebral blood flow (hypoperfusion). Examining this interaction is especially interesting because both BFC degeneration and reduced cerebral blood flow are characteristics of Alzheimer’s disease. In the rat, chronic cerebrovascular insufficiency by itself reportedly causes the degeneration of hippocampal CA1 pyramidal cells, alters amyloid processing and produces spatial memory impairments. We hypothesized that neonatal cholinergic lesion using the cholinotoxin 192-IgG-saporin would render the hippocampus more vulnerable to the neuropathological effects of chronic forebrain hypoperfusion induced by permanent bilateral occlusion of the carotid arteries (2VO). We previously reported that combined BFC lesion and 2VO impaired working memory in the Morris water maze and increased anxiety-like behaviours on the elevated plus apparatus, whereas neither of these treatments alone caused any of these effects. Here we report the effects of neonatal BFC lesion, 2VO, or their combined application on hippocampal CA1 cytoarchitecture using quantitative Golgi analysis. Rats subjected to 2VO showed increased apical branch length and spines, and increased basal spines. Neonatal BFC lesion on its own had only restricted effects on apical branch length at certain branch orders and no effect on spines. However, at a number of branch orders the stimulating effect of 2VO on apical spines occurred only in animals subjected to neonatal BFC lesion, indicating that this lesion modulated the response to 2VO. To our knowledge, this is the first examination of the effects of 2VO on CA1 neuron cytoarchitecture. Surprisingly, it increased rather than decreased dendritic length and spines. Furthermore, while the BFC lesion had minimal effects on its own, it was permissive to some of the effects of 2VO on dendritic spines. Taken together with our previous data, this study suggests that pre-existing cholinergic dysfunction alters aspects of both the behavioural and neural consequences of chronic hypoperfusion. These results may have implications for Alzheimer’s disease where cholinergic dysfunction and hypoperfusion are co-expressed
Related Products: 192-IgG-SAP (Cat. #IT-01)