Pro-inflammatory interleukin-6 signaling links cognitive impairments and peripheral metabolic alterations in Alzheimer’s disease
| Autor: | Tharick A. Pascoal, Julyanna A. Peny, Elisa de Paula França Resende, Érica Leandro Marciano Vieira, Natalia M. Lyra e Silva, Isadora C. Furigo, Julia R. Clarke, Ricardo A.S. Lima-Filho, Antônio Lúcio Teixeira, Beatriz M. Longo, Pedro Rosa-Neto, Debora Hashiguchi, Jose Donato, Juliana T.S. Fortuna, Vivian S. Miya-Coreixas, Paulo Caramelli, Paul E. Fraser, Fernanda G. De Felice, Rafaella Araujo Gonçalves, Leonardo Cruz de Souza, Jose F. Abisambra, Sergio T. Ferreira |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty Hippocampus Inflammation Diseases Plaque Amyloid Neurosciences. Biological psychiatry. Neuropsychiatry Hippocampal formation Molecular neuroscience Article 03 medical and health sciences Cellular and Molecular Neuroscience Mice 0302 clinical medicine Alzheimer Disease Internal medicine medicine Memory impairment Animals Humans Cognitive Dysfunction SOCS3 Interleukin 6 STAT3 Biological Psychiatry Amyloid beta-Peptides biology business.industry Interleukin-6 MEMÓRIA ANIMAL Hyperintensity Psychiatry and Mental health 030104 developmental biology Endocrinology biology.protein medicine.symptom business 030217 neurology & neurosurgery RC321-571 |
| Zdroj: | Translational Psychiatry, Vol 11, Iss 1, Pp 1-15 (2021) Repositório Institucional da USP (Biblioteca Digital da Produção Intelectual) Universidade de São Paulo (USP) instacron:USP Translational Psychiatry |
| ISSN: | 2158-3188 |
| Popis: | Alzheimer’s disease (AD) is associated with memory impairment and altered peripheral metabolism. Mounting evidence indicates that abnormal signaling in a brain-periphery metabolic axis plays a role in AD pathophysiology. The activation of pro-inflammatory pathways in the brain, including the interleukin-6 (IL-6) pathway, comprises a potential point of convergence between memory dysfunction and metabolic alterations in AD that remains to be better explored. Using T2-weighted magnetic resonance imaging (MRI), we observed signs of probable inflammation in the hypothalamus and in the hippocampus of AD patients when compared to cognitively healthy control subjects. Pathological examination of post-mortem AD hypothalamus revealed the presence of hyperphosphorylated tau and tangle-like structures, as well as parenchymal and vascular amyloid deposits surrounded by astrocytes. T2 hyperintensities on MRI positively correlated with plasma IL-6, and both correlated inversely with cognitive performance and hypothalamic/hippocampal volumes in AD patients. Increased IL-6 and suppressor of cytokine signaling 3 (SOCS3) were observed in post-mortem AD brains. Moreover, activation of the IL-6 pathway was observed in the hypothalamus and hippocampus of AD mice. Neutralization of IL-6 and inhibition of the signal transducer and activator of transcription 3 (STAT3) signaling in the brains of AD mouse models alleviated memory impairment and peripheral glucose intolerance, and normalized plasma IL-6 levels. Collectively, these results point to IL-6 as a link between cognitive impairment and peripheral metabolic alterations in AD. Targeting pro-inflammatory IL-6 signaling may be a strategy to alleviate memory impairment and metabolic alterations in the disease. |
| Databáze: | OpenAIRE |
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