👤 Ignacy Misztal

Aging is associated with disturbances in brain energy metabolism, mitochondrial dysfunction, and increased oxidative stress, all of which increase neuronal vulnerability and contribute to the development of neurodegenerative disorders. Growing evidence indicates that physical exercise exerts neuroprotective effects through the release of exerkines-exercise-induced signaling molecules that mediate communication between peripheral tissues and the brain. Among them, irisin, a proteolytic cleavage product of the membrane protein FNDC5, has emerged as an important mediator of the muscle-brain axis. This review summarizes current knowledge on the molecular mechanisms underlying irisin activity in the central nervous system, with particular emphasis on the AMPK-PGC-1α-FNDC5/BDNF signaling axis, rapid receptor-mediated pathways involving the cAMP/PKA/CREB and ERK/CREB cascades, and the regulation of mitochondrial homeostasis, including biogenesis, dynamics, autophagy, and mitophagy. Experimental studies suggest that irisin may improve neuroplasticity, neuronal survival, mitochondrial function, and reduce oxidative stress, thereby alleviating cognitive deficits in models of aging and neurodegeneration. Although the precise receptor mechanisms and intracellular signaling events remain incompletely understood, accumulating evidence identifies irisin as a promising therapeutic target linking metabolic adaptation with neuroprotection. Further investigation of irisin-dependent pathways may facilitate the development of novel strategies aimed at preserving brain function and delaying the progression of age-related neurodegenerative diseases. Show less

The purpose of this study was to identify genomic regions associated with carcass traits in an experimental Nelore cattle population. The studied data set contained 2,306 ultrasound records for longissimus muscle area (LMA), 1,832 for backfat thickness (BF), and 1,830 for rump fat thickness (RF). A high-density SNP panel (BovineHD BeadChip assay 700k, Illumina Inc., San Diego, CA) was used for genotyping. After genomic data quality control, 437,197 SNPs from 761 animals were available, of which 721 had phenotypes for LMA, 669 for BF, and 718 for RF. The SNP solutions were estimated using a single-step genomic BLUP approach (ssGWAS), which calculated the variance for windows of 50 consecutive SNPs and the regions that accounted for more than 0.5% of the additive genetic variance were used to search for candidate genes. The results indicated that 12, 18, and 15 different windows were associated to LMA, BF, and RF, respectively. Confirming the polygenic nature of the studied traits, 43, 65, and 53 genes were found in those associated windows, respectively for LMA, BF, and RF. Among the candidate genes, some of them, which already had their functions associated with the expression of energy metabolism, were found associated with fat deposition in this study. In addition, ALKBH3 and HSD17B12 genes, which are related in fibroblast death and metabolism of steroids, were found associated with LMA. The results presented here should help to better understand the genetic and physiologic mechanism regulating the muscle tissue deposition and subcutaneous fat cover expression of Zebu animals. The identification of candidate genes should contribute for Zebu breeding programs in order to consider carcass traits as selection criteria in their genetic evaluation. Show less

Nuclear localization of β-catenin is a hallmark of canonical Wnt signaling, a pathway that plays a crucial role in brain development and the neurogenesis of the adult brain. We recently showed that β-catenin accumulates specifically in mature thalamic neurons, where it regulates the expression of the Ca(v)3.1 voltage-gated calcium channel gene. Here, we investigated the mechanisms underlying β-catenin accumulation in thalamic neurons. We report that a lack of soluble factors produced either by glia or cortical neurons does not impair nuclear β-catenin accumulation in thalamic neurons. We next found that the number of thalamic neurons with β-catenin nuclear localization did not change when the Wnt/Dishevelled signaling pathway was inhibited by Dickkopf1 or a dominant negative mutant of Dishevelled3. These results suggest a WNT-independent cell-autonomous mechanism. We found that the protein levels of APC, AXIN1, and GSK3β, components of the β-catenin degradation complex, were lower in the thalamus than in the cortex of the adult rat brain. Reduced levels of these proteins were also observed in cultured thalamic neurons compared with cortical cultures. Finally, pulse-chase experiments confirmed that cytoplasmic β-catenin turnover was slower in thalamic neurons than in cortical neurons. Altogether, our data indicate that the nuclear localization of β-catenin in thalamic neurons is their cell-intrinsic feature, which was WNT-independent but associated with low levels of proteins involved in β-catenin labeling for ubiquitination and subsequent degradation. Show less