Present address: Section of Endocrinology, Department of Internal Medicine Yale University, School of Medicine, New Haven, 06520-8020 CT, USA. E-mail: email@example.com
Melatonin alleviates behavioral deficits associated with apoptosis and cholinergic system dysfunction in the APP 695 transgenic mouse model of Alzheimer's disease
Article first published online: 28 JUN 2004
Journal of Pineal Research
Volume 37, Issue 2, pages 129–136, September 2004
How to Cite
Feng, Z., Chang, Y., Cheng, Y., Zhang, B.-l., Qu, Z.-w., Qin, C. and Zhang, J.-t. (2004), Melatonin alleviates behavioral deficits associated with apoptosis and cholinergic system dysfunction in the APP 695 transgenic mouse model of Alzheimer's disease. Journal of Pineal Research, 37: 129–136. doi: 10.1111/j.1600-079X.2004.00144.x
- Issue published online: 28 JUN 2004
- Article first published online: 28 JUN 2004
- Received February 6, 2004; accepted April 27, 2004.
- β-amyloid peptide;
- Alzheimer's disease;
- choline acetyltransferase;
Abstract: Melatonin is an endogenous antioxidant and free radical scavenger. A transgenic (Tg) mouse model for Alzheimer's disease mimics the accumulation of senile plaques, neuronal apoptosis and memory impairment. Previous studies indicated that melatonin reduced β-amyloid (Aβ)-induced neurotoxicity. In this study, after giving melatonin at 10 mg/kg to APP 695 transgenic (APP 695 Tg) mice for 4 months, we evaluated the long-term influence of melatonin on behavior, biochemical and neuropathologic changes in APP 695 Tg mice. Step-down and step-through passive avoidance tests suggested that 8-month-old APP 695 Tg mice showed decreases in step-down latency and step-through latency and increases in count of error throughout the entire learning trial and memory session, which suggested learning and memory impairment. However, melatonin alleviated learning and memory deficits. Additionally, choline acetyltransferase (ChAT) activity also decreased in the frontal cortex and hippocampus of APP 695 Tg mice compared with non-Tg littermates. Melatonin supplementation increased ChAT activity in the frontal cortex and hippocampus. DNA fragmentation was present in the frontal cortex of the APP 695 Tg mice; melatonin reduced the number of apoptotic neurons. Congo Red staining and Bielschowsky silver impregnation both showed the apparent extracellular Aβ deposition in frontal cortex of APP 695 Tg mice. However, melatonin decreased the Aβ deposits. Our results indicate that neuroprotection by melatonin is partly related to modulation of apoptosis and protection of the cholinergic system. Early rational melatonin interventions may be one of the most promising strategies in the development of approaches to retard or prevent Aβ-mediated disease progression.