Melatonin enhances cognition and hippocampal neurogenesis in animal model of Alzheimer's disease and retinal degeneration

Abstract

Alzheimer’s disease (AD) is a neurodegenerative disorder, and it is mainly characterized by the presence of amyloid-beta plaques and neurofibrillary tangles. These hallmark pathologies of AD promote impairment of hippocampal neurogenesis, neuronal loss, and subsequently lead to neurocognitive deficits as well as neuropsychiatric problems. Many empirical studies demonstrated that AD shares similar pathologies and mechanisms with retinal degeneration, a form of neurodegeneration leading to blindness. Accumulating evidence has also indicated the presence of neurocognitive impairments and neuropsychiatry symptoms in retinal degeneration, suggesting potential alterations of hippocampal neurogenesis and neuronal survivability which are similar to AD. Despite much research on treatments for both diseases, there is still no effective treatment available. The endogenous hormone melatonin has been found to have therapeutic effects against the AD pathology and the photoreceptor degeneration in retinal degeneration. However, no research has been conducted focusing on the neurogenesis aspect of melatonin in ameliorating behavioral alterations in both diseases. In this thesis, I have investigated the therapeutic potential of melatonin on hippocampal neurogenesis in AD and retinal degeneration. My results revealed that melatonin could attenuate the impairment of hippocampal neurogenesis and improve behavioral deficits in an animal model of AD. The findings showed that the improvement of behavioral deficits in AD was mediated through the reduction of Aβ plaque burden and enhancement of hippocampal neurogenesis. Next, I have shown the neuroprotective effects of melatonin on visual-behavioral deficits and hippocampal neurogenesis in an animal model of retinal degeneration. I have found that melatonin could ameliorate the loss of retinal cells and promote visual cortical plasticity, thereby improve the visual function. It also enhanced hippocampal neurogenesis to rescue the loss of mature, as well as immature neurons in retinal degeneration. Furthermore, these neuroprotective effects of melatonin maintained the functional interactions and integrity of the retina, visual cortex, and hippocampus by improving both the visual and behavioral deficits in retinal degeneration. Overall, my thesis presents a novel aspect of melatonin on neuroprotective functions and hippocampal neurogenesis in both the AD and retinal degeneration to rescue behavioral deficits in animal models.