Obesity in Aging Exacerbates Neuroinflammation, Dysregulating Synaptic Function-Related Genes and Altering Eicosanoid Synthesis in the Mouse Hippocampus: Potential Role in Impaired Synaptic Plasticity and Cognitive Decline

Marta Noa Valcarcel-Ares, Zsuzsanna Tucsek, Tamas Kiss, Cory B. Giles, Stefano Tarantini, Andriy Yabluchanskiy, Priya Balasubramanian, Tripti Gautam, Veronica Galvan, Praveen Ballabh, Arlan Richardson, Willard M. Freeman, Jonathan D. Wren, Ferenc Deak, Zoltan Ungvari, Anna Csiszar

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

There is strong evidence that obesity has deleterious effects on cognitive function of older adults. Previous preclinical studies demonstrate that obesity in aging is associated with a heightened state of systemic inflammation, which exacerbates blood-brain barrier disruption, promoting neuroinflammation and oxidative stress. To test the hypothesis that synergistic effects of obesity and aging on inflammatory processes exert deleterious effects on hippocampal function, young and aged C57BL/6 mice were rendered obese by chronic feeding of a high-fat diet followed by assessment of learning and memory function, measurement of hippocampal long-term potentiation (LTP), assessment of changes in hippocampal expression of genes relevant for synaptic function and determination of synaptic density. Because there is increasing evidence that altered production of lipid mediators modulate LTP, neuroinflammation and neurovascular coupling responses, the effects of obesity on hippocampal levels of relevant eicosanoid mediators were also assessed. We found that aging exacerbates obesity-induced microglia activation, which is associated with deficits in hippocampal-dependent learning and memory tests, impaired LTP, decreased synaptic density, and dysregulation of genes involved in regulation of synaptic plasticity. Obesity in aging also resulted in an altered hippocampal eicosanoid profile, including decreases in vasodilator and pro-LTP epoxy-eicosatrienoic acids (EETs). Collectively, our results taken together with previous findings suggest that obesity in aging promotes hippocampal inflammation, which in turn may contribute to synaptic dysfunction and cognitive impairment.

Original languageEnglish (US)
Pages (from-to)290-298
Number of pages9
JournalThe journals of gerontology. Series A, Biological sciences and medical sciences
Volume74
Issue number3
DOIs
StatePublished - Feb 15 2019

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Neuronal Plasticity
Eicosanoids
Hippocampus
Obesity
Long-Term Potentiation
Genes
Learning
Inflammation
Microglia
High Fat Diet
Cognitive Dysfunction
Blood-Brain Barrier
Vasodilator Agents
Inbred C57BL Mouse
Cognition
Oxidative Stress
Lipids
Gene Expression
Acids

Keywords

  • Inflammaging
  • Metabolic syndrome
  • Mild cognitive impairment
  • Vascular cognitive impairment
  • VCI

ASJC Scopus subject areas

  • Aging
  • Geriatrics and Gerontology

Cite this

Obesity in Aging Exacerbates Neuroinflammation, Dysregulating Synaptic Function-Related Genes and Altering Eicosanoid Synthesis in the Mouse Hippocampus : Potential Role in Impaired Synaptic Plasticity and Cognitive Decline. / Valcarcel-Ares, Marta Noa; Tucsek, Zsuzsanna; Kiss, Tamas; Giles, Cory B.; Tarantini, Stefano; Yabluchanskiy, Andriy; Balasubramanian, Priya; Gautam, Tripti; Galvan, Veronica; Ballabh, Praveen; Richardson, Arlan; Freeman, Willard M.; Wren, Jonathan D.; Deak, Ferenc; Ungvari, Zoltan; Csiszar, Anna.

In: The journals of gerontology. Series A, Biological sciences and medical sciences, Vol. 74, No. 3, 15.02.2019, p. 290-298.

Research output: Contribution to journalArticle

Valcarcel-Ares, MN, Tucsek, Z, Kiss, T, Giles, CB, Tarantini, S, Yabluchanskiy, A, Balasubramanian, P, Gautam, T, Galvan, V, Ballabh, P, Richardson, A, Freeman, WM, Wren, JD, Deak, F, Ungvari, Z & Csiszar, A 2019, 'Obesity in Aging Exacerbates Neuroinflammation, Dysregulating Synaptic Function-Related Genes and Altering Eicosanoid Synthesis in the Mouse Hippocampus: Potential Role in Impaired Synaptic Plasticity and Cognitive Decline', The journals of gerontology. Series A, Biological sciences and medical sciences, vol. 74, no. 3, pp. 290-298. https://doi.org/10.1093/gerona/gly127
Valcarcel-Ares, Marta Noa ; Tucsek, Zsuzsanna ; Kiss, Tamas ; Giles, Cory B. ; Tarantini, Stefano ; Yabluchanskiy, Andriy ; Balasubramanian, Priya ; Gautam, Tripti ; Galvan, Veronica ; Ballabh, Praveen ; Richardson, Arlan ; Freeman, Willard M. ; Wren, Jonathan D. ; Deak, Ferenc ; Ungvari, Zoltan ; Csiszar, Anna. / Obesity in Aging Exacerbates Neuroinflammation, Dysregulating Synaptic Function-Related Genes and Altering Eicosanoid Synthesis in the Mouse Hippocampus : Potential Role in Impaired Synaptic Plasticity and Cognitive Decline. In: The journals of gerontology. Series A, Biological sciences and medical sciences. 2019 ; Vol. 74, No. 3. pp. 290-298.
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