%0 Journal Article
%A López-Gambero, Antonio J.
%A Rosell-Valle, Cristina
%A Medina-Vera, Dina
%A Navarro, Juan Antonio
%A Vargas, Antonio
%A Rivera, Patricia
%A Sanjuan, Carlos
%A Rodríguez de Fonseca, Fernando
%A Suárez, Juan
%T A Negative Energy Balance Is Associated with Metabolic Dysfunctions in the Hypothalamus of a Humanized Preclinical Model of Alzheimer's Disease, the 5XFAD Mouse
%D 2021
%@ 1661-6596
%U http://hdl.handle.net/10668/4486
%X Increasing evidence links metabolic disorders with neurodegenerative processes including Alzheimer's disease (AD). Late AD is associated with amyloid (Aβ) plaque accumulation, neuroinflammation, and central insulin resistance. Here, a humanized AD model, the 5xFAD mouse model, was used to further explore food intake, energy expenditure, neuroinflammation, and neuroendocrine signaling in the hypothalamus. Experiments were performed on 6-month-old male and female full transgenic (Tg5xFAD/5xFAD), heterozygous (Tg5xFAD/-), and non-transgenic (Non-Tg) littermates. Although histological analysis showed absence of Aβ plaques in the hypothalamus of 5xFAD mice, this brain region displayed increased protein levels of GFAP and IBA1 in both Tg5xFAD/- and Tg5xFAD/5xFAD mice and increased expression of IL-1β in Tg5xFAD/5xFAD mice, suggesting neuroinflammation. This condition was accompanied by decreased body weight, food intake, and energy expenditure in both Tg5xFAD/- and Tg5xFAD/5xFAD mice. Negative energy balance was associated with altered circulating levels of insulin, GLP-1, GIP, ghrelin, and resistin; decreased insulin and leptin hypothalamic signaling; dysregulation in main metabolic sensors (phosphorylated IRS1, STAT5, AMPK, mTOR, ERK2); and neuropeptides controlling energy balance (NPY, AgRP, orexin, MCH). These results suggest that glial activation and metabolic dysfunctions in the hypothalamus of a mouse model of AD likely result in negative energy balance, which may contribute to AD pathogenesis development.
%K Alzheimer’s disease
%K 5xFAD
%K Insulin signaling
%K Energy expenditure
%K Hypothalamus
%K Neuroinflammation
%K Ghrelin
%K Insulin resistance
%K Leptin
%K Orexin
%K Resistin
%K STAT5 transcription factor
%K Body weight
%K Gastric inhibitory polypeptide
%K Enfermedad de Alzheimer
%K Proteínas sustrato del receptor de insulina
%K Metabolismo energético
%K Hipotálamo
%K Enfermedades neuroinflamatorias
%K Ghrelina
%K Resistencia a la insulina
%K Leptina
%K Orexinas
%K Resistina
%K Factor de transcripción STAT5
%K Peso corporal
%K Polipéptido inhibidor gástrico
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