The single most impactful factor affecting quality of life, health and mental health is social support. Social support is also a well-established risk factor for Alzheimer?s Disease (AD). Positive social support reduces, while negative social support increases risk of AD-related dementia. Surprisingly, little is known regarding the neural mechanisms by which social support affects AD, or expression of basic molecular processes related to AD. This lack of knowledge severely limits our ability to advance AD research and identify effective treatment strategies. Our long-term goal is to elucidate the neural mechanism by which social support benefits mental and neurological health so that therapeutic strategies can be developed for treatment and prevention of mental and neurological disorders. The overall goal of this application is to identify how social support, modeled in rats, affects expression of AD-related amyloid plaque precursors and neuroprotective factors. Our central hypothesis is that positive social support will reduce ?AD-advancing factors? and/or enhance ?AD-protective factors? while negative social support will have the opposite effect. Our lab is uniquely qualified to obtain this goal because we have developed social training paradigms in rats that approximate different levels of social support, including social isolation, negative, neutral and positive social support. We will combine our social support expertise with Dr. Debomoy Lahiri?s expertise with AD-related biomarkers to investigate how social support regulates expression of AD-associated processes. Specifically, we will use our social support gradient model to identify the extent to which quality of social support affects ?AD-advancing factors? (Aim 1), ?AD- protective factors? (Aim 2) and identify putative mechanisms by which social support regulates these factors (Aim 3). The rationale for the proposed research is that identifying the acute effects of social support on AD- related precursors and neuroprotection in ?normal? rats will 1) provide further insights into putative mechanisms by which social cues alter emotional responses, thus within the scope of parent R01, 2) provide initial insights into putative mechanisms by which social support may reduce risk of AD, and 3) stimulate a new research projects investigating long-term beneficial effects of social support in AD models to advance understanding and lead to novel therapeutic strategies for treating/preventing AD. We will use our innovative social support gradient model combined with targeted molecular techniques to pursue the following specific aims: 1: Identify the extent to which social support alters APP and APP processing enzymes? levels and mRNA. 2: Identify the extent to which social support alter BDNF, NMDAR, PSD95, SNAP25, and SYPH levels and mRNA. 3: Identify the extent to which social support regulate the regulators of AD associated molecular pathways: microRNA levels.
The proposed research is relevant to public health because it will increase our systematic/mechanistic understanding of how social support impacts basic Alzheimer?s Disease (AD) related neural processes, which will provide novel insights into our understanding of putative mechanism by which social support reduces risk of AD. This project is relevant to the NIH?s mission because it will lead to increased understanding of AD risk factors and provide insights into ways to eventually reduce the burden of AD.
