Poster abstracts
Poster number 102 submitted by Sabrina Mackey-Alfonso
The Effect of High Fat Diet on Neuroinflammation, Synaptic Plasticity, and Pathology in the 3xTg-AD Mouse Model
Sabrina Mackey-Alfonso (NGP), Michael Butler (IBMR), Alberto Williams-Medina (IBMR), Nicholas Deems (NGP), Ashton Taylor (IBMR)
Abstract:
Alzheimer’s Disease (AD) is a neurodegenerative disease that presents with the hallmark pathology of neurofibrillary tau tangles and amyloid beta (AB) plaques and ultimately results in memory impairment. High fat diet (HFD) consumption has been shown to increase the risk of developing AD in humans and cause neuroinflammation and memory impairment in wild type animal models. However, the underlying mechanisms linking diet to AD risk is not well-studied. Thus, this project serves to investigate the effect of HFD consumption on 1) neuroinflammation and synaptic plasticity genes in the hippocampus and amygdala and 2) the severity of AD pathology in the hippocampus in a 3xTg-AD mouse model. Following the consumption of either standard chow or short-term HFD, mice (4-7 month-old) were transcardially saline-perfused and the hippocampus and amygdala were dissected for qPCR analysis of inflammatory and synaptic plasticity genes. In a separate cohort, mice were saline-perfused, and brains were post-fixed in 4% paraformaldehyde and processed for immunohistochemistry (DAB) staining of phosphorylated tau (AT8) and AB staining in the CA1 region of the hippocampus. Short-term HFD significantly increased the level of proinflammatory markers in the hippocampus and amygdala, including CD11b (p < 0.001), HMGB1 (p < 0.01), and TNF (p < 0.01). HFD also caused an alteration in synaptic plasticity genes in both the hippocampus and amygdala seen through an increase in a postsynaptic marker, PSD95, and a decrease in a presynaptic marker, synaptophysin (p<0.05). Our DAB data show HFD consumption increased the number and size of AT8 and AB puncta in the hippocampus of 3xTg-AD mice. These data suggest HFD consumption increases neuroinflammation, alters synaptic plasticity genes, and accelerates AD pathology in 3xTg-AD mice. Future studies will investigate the impact of HFD on learning and memory in AD mice and the cellular mechanisms driving these diet-induced inflammatory and pathological changes
Keywords: Alzheimers Disease, neuroinflammation