Rennie KE, Frechette M, Pappas BA (2007) Behavioural consequences of combined cholinergic lesion and chronic cerebral hypoperfusion in rats. Neuroscience 2007 Abstracts 698.16/R26. Society for Neuroscience, San Diego, CA.
Summary: Chronic cerebral hypoperfusion compromises the health of hippocampal neurons, leading to a slowly emerging loss of pyramidal cells accompanied by spatial memory impairments in rats. Recent research suggests that vascular abnormalities resulting in insufficient cerebral blood flow or impaired nutrient delivery to the brain represent a significant risk factor for Alzheimer’s disease (AD) and may contribute to its pathogenesis. AD is also characterized by dysfunction of the forebrain cholinergic system. Since there is evidence that this system is involved in the control of local cerebral blood flow, we hypothesized that there would be synergistic effects of chronic cerebral hypoperfusion and cholinergic dysfunction. Hence, the aim of this study was to determine whether cholinergic dysfunction exacerbates the effects of cerebral hypoperfusion. Female rats were subjected to forebrain cholinergic lesion or control surgery by intraventricular infusion of the immunotoxin 192-IgG-saporin (192S) or phosphate buffered saline (PBS) on postnatal day 7. Six months later the rats underwent permanent bilateral occlusion of the carotid arteries (2VO), which causes moderate, chronic cerebral hypoperfusion, or sham surgery. When exposed to an open field 48, 72 and 96 hours after 2VO or sham surgery, the groups did not differ on measures of overall activity. However, the cholinergic lesion increased the latency to enter the centre area, and reduced both the number of centre entries and the percentage of total distance that was traveled in the inner squares. The lesion effects were mainly seen in the combined 192S/2VO group while 192S or 2VO alone produced only minor behavioural changes. Elevated plus testing 2 weeks after surgery revealed a reduction in open but not closed arm entries due to the cholinergic lesion. Interestingly, the effects of 2VO were dependent on the status of the cholinergic system. 2VO increased open arm entries in the PBS group, but decreased this behaviour in the 192S group. Thus on both the open field and elevated plus maze, the cholinergic lesioned rats displayed more anxious behaviour, particularly after 2VO. Finally, cholinergic lesion produced impairments on the working memory version of the Morris water maze. Again, this effect was most pronounced in the combined 192S/2VO group. This effect is unlikely to be due to motivational or sensorimotor deficits as all groups performed similarly on a cued platform version of the maze. Cholinergic lesion and 2VO appear to act synergistically to produce behavioural alterations, even at relatively early time points after 2VO. Their combined effects on CA1 pyramidal cell viability are currently under examination.
Related Products: 192-IgG-SAP (Cat. #IT-01)