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Hala Manal

University of St Andrews, United Kingdom

Presentation Title:

Investigating the crucial molecular and cellular mechanisms underpinning the role of leptin and ghrelin and their receptors on hippocampal neurons and episodic-like memory scores

Abstract

Our cellular understanding of how metabolic hormones contribute to Alzheimer’s Disease (AD) development is not yet precisely understood. Key neuroendocrine research findings have shown that leptin, ghrelin, and dopamine exert neuroprotective effects. Additionally, behavioural research has shown that environmental enrichment can improve episodic memory performance by promoting cell proliferation. As episodic memory loss is one of the first clinical symptoms of Alzheimer's disease, the molecular and cellular relationship between this cognitive function and hormone receptor expression was examined. An Enzyme-Linked Immunosorbent Assay (ELISA) was used to measure ObR, GHSR1-α, and tyrosine hydroxylase levels to assess the molecular expression underlying the role of leptin, ghrelin, and dopamine. To determine the effect of hormonal treatment on cell survival, murine hippocampal (HT-22) cells were treated with leptin and ghrelin at varying concentrations and time points ranging from 6 hours to 96 hours. Most notably, these findings revealed that ghrelin receptor levels are significantly higher in rodents reared in an enriched environment and that 25nM ghrelin significantly increases cell count. However, there was no correlation between receptor levels and episodic-like memory scores. The cellular results revealed that ghrelin treatment significantly increases cell count and reduces cell membrane damage in a time-dependent manner, measured by Lactate Dehydrogenase (LDH) release. LDH levels were significantly lower at 6-, 48-, and 72-hours post-treatment. This suggests that ghrelin plays a role in cell survival by altering cell membrane integrity. This evidence implies that GHSR-1α-mediated episodic memory increase is related to hippocampal-cell-associated memory enhancement. This result adds to the limited available literature on ghrelin’s role in episodic-like memory function. It provides evidence for ghrelin treatment or GHSR-1α receptor modulation as a potential therapeutic candidate for neurodegeneration, a key characteristic of AD pathology. Future studies should determine the value of manipulating metabolic hormone function to mediate neurogenesis or neurodegeneration.

Biography

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