Imipramine, in part through TNF-{alpha} inhibition, prevents cognitive decline and A{beta} accumulation in a mouse model of Alzheimer's disease. The Journal of pharmacology and experimental therapeutics [J Pharmacol Exp Ther] Journal article | | Title | Imipramine, in part through TNF-{alpha} inhibition, prevents cognitive decline and A{beta} accumulation in a mouse model of Alzheimer's disease. | | Author(s) | Chavant F, Deguil J, Pain S, Ingrand I, Milin S, Fauconneau B, Perault MC, Lafay-Chebassier C | | Institution | 1 CHU Poitiers; | | Source | J Pharmacol Exp Ther 2009 Nov 4. | | Abstract | Alzheimer's disease (AD), the most common form of dementia in the elderly, is a multifactoral pathology, characterized by cognitive deficits, increase in cerebral deposition of the beta-amyloid (Abeta) peptide, neurofibrillary tangles and neurodegeneration. Studies currently support a central role of neuroinflammation, through production of proinflammatory cytokines including excess tumor necrosis factor alpha (TNF-alpha) in the pathogenesis of AD, especially in Abeta-induced cognitive deficits. Imipramine, a tricyclic antidepressant, has potent anti-inflammatory and neuroprotective effects. This study investigate the effect of imipramine on alterations of long-term and short-term memories, TNF-alpha expression and APP processing induced by intracerebroventricular injection of Abeta25-35 in mice. Mice were treated with imipramine (10 mg/kg, i.p. once a day for 13 days) from the day after the Abeta25-35 injection. Memory function was evaluated in the water-maze (days 10-14) and Y-maze (day 9) tests. TNF-alpha levels and APP processing were examined in the frontal cortex and the hippocampus (day 14). Imipramine significantly prevented memory deficits caused by Abeta25-35 in the water-maze and Y-maze tests and inhibited the TNF-alpha increase in the frontal cortex. Moreover, imipramine decreased the elevated levels of Abeta both in frontal cortex and hippocampus with different modulations of APP and CTFs. So, imipramine prevents memory impairment through its intrinsic property to inhibit TNF-alpha and Abeta accumulation and may represent a potential candidate for AD treatment. | | Language | ENG | | Pub Type(s) | JOURNAL ARTICLE
| | PubMed ID | 19889791 |
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