Melatonin alleviates behavioral deficits associated with apoptosis and cholinergic system dysfunction in the APP 695 transgenic mouse model of Alzheimer's disease

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 beta-amyloid (Abeta)-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 Abeta deposition in frontal cortex of APP 695 Tg mice. However, melatonin decreased the Abeta 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 Abeta-mediated disease progression.

Centella asiatica extract selectively decreases amyloid β levels in hippocampus of Alzheimer's disease animal model

“…The effect of CaE on fibrillar amyloid in the hippocampus has not yet been determined. Dense-core plaque formation has recently been shown to occur predominantly associated with the vasculature in PSAPP mice suggesting 18 M. DHANASEKARAN ET AL. transgenic mice model of Alzheimer's disease (Feng et al, 2004;Migliore et al, 2005;Wang et al, 2005). In the present study, CaE inhibited the damage of the supercoiled form of the plasmid DNA due to exposure to hydrogen peroxide and UV light, and thus prevented the formation of single-strand or double-strand breaks.…”

Expression and Cerebral Function of Amyloid Precursor Protein After Rat Traumatic Brain Injury

“…Intracellular entry of Ca 2+ activates Ca 2+ -dependent signal pathways and can induce neural cell death. Additionally, choline acetyltransferase (ChAT) activity was decreased in the frontal cortex and hippocampus of APP 695 transgenic mice, an Alzheimer model overexpressing APP, and increased the number of apoptotic neurons (Feng et al, 2004). These APP 695 transgenic mice exhibit increased learning and memory impairment (Feng et al, 2004).…”

“…Additionally, choline acetyltransferase (ChAT) activity was decreased in the frontal cortex and hippocampus of APP 695 transgenic mice, an Alzheimer model overexpressing APP, and increased the number of apoptotic neurons (Feng et al, 2004). These APP 695 transgenic mice exhibit increased learning and memory impairment (Feng et al, 2004). In the present study, in the anti-APP antibody group there was an increase in the number of MAP-2-positive cells and a reduction in the arrival time to platform versus the PBS group.…”

Melatonin in Edible and Non-Edible Plants

“…26 Consequently, melatonin can be used for healing of muscle diseases, Parkinson and Alzheimer's due to antioxidant and neuroprotective affects. [27][28][29][30][31] Melatonin is widely used for sleep disorders such as jetlag and insomnia. 32 Its administration can relieve daytime and overnight sleep.…”