Qiu S et al. · Jul 1, 2026
Hearing impairment is attributed to factors such as age, genetic predisposition, and environmental influences, among which environmental factors are considered modifiable. Among various environmental factors, the role of poor lifestyle habits is particularly critical, yet the specific mechanisms by which they contribute to hearing damage remain unclear. This study reveals that dysregulated hormone levels due to disrupted light exposure may significantly increase susceptibility to sensorineural hearing loss. In mice, circadian rhythm disruption was found to reduce melatonin and elevate serotonin levels in the inner ear, thereby increasing vulnerability to cisplatin-induced ototoxicity. In both in vivo and in vitro cisplatin-treatment models, we showed that combined treatment with melatonin protected hearing, reduced inner ear cell death, and preserved synaptic connections, whereas serotonin co-administration exacerbated the damage. Using small molecule-protein interaction prediction, we identified NOS3 as a potential target of both melatonin and serotonin, through which they appear to regulate the NO signaling pathway and influence hair cell ferroptosis. Finally, exogenous supplementation of NOS3 in cochlear tissues effectively mitigated cisplatin-induced hair cell damage, even under conditions of circadian rhythm disruption. These findings indicate that the melatonin/serotonin balance modulates susceptibility to sensorineural hearing loss via the NOS3-NO signaling pathway.
Neuroscience
He W et al. · Jul 1, 2026
Underage drinking has become a global public health concern. One of the major causes of underage drinking is stress. The orexin system has been reported to be involved in both alcohol addiction and stress. However, few studies have examined this system, especially among adolescents. Therefore, we constructed protein-protein interaction (PPI) networks to confirm that orexin receptors are connected to stress- and alcohol dependence-related genes, providing a theoretical basis for our experimental approach. Animal experiments employed the conditioned place preference (CPP), the foot-shock stress model and the enzyme-linked immunosorbent assay (ELISA), to elucidate the role of the orexin system in the stress-induced alcohol addiction-related behaviour among adolescent mice. Our results revealed that there were interactions among orexin system, chronic/acute stress and alcohol dependence related proteins. Otherwise, chronic stress can increase the animals' vulnerability to alcohol addition-related behaviour. Additionally, acute foot-shock can promote alcohol-seeking behaviour reinstatement and facilitate orexin concentrations in brain regions that have been shown to be associated with reward and addiction. Moreover, the inhibition of orexin receptors can attenuate the formation and reinstatement of alcohol addiction-like behaviour among adolescent mice. Collectively, our findings indicate that orexin system may be a pivotal target for preventing stress-induced alcohol addiction and reinstatement among the adolescents.
Neuroscience
Chen C et al. · Jul 1, 2026
Cardiomyocyte senescence drives cardiovascular disease, underscoring the need to define its molecular mechanisms. The role of cystic fibrosis transmembrane conductance regulator (CFTR) ion channel in this process remains unclear, particularly regarding its expression and function. Atrial tissues were collected from patients with sinus rhythm or atrial fibrillation (AF) of varying durations. CFTR was downregulated in AF patients and negatively correlated with p16, p21, and p53. Myocardial aging models were established using D-galactose (D-gal) in both mice and neonatal mouse cardiomyocytes (CMs). In both animal and cellular models, D-gal increased SA-β-gal positivity and senescence markers while decreasing CFTR. Overexpressing CFTR reduced D-gal-induced elevations in p16, p21, p53, and malondialdehyde (MDA), and restored superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (CAT) activities. Mechanistically, CFTR alleviates mitochondrial oxidative stress damage by enhancing plasma membrane Ca 2+ ATPase (PMCA) activity to reduce cytoplasmic Ca 2+ levels. Furthermore, we identified USP45 as a direct binding partner of CFTR, which deubiquitinates CFTR by specifically targeting K48-linked chains and the K688 residue. CFTR knockdown exacerbated D-gal-induced senescence and mitochondrial oxidative stress, which was rescued by USP45 overexpression. In conclusion, this study reveals a novel mechanism in which USP45-mediated deubiquitination of CFTR mitigates cardiomyocyte senescence and mitochondrial oxidative stress, offering a targeted intervention against age-related cardiovascular diseases.
Neuroscience
Deady C et al. · Jul 1, 2026
Prenatal stress is associated with deleterious neurodevelopmental consequences in affected offspring. Prenatal stress via exposure to high physiological levels of inflammation in utero may induce an inflammatory state in the fetal brain. However, inflammation is not only associated with disease-states but also can be seen in a healthy pregnancy. There is limited research examining the potential that exposure to biological mediators of stress may have on neurodevelopment. We aim to determine whether certain circulating biological markers in maternal serum influence neurite growth in partially differentiated SH-SY5Y cells as a potential mechanism impacting neurodevelopment. Blood was collected at 20-weeks' gestation as part of the SCOPE pregnancy cohort study. These factors, including pro-inflammatory cytokines, markers of tryptophan metabolism, and gut permeability that were previously analysed, were used to stratify women into low (n = 10) and high (n = 10) biological stress groups. Exposure to the serum categorised as 'high-stress' significantly reduced neurite length in comparison to serum categorised as 'low-stress', with tumour necrosis factor-α playing a substantial role in mediating this reduction. The 'high-stress' serum was subsequently found to increase the levels of phospho-Ser536-p65. Phosphorylation of p65 Ser536 has previously been shown to switch NF-κΒ from promoting neuronal growth, to inhibiting it. The reduction in neurite length seen following exposure to the 'high-stress' serum was prevented when NF-κΒ p65 was knocked down. The present study emphasises the potential negative impact that circulating factors may have on neuronal growth, and the mechanism behind it.
Neuroscience
Augusto AGB et al. · Jul 1, 2026
Excessive intake of saturated fats triggers inflammation in the hypothalamus, a key regulator of energy balance. In the chronic phase of this inflammatory response, bone marrow-derived and lymphoid cells are chemoattracted to this region, partially mitigating high-fat diet (HFD)-induced metabolic impairments. In rodents, the onset and magnitude of this inflammation differ between males and females, reflecting sex-specific patterns of metabolic regulation. However, how the hypothalamic chemokine profile evolves during HFD-induced inflammation, and whether it is influenced by biological sex, remains unclear. Here, male and female C57BL/6J mice were fed a HFD for 1, 3, 14, or 28 days. To isolate the role of ovarian hormones in modulating hypothalamic chemokine profile, we also analyzed ovariectomized (OVX) females with or without estrogen replacement. Quantitative polymerase chain reaction-based expression analysis revealed that most chemokines and their receptors were transiently modulated in the hypothalamus during the course of the HFD exposure, showing reduced levels in the acute phase and normalization during the chronic phase. Despite the modest sex-dependent effects observed, messenger RNA expression of the chemokine receptor C-X-C motif chemokine receptor 3 (CXCR3) was significantly higher in females than in males after 14 and 28 days of HFD, suggesting faster recruitment of CXCR3 + immune cells that may contribute to female protection against metabolic dysfunction. Females lacking ovarian hormone production displayed increased hypothalamic expression of Cxcr3 and Ccl2. Only Cxcr3 expression was partially normalized by estradiol treatment, suggesting that non-estrogenic ovarian factors may play a role in modulating specific chemokine signaling pathways. Together, our findings show that hypothalamic chemokine signaling is dynamically and transiently regulated throughout the phases of HFD-induced inflammation, with Cxcr3 modulation by HFD and ovarian hormones contributing to sex-specific resilience against metabolic inflammation.
Neuroscience
Vogelsang DA et al. · Jul 1, 2026
Studies in animals have robustly shown that exposure to novelty can promote memory for information presented in the temporal vicinity. In humans, however, evidence for such novelty-related memory benefits has been mixed. In this EEG study, we investigated the neurobiological mechanisms underlying effects of novelty on memory and whether individual differences in exploration patterns help explain these inconsistencies. We examined the role of theta oscillations in exploring a novel or familiar environment as well as whether spatial exploration behavior can modulate the beneficial effects of novelty on memory. Participants first explored one of two virtual environments and subsequently explored the same (familiar condition) or a new environment (novel condition). After exploring novel and familiar environments, participants performed a word learning task followed by a free recall and recognition memory test. Neurologically, exploration of the familiar rather than novel environment increased theta power, which may reflect environment-related memory processes. However, we did not observe any differences in theta power associated with successful encoding of words after exploring a novel versus familiar environment. Behaviorally, no main effect of novelty on free recall was observed. Crucially, when accounting for variance in spatial exploration patterns, words encoded after exploring a novel environment were recalled better than words encoded after exploring a familiar environment. Furthermore, an interaction effect between the condition and exploratory behavior revealed that increased exploration benefitted free recall specifically in the familiar condition. These findings emphasize the importance of considering the way in which individuals explore a virtual environment when examining novelty effects on memory.
Neuroscience
Tang YJ et al. · Jul 1, 2026
Background Sepsis-induced acute kidney injury (S-AKI) is a major global public health concern, yet effective therapeutic strategies remain limited. Mitochondrial dysfunction in renal tissues is a key pathogenic mechanism underlying S-AKI. GTS-21, a selective α7 nicotinic acetylcholine receptor (α7nAChR) agonist, exhibits anti-inflammatory and renoprotective effects in S-AKI. Methods We investigated the role of α7nAChR in S-AKI using both in vitro (lipopolysaccharide (LPS)-induced renal tubular cell injury) and in vivo (caecal ligation and puncture (CLP)-induced septic mice) models, with GTS-21 treatment. Results GTS-21 significantly attenuated mitochondrial dysfunction, suppressed apoptosis, and alleviated inflammation, thereby protecting renal tubular cells and renal tissues against LPS- and CLP-induced injury. Mechanistically, GTS-21 activated α7nAChR and upregulated myocyte enhancer factor 2 (MEF2), peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), and heme oxygenase-1 (HO-1), which collectively mediate its anti-oxidative, anti-apoptotic and anti-inflammatory effects. Conclusion These findings suggest that GTS-21 may represent a potential therapeutic strategy for sepsis-induced kidney injury.
Neuroscience