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Intraventricular IgG192-saporin lesions lead to altered 5-HT2A receptor levels in the hippocampus

Pedersen AF, Kostova V, Christensen E, Veng LM, Lohals R, Knudsen GM, Aznar S (2005) Intraventricular IgG192-saporin lesions lead to altered 5-HT2A receptor levels in the hippocampus. Neuroscience 2005 Abstracts 559.17. Society for Neuroscience, Washington, DC.

Summary: Background: Alzheimer’s disease (AD) is the most frequent neurodegenerative disorder in humans. One of the traits of the disease is the presence in the brain of beta-Amyloid plaques and loss of cholinergic neurons in the basal forebrain. Other transmittersystems especially serotonin may be involved in the patophysiology of AD. Clinical studies have observed a higher incidence of depression among AD patients and a higher risk of developing dementia when diagnosed with major depression. It is known that serotonin and serotonin receptors, among them 5-HT2A receptors (5-HT2AR), are involved in depression. Interestingly, recent PET-studies have shown lower 5-HT2AR levels in entorhinal cortex and hippocampus in early stages of AD. Objectives: Our aim was to investigate whether 5-HT2AR levels were affected in the hippocampus after lesioning the cholinergic neurons in the basal forebrain, thereby highlighting a possible interaction between the serotonergic and the cholinergic transmitter systems. Methods: Intraventricular injection of 5ug IgG192-Saporin or saline in adult Wistar male rats. After 20 weeks the rats were sacrificed and the hippocampus were isolated. After homogenisation the levels of 5-HT2AR were determined by western blot. Results: Downregulation of the 5-HT2AR levels were observed after 20 weeks. 5-HT2AR levels for animals receiving IgG192-Saporin for 1, 2 and 4 weeks will also be investigated. Conclusion: Our results show a direct effect of cholinergic lesions on hippocampal 5-HT2AR. This may be explained by a compensatory effect of the serotonergic system for the loss of cholinergic input as there may be a balance between these two systems in the hippocampus.

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

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