Xylene and its derivatives are known to be neurotoxic to the central nervous system of animals. Our previous work has shown that para-xylene (PX) can cause an increase in apoptotic cells and abnormal avoidance behavior in Xenopus laevis . However, the mechanism underlying the impact of PX on neuronal structural and functional plasticity is less clear. Here, we examined the effects of PX on neuronal development and plasticity in the developing optic tectum. We found that HuC/D-positive neurons were more vulnerable than SOX2-positive progenitor cells or BLBP-positive radial glial cells after exposure to PX at 1 mM for 48 h. The further measurement of postsynaptic receptors and synaptic vesicle proteins showed that the expression levels of GluA1 and GluA2, but not Rab3a and SNAP25, were significantly decreased in the tectal brain. In vivo time-lapse images and electrophysiological recordings showed that PX exposure resulted in significant deficits in neuronal structure, particularly in the total dendritic branch length (TDBL), and visual stimulation-induced excitatory compound synaptic currents (eCSCs) without altering neurotransmitter release probability. Strikingly, coexposure to d -glucuronolactone (GA) and PX rescued the structural and functional deficits caused by PX exposure alone. Furthermore, we found that visual experience-induced structural, functional and behavioral plasticity was blocked by PX exposure, which was also rescued by the simultaneous administration of GA and PX . Thus, our findings indicate that PX is neurotoxic to brain development and plasticity and that GA may be considered a promising candidate to treat PX-induced defects in neural circuits.
Wang Yujin,Jiang Hua,Wang Lijun,Gan Huiping,Xiao Xinchun,Huang Liangwu,Li Wenxin,Li Zongrun
Functional constipation (FC) is one of the most common gastrointestinal disorders characterized by hard stools and infrequent bowel movements, which is associated with dysfunction of the enteric nervous system and intestinal motility. Luteolin, a naturally occurring flavone, was reported to possess potential pharmacological activities on intestinal inflammation and nerve injury. This study aimed to explore the role of luteolin and its functional mechanism in loperamide-induced FC mice. Our results showed that luteolin treatment reversed the reduction in defecation frequency, fecal water content, and intestinal transit ratio, and the elevation in transit time of FC models. Consistently, luteolin increased the thickness of the muscular layer and lessened colonic histopathological injury induced by loperamide. Furthermore, we revealed that luteolin treatment increased the expression of neuronal protein HuC/D and the levels of intestinal motility-related biomarkers, including substance P (SP), vasoactive intestinal polypeptide (VIP), and acetylcholine (ACh), as well as interstitial cells of Cajal (ICC) biomarker KIT proto-oncogene, receptor tyrosine kinase (C-Kit), and anoctamin-1 (ANO1), implying that luteolin mediated enhancement of colonic function and contributed to the anti-intestinal dysmotility against loperamide-induced FC. Additionally, luteolin decreased the upregulation of aquaporin (AQP)-3, AQP-4, and AQP-8 in the colon of FC mice. In summary, our data showed that luteolin might be an attractive option for developing FC-relieving medications.
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