| First Author | López-Gambero AJ | Year | 2021 |
| Journal | Int J Mol Sci | Volume | 22 |
| Issue | 10 | PubMed ID | 34065168 |
| Mgi Jnum | J:311252 | Mgi Id | MGI:6752682 |
| Doi | 10.3390/ijms22105365 | Citation | Lopez-Gambero AJ, et al. (2021) A Negative Energy Balance Is Associated with Metabolic Dysfunctions in the Hypothalamus of a Humanized Preclinical Model of Alzheimer's Disease, the 5XFAD Mouse. Int J Mol Sci 22(10) |
| abstractText | Increasing evidence links metabolic disorders with neurodegenerative processes including Alzheimer's disease (AD). Late AD is associated with amyloid (Abeta) 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 (Tg(5xFAD/5xFAD)), heterozygous (Tg(5xFAD/-)), and non-transgenic (Non-Tg) littermates. Although histological analysis showed absence of Abeta plaques in the hypothalamus of 5xFAD mice, this brain region displayed increased protein levels of GFAP and IBA1 in both Tg(5xFAD/-) and Tg(5xFAD/5xFAD) mice and increased expression of IL-1beta in Tg(5xFAD/5xFAD) mice, suggesting neuroinflammation. This condition was accompanied by decreased body weight, food intake, and energy expenditure in both Tg(5xFAD/-) and Tg(5xFAD/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. |
