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Canal, C.

Publications and source records attributed to Canal, C..

2 recordsLinked to original sources

Regular parental exercise before mating influences offspring lower adiposity associated to hypothalamic neurodevelopmental changes

Physical inactivity is highly prevalent worldwide and affects not only individual health but also the health of future generations. However, the impact of parental physical activity, limited to the pre-mating period, on offspring body weight and composition remains poorly understood. Using a voluntary wheel running approach in mice, we uncovered that post-weaning offspring body weight and composition changes are modulated by the combined effects of pre-mating parental exercise and parental age. Notably, during lactation, pre-mating parental exercise reduced offspring visceral and subcutaneous adiposity, shortened tibia length in female offspring, and influenced offspring transcriptomic profiles of the hypothalamus, the central region regulating body weight and energy balance. These results highlight that regular pre-mating parental exercise may induce offspring neurodevelopmental changes. Although pre-mating exercise minimally impacted the expression of lactation-related genes in maternal subcutaneous fat, as well as breastmilk nutritional composition and miRNA content, these modest miRNA changes may nonetheless influence offspring hypothalamic regulation. Together, these data provide a comprehensive understanding of how parental age and pre-mating exercise impact post-weaning offspring body weight and composition and offer deeper insights into how regular pre-mating parental exercise influences offspring physiology during lactation.

neuroscience↗

Effects of Interleukin-6 dysregulation in a mouse model of Alzheimer's disease: unraveling the complexity beyond amyloidosis

Interleukin-6 (IL-6) is a cytokine detected in the brains and peripheral fluids of both Alzheimers disease (AD) patients and mouse models, where it colocalizes with amyloid-beta (A{beta}) levels and amyloid plaques. Interestingly, IL-6 deficiency ameliorates cognitive deficits and attenuates hippocampal neuroinflammation, whereas astrocyte-targeted IL-6 signaling via its soluble receptor accentuates pathological features in AD mouse models. This finding suggests that central IL-6 overexpression may actively drive disease manifestations. However, because IL-6 also signals through its classical membrane-bound receptor pathway, the overall impact of central IL-6 on Alzheimers disease pathophysiology is still not fully elucidated. To explore the contribution of central IL-6 overexpression in modulating AD-related mortality, metabolic, behavioral and neuroinflammatory changes in the hippocampus and cortex, we crossed a transgenic mouse model (Tg2576) of A{beta}-driven amyloidosis with mice expressing IL-6 under the Glial Fibrillary Acidic Protein (GFAP) promoter, which predominantly targets astrocytes. Chronic IL-6 overexpression reduced inguinal white adiposity in both males and females and decreased body weight in females. Early behavioral alterations were also observed, along with increased cortical and hippocampal A{beta}42/A{beta}40 ratios and gliosis in aged Tg2576 female and male mice. Interestingly, chronic IL-6 overexpression also decreased cortical and hippocampal periplaque astrocytosis and microgliosis, suggesting a heterogeneous response of astrocytes and microglia to IL-6 overexpression within the primary regions affected by this pathology. Finally, cortical transcriptomic profiling in Tg2576 mice revealed widespread changes in immune, synaptic, and stress response pathways in response to chronic IL-6 overexpression, with cortical neuroinflammatory and neurotransmission-associated gene networks showing sex-dependent differences. Our findings emphasize that chronic central-targeted IL-6 overexpression shapes the cortical and hippocampal molecular landscape underlying amyloidosis in both male and female Tg2576 mice. Thereby, we propose IL-6 as a potential target for future AD therapeutic strategies.

neuroscience↗