👤 T C Peixoto

Parkinson's disease (PD) remains a challenging disease for treatment, which is usually polypharmacological. In addition to motor symptoms, non-motor symptoms such as depression are present in approximately 40% of patients, contributing to the loss of quality of life. In the last two decades, a growing body of evidence has emerged regarding the involvement of the microbiota-gut-brain axis in both PD and depression. Fructooligosaccharides (FOS) and galactooligosaccharides (GOS) are prebiotic fibers that can be fermented by the gut microbiota, which produce metabolites called short-chain fatty acids (SCFAs), whose effects can contribute to improvement in neurodegenerative and psychiatric conditions. This study analyzed the effects of FOS and GOS administration in a rotenone-induced PD model and demonstrated a relief of motor symptoms and depressive-like behavior, followed by an increase of brain serotonin and its respective receptor (SERT). FOS and GOS treatment also led to an increase in SCFAs-producing gut bacteria with significantly higher levels of serum and brain butyrate. Furthermore, in the intestine, prebiotics reduced the accumulation of α-synuclein, decreased inflammation, and improved the expression of zonula occludens and occludin. FOS and GOS also attenuated the loss of dopaminergic neurons and reduced neuroinflammation by decreasing α-synuclein, IBA-1, GFAP, iNOS, p-NFkB, and IL1-β levels in the substantia nigra and prefrontal cortex. In addition, these prebiotics improved neuroplasticity by promoting the expression of butyrate receptors (GPR43 and GPR109), BDNF, p-CREB, and synaptic protein PSD-95. In conclusion, FOS and GOS administration attenuatted depressive-like behavior, neuroinflammation, and synaptic plasticity in Parkinson's disease by modulating butyrate-producing gut bacteria. Show less

Plants need to integrate internal and environmental signals to mount adequate stress responses. The NUCLEAR PORE COMPLEX (NPC) component HIGH EXPRESSION OF OSMOTICALLY RESPONSIVE GENES 1 (HOS1) is emerging as such an integrator, affecting responses to cold, heat, light, and salinity. Stress conditions often converge in a low-energy signal that activates SUCROSE NON-FERMENTING 1-RELATED KINASE 1 (SnRK1) to promote stress tolerance and survival. Here, we explored the role of HOS1 in the SnRK1-dependent response to low-energy stress in Arabidopsis thaliana, using darkness as a treatment and a combination of genetic, biochemical, and phenotypic assays. We show that the induction of starvation genes and plant tolerance to prolonged darkness are defective in the hos1 mutant. HOS1 interacts physically with the SnRK1α1 catalytic subunit in yeast two-hybrid assays and in planta, and the nuclear accumulation of SnRK1α1 is reduced in the hos1 mutant. Likewise, another NPC mutant, nup160, exhibits lower activation of starvation genes and decreased tolerance to prolonged darkness. Importantly, defects in low-energy responses in the hos1 background are rescued by fusing SnRK1α1 to a potent nuclear localization signal or by sugar supplementation during the dark treatment. Altogether, this work demonstrates the importance of HOS1 for the nuclear accumulation of SnRK1α1, which is key for plant tolerance to low-energy conditions. Show less

Maternal smoking is a risk factor for progeny obesity. We have previously shown, in a rat model of neonatal tobacco smoke exposure, a mild increase in food intake and a considerable increase in visceral adiposity in the adult offspring. Males also had secondary hyperthyroidism, while females had only higher T4. Since brown adipose tissue (BAT) hypofunction is related to obesity, here we tested the hypothesis that higher levels of thyroid hormones are not functional in BAT, suggesting a lower metabolic rate. We evaluated autonomic nerve activity in BAT and its function in adult rats that were exposed to tobacco smoke during lactation. At birth, litters were adjusted to 3 male and 3 female pups/litter. From postnatal day (PND) 3 to 21, Wistar lactating rats and their pups were divided into SE group, smoke-exposed in a cigarette smoking machine (4 times/day) and C group, exposed to filtered air. Offspring were sacrificed at PND180. Adult SE rats of both genders had lower interscapular BAT autonomic nervous system activity, with higher BAT mass but no change in morphology. BAT UCP1 and CPT1a protein levels were decreased in the SE groups of both genders. Male SE rats had lower β3-AR, TRα1, and TRβ1 expression while females showed lower PGC1α expression. BAT Dio2 mRNA and hypothalamic POMC and MC4R levels were similar between groups. Hypothalamic pAMPK level was higher in SE males and lower in SE females. Thus, neonatal cigarette smoke exposure induces lower BAT thermogenic capacity, which can be obesogenic at adulthood. Show less

Excess fat content in chickens has a negative impact on poultry production. The discovery of QTL associated with fat deposition in the carcass allows the identification of positional candidate genes (PCGs) that might regulate fat deposition and be useful for selection against excess fat content in chicken's carcass. This study aimed to estimate genomic heritability coefficients and to identify QTLs and PCGs for abdominal fat (ABF) and skin (SKIN) traits in a broiler chicken population, originated from the White Plymouth Rock and White Cornish breeds. ABF and SKIN are moderately heritable traits in our broiler population with estimates ranging from 0.23 to 0.33. Using a high density SNP panel (355,027 informative SNPs), we detected nine unique QTLs that were associated with these fat traits. Among these, four QTL were novel, while five have been previously reported in the literature. Thirteen PCGs were identified that might regulate fat deposition in these QTL regions: JDP2, PLCG1, HNF4A, FITM2, ADIPOR1, PTPN11, MVK, APOA1, APOA4, APOA5, ENSGALG00000000477, ENSGALG00000000483, and ENSGALG00000005043. We used sequence information from founder animals to detect 4843 SNPs in the 13 PCGs. Among those, two were classified as potentially deleterious and two as high impact SNPs. This study generated novel results that can contribute to a better understanding of fat deposition in chickens. The use of high density array of SNPs increases genome coverage and improves QTL resolution than would have been achieved with low density. The identified PCGs were involved in many biological processes that regulate lipid storage. The SNPs identified in the PCGs, especially those predicted as potentially deleterious and high impact, may affect fat deposition. Validation should be undertaken before using these SNPs for selection against carcass fat accumulation and to improve feed efficiency in broiler chicken production. Show less