Leptin peptides and the Implications on Alzheimer’s Disease
MICHELE LONGONI CALIO, Fernando H Massinhani, Marimelia Aparecida Porcionatto, Darci Souza Marinho- Psychiatry and Mental health
- Cellular and Molecular Neuroscience
- Geriatrics and Gerontology
- Neurology (clinical)
- Developmental Neuroscience
- Health Policy
- Epidemiology
Abstract
Background
Obesity and neurodegeneration are growing health problems worldwide. Alzheimer’s disease (AD) is the most prevalent cause of progressive dementia in the elderly population. AD is characterized by the combined presence of extracellular plaques formed by β‐amyloid peptide and intraneuronal neurofibrillary tangles of abnormally hyperphosphorylated Tau protein. Several studies have shown that obesity is a risk factor for dementia. Leptin, initially described as the hormone responsible for controlling food intake and energy expenditure, also has other important physiological functions related to neuronal activity, proliferation and protection. With the discovery that neurogenesis persists in the brain of adult mammals, including brain regions affected by AD, many studies aim to stimulate this physiological process in various areas of the brain for the treatment of neurodegenerative diseases to repair and/or prevent neural loss. These regions also express the long form of the LepRb leptin receptor and are the first regions to be affected by chronic neurocognitive deficits.
Method
Given the neurogenic potential of leptin, the main objective of this study is to analyze and compare the action of this hormone with synthetic peptides (PEP) on cell proliferation, differentiation and Aβ plaque formation in two of the main neurogenic niches in AD model mice.
Result
The expression of glial, neuoblast and Aβ markers were detected by immunohistochemistry. We observed that animals treated with PEP4 had a significant increase in the proportion of BrdU/DCX+ cells regardless the age and animal model. Our results also show that treatment with PEP4 was able to significantly decrease the amount of Aβ plaques in the hippocampus of AD model animals. However, it is observed that this decrease is significantly smaller than when compared to that produced by leptin, demonstrating that it is more effective in reducing the number of Aβ plaques in the hippocampus region.
Conclusion
We believe that a better understanding of the mechanisms of the pathological processes that cause AD and how altered leptin signaling affects these processes could lead to the development of early therapies for the treatment of Alzheimer’s disease.