Involvement of an altered 5-HT -{6} receptor function in behavioral symptoms of Alzheimer's disease

We studied the hypothesis that disturbances in 5-HT_{6} receptor function in the temporal cortex may contribute to clinical symptoms of Alzheimer's disease (AD). 5-HT_{6} density and 5-HT levels were significantly decreased in a cohort of AD patients prospectively assessed for cognitive/behavio...

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Autores: Marcos, B. (Beatriz)|||/items/8d153f88-339f-44ba-a0e1-ba2671b164a5, Garcia-Alloza, M. (Mónica)|||/items/252ba83d-9798-4e6f-8edd-57310f48563e, Gil-Bea, F.J. (Francisco J.)|||/items/33abaa1d-cc6b-4ed9-b0eb-6daa654b1915, Chuang, T.T. (Tsu T.)|||/items/187824fe-b291-4580-b6c5-52c1f09cc1f5, Francis, P.T. (Paul T.)|||/items/3f9634b0-ace4-4708-95e8-bad74af3a9e9, Chen, C.P. (Christopher P.)|||/items/a1d5abd8-5b8b-4317-a82d-58223946b9fe, Tsang, S.W.T.Y. (Shirley W.T.Y.)|||/items/65a31dcd-b145-4629-844a-74020473bb8e, Lai, M.K. (Mitchell K.)|||/items/e615244e-18f4-49a8-91c7-4b593a803ce1, Ramírez-Gil, M.J. (María Javier)|||/items/2d48ae79-411f-45a1-bd65-bbee2aa118da
Tipo de recurso: artículo
Fecha de publicación:2008
País:España
Institución:Universidad de Navarra
Repositorio:Dadun. Depósito Académico Digital de la Universidad de Navarra
Idioma:inglés
OAI Identifier:oai:dadun.unav.edu:10171/20227
Acceso en línea:https://hdl.handle.net/10171/20227
Access Level:acceso abierto
Palabra clave:Adenylate cyclase
Gender
Neocortex
Psychosis
Descripción
Sumario:We studied the hypothesis that disturbances in 5-HT_{6} receptor function in the temporal cortex may contribute to clinical symptoms of Alzheimer's disease (AD). 5-HT_{6} density and 5-HT levels were significantly decreased in a cohort of AD patients prospectively assessed for cognitive/behavioral symptoms. cAMP formation after stimulation with the selective 5-HT_{6} receptor agonist E-6801 was significantly lower (p<0.01) in AD (170.02 +/- 27.53 pmol/mg prot.) compared to controls (823.33 +/-196.67). In addition, the ratio cAMP formation after stimulation with E-6801/5-HT_{6} receptor density was significantly lower (p< 0.01) in AD (6.67 +/- 0.83) compared to controls (16.67 +/- 3.33). Splitting these results by sex, 5-HT_{6} receptor activation was significantly lower (p< 0.01) in AD females compared to males (121.67 +/- 30.02 vs. 231.67 +/- 34.17 pmol/mg prot). 5-HT_{6} density and 5-HT levels were significantly correlated (p < or = 0.01) in both controls and AD patients, although in AD, this correlation was lost in females. Psychosis factor was the best predictor of reduced 5-HT levels or adenylate cyclase activity after E-6801 stimulation, the former result being due to females. It may be suggested that psychotic symptoms may be related to a dysregulation of 5-HT_{6} activation by 5-HT in the temporal cortex. These results are discussed in terms of purported influence of sex and therapeutical approaches to psychosis in AD.

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