Early-life noise exposure causes cognitive impairment in a sex-dependent manner by disrupting homeostasis of the microbiota-gut-brain axis.

Epidemiological investigations show that noise exposure in early life is associated with health and cognitive impairment. The gut microbiome established in early life plays a crucial role in modulating developmental processes that subsequently affect brain function and behavior. Here, we examined the impact of early-life exposure to noise on cognitive function in adolescent rats by analyzing the gut microbiome and metabolome to elucidate the underlying mechanisms. Chronic noise exposure during early life led to cognitive deficits, hippocampal injury, and neuroinflammation. Early-life noise exposure showed significant difference on the composition and function of the gut microbiome throughout adolescence, subsequently causing axis-series changes in fecal short-chain fatty acid (SCFA) metabolism and serum metabolome profiles, as well as dysregulation of endothelial tight junction proteins, in both intestine and brain. We also observed sex-dependent effects of microbiota depletion on SCFA-related beneficial bacteria in adolescence. Experiments on microbiota transplantation and SCFA supplementation further confirmed the role of intestinal bacteria and related SCFAs in early-life noise-exposure-induced impairments in cognition, epithelial integrity, and neuroinflammation. Overall, these results highlight the homeostatic imbalance of microbiota-gut-brain axis as an important physiological response toward environmental noise during early life and reveals subtle differences in molecular signaling processes between male and female rats.

Lactobacillus rhamnosus GG ameliorates noise-induced cognitive deficits and systemic inflammation in rats by modulating the gut-brain axis.

Background: Environmental noise exposure is linked to neuroinflammation and imbalance of the gut microbiota. Promoting gut microbiota homeostasis may be a key factor in relieving the deleterious non-auditory effects of noise. This study aimed to investigate the effect of Lactobacillus rhamnosus GG (LGG) intervention on noise-induced cognitive deficits and systemic inflammation in rats. Methods: Learning and memory were assessed using the Morris water maze, while 16S rRNA sequencing and gas chromatography-mass spectrometry were used to analyze the gut microbiota and short-chain fatty acid (SCFA) content. Endothelial tight junction proteins and serum inflammatory mediators were assessed to explore the underlying pathological mechanisms. Results: The results indicated that Lactobacillus rhamnosus GG intervention ameliorated noise-induced memory deterioration, promoted the proliferation of beneficial bacteria, inhibited the growth of harmful bacteria, improved dysregulation of SCFA-producing bacteria, and regulated SCFA levels. Mechanistically, noise exposure led to a decrease in tight junction proteins in the gut and hippocampus and an increase in serum inflammatory mediators, which were significantly alleviated by Lactobacillus rhamnosus GG intervention. Conclusion: Taken together, Lactobacillus rhamnosus GG intervention reduced gut bacterial translocation, restored gut and blood-brain barrier functions, and improved gut bacterial balance in rats exposed to chronic noise, thereby protecting against cognitive deficits and systemic inflammation by modulating the gut-brain axis.

[Effects of GLAST gene knockout on phenotype and hearing in mice].

OBJECTIVE: To investigate the effects of glutamate aspartate transporter (GLAST)deletion on the normal auditory function of mice. METHODS: We hybridized GLAST+/- mice with C57BL/6J background and identified the genotypes of their offspring by agarose gel electrophoresis. 9-10-week-old mice were selected to detect the expression of GLAST protein in the cochlea by immunofluorescence staining and to verify the knockout results(n=3). The changes in weight from 7 days to 30 days after birth and the 30-day body length of male and female mice were compared(n=8). The auditory brainstem response(ABR) was used to detect the auditory threshold and the amplitude of wave I in 9-10-week-old male and female mice(n=5). RESULTS: Male GLAST-/- mice had shown significantly lower weight and body length compared to male GLAST+/+ and GLAST+/- mice(P＜0.01), and male GLAST-/- mice showed significant differences compared to GLAST+/+ from P7 to P30 statistical time. Male GLAST-/- mice exhibited a significant reduction in weight after P15 compared to male GLAST+/- mice. In contrast, no significant differences in weight and body length were observed in female GLAST-/- mice compared with female GLAST+/+ and GLAST+/- mice. There was no difference in the hearing threshold detected by ABR between the three genotypes in both male and female mice, but the amplitude of wave I in GLAST-/- mice was significantly lower than that in male GLAST+/+ mice(P＜0.01). In contrast, the amplitude of wave I in females was reduced throughout the stimulus intensity but was most significant only at high-intensity stimulation (e.g.80 dB, 90 dB) (P＜0.05). CONCLUSION: GLAST knockout affects the normal growth and development of male mice, and decreases the amplitude of wave I, but do not change the threshold, suggesting that GLAST knockout may lead to synaptic pathological changes, and there are gender differences in this effect.

Around-the-Clock Noise Induces AD-like Neuropathology by Disrupting Autophagy Flux Homeostasis.

Environmental noise is a common hazard in military operations. Military service members during long operations are often exposed to around-the-clock noise and suffer massive emotional and cognitive dysfunction related to an Alzheimer's disease (AD)-like neuropathology. It is essential to clarify the mechanisms underlying the effects of around-the-clock noise exposure on the central nervous system. Here, Wistar rats were continuously exposed to white noise (95 dB during the on-duty phase [8:00-16:00] and 75 dB during the off-duty phase (16:00-8:00 the next day)) for 40 days. The levels of phosphorylated tau, amyloid-ß (Aß), and neuroinflammation in the cortex and hippocampus were assessed and autophagosome (AP) aggregation was observed by transmission electron microscopy. Dyshomeostasis of autophagic flux resulting from around-the-clock noise exposure was assessed at different stages to investigate the potential pathological mechanisms. Around-the-clock noise significantly increased Aß peptide, tau phosphorylation at Ser396 and Ser404, and neuroinflammation. Moreover, the AMPK-mTOR signaling pathway was depressed in the cortex and the hippocampus of rats exposed to around-the-clock noise. Consequently, autophagosome-lysosome fusion was deterred and resulted in AP accumulation. Our results indicate that around-the-clock noise exposure has detrimental influences on autophagic flux homeostasis and may be associated with AD-like neuropathology in the cortex and the hippocampus.