In humans and mice, Nkx2-1 and Pax8 are crucial morphogenic transcription factors defining the early development of the thyroid and specific extrathyroidal tissues. By using 3-month-old single or double heterozygotes for Nkx2-1- and Pax8-null mutations (DHTP) mice, we studied brain abnormalities under different human-like dysthyroidisms, focusing on putative alterations of specific neurotransmitter systems, expression of markers of pre- and post-synaptic function and, given the physio-pathological role mitochondria have in controlling the bioenergetic status of neurons, of mitochondrial dynamics and oxidative balance. Compared to Wt controls, DHTP mice, bearing both systemic and brain hypothyroidism, showed altered expression of synaptic markers, generic and cholinergic (corroborated by immunohistochemistry in caudate, putamen, hippocampus, and basal forebrain) and glutamatergic ones, and reduced expression of key proteins of synaptic plasticity potency and several isoforms of glutamate receptors. The brain of DHTP mice was characterized by lower levels of H2O2 and imbalanced mitochondrial dynamics. Nkx2-1 + / - mice showed dopaminergic neuron-specific alterations, morphologically, more evident in the substantia nigra of DHTP mice. Nkx2-1 + / - mice also showed enhanced mitochondrial biogenesis and oxidative capacity likely as a global response of the brain to Nkx2-1 haploinsufficiency and/or to their elevated T3 circulating levels. Reduced transcription of both tyrosine hydroxylase and dopamine transporter was observed in Pax8 + / - euthyroid mice, suggesting a dopaminergic dysfunction, albeit likely at an early stage, but consistent with the deregulated glucose homeostasis observed in such animals. Overall, new information was obtained on the impact of haploinsufficiency of Pax8 and NKx2-1 on several brain neuroanatomical, molecular, and neurochemical aspects, thus opening the way for future targeting brain dysfunctions in the management of both overt and subclinical thyroid dysfunctions.
© 2024. The Author(s).

Land-use change may drive viral spillover from bats into humans, partly through dietary shifts caused by decreased availability of native foods and increased availability of cultivated foods. We experimentally manipulated diets of Jamaican fruit bats to investigate whether diet influences viral shedding. To reflect dietary changes experienced by wild bats during periods of nutritional stress, Jamaican fruit bats were fed either a standard diet or a putative suboptimal diet, which was deprived of protein (suboptimal-sugar diet) and/or supplemented with fat (suboptimal-fat diet). Upon H18N11 influenza A-virus infection, bats fed on the suboptimal-sugar diet shed the most viral RNA for the longest period, but bats fed the suboptimal-fat diet shed the least viral RNA for the shortest period. Bats on both suboptimal diets ate more food than the standard diet, suggesting nutritional changes may alter foraging behaviour. This study serves as an initial step in understanding whether and how dietary shifts may influence viral dynamics in bats, which alters the risk of spillover to humans.

Methylsulfonylmethane (MSM) is a sulfur-containing molecule with reported anti-inflammatory and antioxidant activities. Exercise causes the formation of free radicals and stimulates inflammatory gene expression in leukocytes and skeletal muscle. The hypothesis that dietary supplementation with MSM alters the exercise-mediated inflammatory and oxidant response was assessed in unfit adult thoroughbred geldings. Ten geldings (6.7 ± 1.6 yr) were assigned to a diet supplemented without (CON, n = 5) or with 21 g of MSM (n = 5) for 30 days. Following the supplementation period, horses performed a standardized exercise test (SET) with blood collections before (t = 0), 10 min, 1 h, 4 h, and 24 h post-SET. Skeletal muscle biopsies were retrieved from the middle gluteus before and 1 h post-SET for total RNA isolation. All horses were rested for 120 days before the experiment was repeated in a cross-over design. Plasma total antioxidant capacity was unaffected (p > 0.05) by either exercise or MSM. Plasma glutathione peroxidase activity was less (p < 0.05) in MSM horses than in the CON. Plasma IL6, IL8, IL10, and TNFα were unaffected (p > 0.05) by either exercise or diet. Transcriptomic analysis of skeletal muscle revealed 35 genes were differentially expressed (DEG; p < 0.05) by 2-fold or more in response to exercise; no MSM DEGs were noted. A comparison of the exercise by diet contrasts revealed that horses supplemented with MSM contained a greater number of exercise-responsive genes (630; logFC > 0.2; q < 0.05) by comparison to the CON (237), with many of these mapping to the immune response (71) and cytokine signal transduction (60) pathways. These results suggest supplementation of MSM as a dietary aid for improved anti-inflammatory responses in skeletal muscle following exercise.

Traumatic spinal cord injury (SCI) is a serious medical condition that places patients at high risk of developing gastric ulceration and gastrointestinal bleeding. One preventative strategy involves the use of omeprazole; however, its chronic use is associated with adverse effects, highlighting the need for alternative therapies. This study evaluated the protective effects of methyl eugenol (ME) on gastric mucosal damage in a rat model of SCI. ME was administered orally at doses of 30, 100, and 177 mg/kg in SCI induced at the T9 level, alongside diclofenac or ketorolac (30 mg/kg each). The enzymatic activity of superoxide dismutase, catalase, and glutathione peroxidase was assessed, and the levels of total glutathione and malondialdehyde were determined using biochemical kits. Additionally, stomach histological sections were analyzed. ME exhibited dose-dependent gastroprotective effects, with maximal protection observed at 177 mg/kg in the presence of diclofenac (9.78 ± 2.16 mm2) or ketorolac (12.49 ± 2.17 mm2). A histological analysis confirmed these findings. In conclusion, methyl eugenol protects the gastric mucosa from SCI-induced damage, with glutathione peroxidase and catalase playing key roles in its mechanism of gastroprotection.

Polyphenols have antioxidant and anti-inflammatory properties and maintain the immune system in balance; therefore, the aim of the study was to investigate the effect of polyphenols present in pomegranate peel extract on the spleens of rats with metabolic syndrome. The study objects were adult male Zucker Diabetic Fatty (ZDF-Leprfa/Crl, fa/fa) rats. The rats were divided into a control group (MetS) consisting of rats with metabolic syndrome and four study groups consisting of rats with metabolic syndrome (MetS + 100 mg and MetS + 200 mg) or healthy animals (H + 100 mg and H + 200 mg) receiving polyphenol extract at a dose of 100 mg or 200 mg/kg, respectively. Concentrations of IL-6, NF-κB, NFATc1, Cyt-C, TNFα, MMP-2, ROS/RNS, and MDA were measured; the activities of GPX, SOD, CAT, MMP-2, and MMP-9 were assessed; and the expression of the BAX and BCL-2 genes was evaluated in homogenized spleens. In conclusion, pomegranate extract may lead to an increase in catalase and glutathione peroxidase activity. Additionally, it may have a reducing effect on the ROS/RNS level, leading to a reduction in the activity of SOD in the MetS groups with PPE administration. Moreover, the BCL-2 gene showed lower expression in the MetS + 100 mg group compared to the H + 100 mg group, indicating that the balance between pro- and antiapoptotic factors of the BCL-2 family may be disrupted by the metabolic syndrome promoting the proapoptotic pathway.