Nair DV, Al-Badri MM, Peng H, Pachego-Quinto J, Eckman CB, Iacono D, Eckman EA (2015) Preliminary investigation on the antidepressive effect of chronic oxotremorine treatment in a rodent model of Alzheimer’s disease. Neuroscience 2015 Abstracts 40.29/C34. Society for Neuroscience, Chicago IL.
Summary: Alzheimer’s disease (AD) is a progressive neurodegenerative disease and the rate of progression varies from individual to individual. A great deal of evidence supports the idea that depression and other neuropsychiatric conditions co-exist with cognitive decline. However, the neurobiological basis of these symptoms and their influence on the clinical course of AD remain unclear. Our lab has shown previously that the 192-IgG saporin rat model of AD-like basal forebrain cholinergic cell loss exhibits a depression-like phenotype that develops months after the well-described impairment in spatial working memory. Furthermore, we have shown that chronic intracerebroventricular administration of the muscarinic agonist oxotremorine reverses both spatial working memory deficits and the depression-like behavior triggered by cholinergic denervation, and induces hippocampal neurogenesis. Current experiments are focused on determining additional pathological correlates of depression in this model and how they may be modulated by muscarinic agonists. To induce AD-like basal forebrain cholinergic cell loss, adult female Sprague Dawley rats were injected intracerebroventricularly (icv) with the immunotoxin 192-IgG-saporin (SAP) or saline as control (SHAM). After a 5 week recovery period, the rats received either 2 or 6 weeks of icv infusion of either oxotremorine or vehicle (saline) via osmotic minipump. Behavioral testing to assess the depressive phenotype was carried out using the sucrose consumption test every 2 weeks during oxotremorine treatment. The phenotype was further confirmed by forced swim test. The levels of ChAT, tryptophan hydroxylase (TPH), muscarinic receptors and FosB and ΔFosB were assessed in the hippocampus, basal forebrain, and orbitofrontal cortex by western blot and immunohistochemistry. Our preliminary results show increases in TPH, M1 receptors and FosB in the hippocampus, basal forebrain, and orbitofrontal cortex of a subset of treated animals, but no changes ChAT or ΔFosB. Further experiments are in progress to determine if there are changes in the expression of these and additional proteins in other brain regions including the nucleus accumbens, an area involved in activational aspects of motivation which also contributes to behavioral disorders such as to depression. The results of these studies may provide new insight in understanding the molecular basis of depression and antidepressant action of oxotremorine thereby defining new targets for possible therapeutic intervention for depressive symptoms in AD.
Related Products: 192-IgG-SAP (Cat. #IT-01)