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Chronic oxotremorine treatment ameliorates depressive phenotype in a rodent model of Alzheimer’s disease

Nair DV, Al-Badri MM, Peng H, Schenkman N, Pacheco-Quinto J, Eckman CB, Iacono D, Eckman EA (2014) Chronic oxotremorine treatment ameliorates depressive phenotype in a rodent model of Alzheimer’s disease. Neuroscience 2014 Abstracts 670.03. Society for Neuroscience, Washington, DC.

Summary: Alzheimer’s disease (AD) is a progressive neurodegenerative condition that is characterized by changes to brain structure and function. It is estimated that depression and other neuropsychiatric symptoms occur in up to 90% of AD patients, yet the neurobiological basis of these symptoms and their influence on the clinical course of AD remain unclear. Using a rat model of AD-like basal forebrain cholinergic cell loss, our lab has previously shown that central administration of a muscarinic receptor agonist, oxotremorine, for 4 weeks could induce hippocampal neurogenesis and reverse the spatial working memory deficit triggered by cholinergic denervation. Preliminary experiments conducted with this model in our lab also revealed a depressive phenotype emerging between 11 and 15 weeks after cholinergic denervation. The depressive phenotype was detected using a sucrose consumption test and further confirmed by forced swim test. The goal of the present study was to determine whether effects of chronic oxotremorine treatment could ameliorate the depressive phenotype observed after selective cholinergic cell loss in the basal forebrain. Adult female Sprague Dawley rats were injected intracerebroventricularly (icv) with the immunotoxin 192-IgG-saporin (SAP), to induce AD-like basal forebrain cholinergic cell loss. After a 5 week recovery period, the rats then received 8 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. Biochemical analysis of a range of markers including tryptophan hydroxylase, the rate limiting enzyme for synthesis of serotonin, was performed after extraction of the brains following the behavioral tests. Results of these experiments demonstrate that oxotremorine treatment prevents the development of the depressive phenotype in SAP-lesioned rats. A number of oxotremorine-treated rats showed increases in tryptophan hydroxylase, suggesting a possible mechanism for the improved behavioral phenotype Based on these data, we propose that 192-IgG saporin lesioned rats may be an effective model for studying the pathophysiology and therapeutic modulation of age- and neurodegeneration-related neuropsychiatric symptoms such as depression.

Related Products: 192-IgG-SAP (Cat. #IT-01)