- Email: [email protected]
ROLE OF SOLUBLE TNF IN DIET-INDUCED PERIPHERAL AND CENTRAL INFLAMMATION IN A MOUSE MODEL OF ALZHEIMER’S DISEASE
Poster Presentations: Monday, July 17, 2017
large standardized dominance weights for IL-17a, interferongamma, IL-l2, and VEGF in CSF, as well IL-4 in serum. Conclusions: Inflammatory proteins have been widely documented in the AD brain. The results of the current study suggest that changes in BBB function resulting in altered permeability and transport are related to expression of specific inflammatory proteins, and that the shifting distribution of these proteins from serum to CSF in AD and MCI is correlated with more severe perturbations in BBB function.
P2-090
ROLE OF SOLUBLE TNF IN DIET-INDUCED PERIPHERAL AND CENTRAL INFLAMMATION IN A MOUSE MODEL OF ALZHEIMER’S DISEASE
Malu G. Tansey, Kathryn P. MacPherson, Lori N. Eidson, Mary K. Herrick, Maria Elizabeth de Sousa Rodrigues, Danielle Oliver, Sean D. Kelly, Yuan Yang, Jianjun Chang, Lindsey Sniffen, Emory University School of Medicine, Atlanta, GA, USA. Contact e-mail: [email protected] Background: Obesity and hypertension contribute to increased
risk for neurodegenerative diseases, including Alzheimer’s disease (AD). Peripheral inflammation, induced by unhealthy diet influences brain function, increases blood brain barrier (BBB) permeability, and induces brain inflammation. However, the exact mechanism by which chronic peripheral inflammation impacts AD-like pathology is unknown. Elevated levels of TNF in the CSF and plasma have been reported in AD patients. TNF promotes brain inflammation, increased BBB permeability, and altered regulation of immune cell trafficking. Here we tested the hypothesis that soluble TNF mediates the effects of an obesogenic diet on AD-like pathology and peripheral immune cell traffic to the CNS. Methods: We fed 5xFAD (Tg) mice a diet high in fructose and fat (HFHF) or a control diet (CD) for 2 months to induce low grade-chronic peripheral inflammation. After one month, we inhibited peripheral and central soluble TNF signaling with the BBB-permeant peptide XPro1595, and assessed immune cell populations in the brain and blood via flow cytometry, inflammatory gene expression (qPCR), and microglia activation and amyloid (IHC) in AD-relevant brain regions. Results: We found that diet impacts immune populations in the blood and brain. Within the blood Tg mice had increased frequency of CD11b+ monocytes; within this population Ly6Clo monocytes were increased, while MHCII+ monocytes were decreased. Four weeks of HFHF diet decreased the frequency of CD4+ T cells within the blood of Tg mice as compared to non-Tg CD mice. Following 8 weeks of HFHF diet, the frequency of CD45hiLy6ChiCD11b+ cells in the brain of Tg mice was reduced while the frequency of CD8+ T cells was increased as compared to non-Tg mice. Analysis of inflammation-related gene expression in the CNS is underway for correlation with changes in central and peripheral immunophenotypes. An additional cohort of mice is being treated with XPro1595 to investigate the hypothesis that inhibition of soluble TNF can mitigate diet-induced alterations in immune cell profiles centrally and peripherally and delay AD-like pathology. Conclusions: An obesogenic diet alters innate and adaptive immune cell populations in the blood and brain of 5xFAD mice and may promote neuroinflammation which may in turn accelerate AD-like pathology.
P2-091
P641
LEAD DESIGN FOR CLASSICAL AUTOIMMUNE REACTION OF NEUROMYELITIS OPTICA SPECTRUM DISORDERS
Meng Hao1, Pan Chenling2, Wan Qun3, Zhao Yong4, Jun Xu5, 1Northern Jiangsu People’s Hospital, Yangzhou, China; 2Kunming University of Science and Technology, Kunming, China; 3Nanjing Agricultural University, Nanjing, China; 4Beijing Computing Center, Beijing, China; 5 Subei People’s Hospital, Yangzhou, China. Contact e-mail: howardmen@ outlook.com
large standardized dominance weights for IL-17a, interferongamma, IL-l2, and VEGF in CSF, as well IL-4 in serum. Conclusions: Inflammatory proteins have been widely documented in the AD brain. The results of the current study suggest that changes in BBB function resulting in altered permeability and transport are related to expression of specific inflammatory proteins, and that the shifting distribution of these proteins from serum to CSF in AD and MCI is correlated with more severe perturbations in BBB function.
P2-090
ROLE OF SOLUBLE TNF IN DIET-INDUCED PERIPHERAL AND CENTRAL INFLAMMATION IN A MOUSE MODEL OF ALZHEIMER’S DISEASE
Malu G. Tansey, Kathryn P. MacPherson, Lori N. Eidson, Mary K. Herrick, Maria Elizabeth de Sousa Rodrigues, Danielle Oliver, Sean D. Kelly, Yuan Yang, Jianjun Chang, Lindsey Sniffen, Emory University School of Medicine, Atlanta, GA, USA. Contact e-mail: [email protected] Background: Obesity and hypertension contribute to increased
risk for neurodegenerative diseases, including Alzheimer’s disease (AD). Peripheral inflammation, induced by unhealthy diet influences brain function, increases blood brain barrier (BBB) permeability, and induces brain inflammation. However, the exact mechanism by which chronic peripheral inflammation impacts AD-like pathology is unknown. Elevated levels of TNF in the CSF and plasma have been reported in AD patients. TNF promotes brain inflammation, increased BBB permeability, and altered regulation of immune cell trafficking. Here we tested the hypothesis that soluble TNF mediates the effects of an obesogenic diet on AD-like pathology and peripheral immune cell traffic to the CNS. Methods: We fed 5xFAD (Tg) mice a diet high in fructose and fat (HFHF) or a control diet (CD) for 2 months to induce low grade-chronic peripheral inflammation. After one month, we inhibited peripheral and central soluble TNF signaling with the BBB-permeant peptide XPro1595, and assessed immune cell populations in the brain and blood via flow cytometry, inflammatory gene expression (qPCR), and microglia activation and amyloid (IHC) in AD-relevant brain regions. Results: We found that diet impacts immune populations in the blood and brain. Within the blood Tg mice had increased frequency of CD11b+ monocytes; within this population Ly6Clo monocytes were increased, while MHCII+ monocytes were decreased. Four weeks of HFHF diet decreased the frequency of CD4+ T cells within the blood of Tg mice as compared to non-Tg CD mice. Following 8 weeks of HFHF diet, the frequency of CD45hiLy6ChiCD11b+ cells in the brain of Tg mice was reduced while the frequency of CD8+ T cells was increased as compared to non-Tg mice. Analysis of inflammation-related gene expression in the CNS is underway for correlation with changes in central and peripheral immunophenotypes. An additional cohort of mice is being treated with XPro1595 to investigate the hypothesis that inhibition of soluble TNF can mitigate diet-induced alterations in immune cell profiles centrally and peripherally and delay AD-like pathology. Conclusions: An obesogenic diet alters innate and adaptive immune cell populations in the blood and brain of 5xFAD mice and may promote neuroinflammation which may in turn accelerate AD-like pathology.
P2-091
P641
LEAD DESIGN FOR CLASSICAL AUTOIMMUNE REACTION OF NEUROMYELITIS OPTICA SPECTRUM DISORDERS
Meng Hao1, Pan Chenling2, Wan Qun3, Zhao Yong4, Jun Xu5, 1Northern Jiangsu People’s Hospital, Yangzhou, China; 2Kunming University of Science and Technology, Kunming, China; 3Nanjing Agricultural University, Nanjing, China; 4Beijing Computing Center, Beijing, China; 5 Subei People’s Hospital, Yangzhou, China. Contact e-mail: howardmen@ outlook.com