期刊
JOURNAL OF PINEAL RESEARCH
卷 54, 期 3, 页码 346-358出版社
WILEY
DOI: 10.1111/jpi.12037
关键词
amyloid precursor protein; cholinergic degeneration; Down syndrome; learning and memory; melatonin; Ts65Dn
资金
- Instituto de Formacion e Investigacion Marques de Valdecilla [FMV-API 10/19]
- Spanish Ministry of Economy and Competitiveness [BFU2011-24755]
Ts65Dn mice (TS), the most commonly used model of Down syndrome (DS), exhibit phenotypic characteristics of this condition. Both TS mice and DS individuals present cognitive disturbances, age-related cholinergic degeneration, and increased brain expression of -amyloid precursor protein (APP). These neurodegenerative processes may contribute to the progressive cognitive decline observed in DS. Melatonin is a pineal indoleamine that has been reported to reduce neurodegenerative processes and improve cognitive deficits in various animal models. In this study, we evaluated the potentially beneficial effects of long-term melatonin treatment on the cognitive deficits, cholinergic degeneration, and enhanced APP and -amyloid levels of TS mice. Melatonin was administered for 5months to 5- to 6-month-old TS and control (CO) mice. Melatonin treatment improved spatial learning and memory and increased the number of choline acetyltransferase (ChAT)-positive cells in the medial septum of both TS and CO mice. However, melatonin treatment did not significantly reduce APP or -amyloid levels in the cortex or the hippocampus of TS mice. Melatonin administration did reduce anxiety in TS mice without inducing sensorimotor alterations, indicating that prolonged treatment with this indoleamine is devoid of noncognitive behavioral side effects (e.g., motor coordination, sensorimotor abilities, or spontaneous activity). Our results suggest that melatonin administration might improve the cognitive abilities of both TS and CO mice, at least partially, by reducing the age-related degeneration of basal forebrain cholinergic neurons. Thus, chronic melatonin supplementation may be an effective treatment for delaying the age-related progression of cognitive deterioration found in DS.
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