Acid-sensing ion channel 1A (ASIC1A) is abundant in the nucleus accumbens (NAc), a region known for its role in addiction. Because ASIC1A has been previously suggested to promote associative learning, we hypothesized that disrupting ASIC1A in the NAc would reduce drug-associated learning and memory. However, contrary to this hypothesis, we found that disrupting ASIC1A in the NAc increased cocaine-conditioned place preference, suggesting an unexpected role for ASIC1A in addiction-related behavior. Moreover, overexpressing ASIC1A in rat NAc reduced cocaine self-administration. Investigating the underlying mechanisms, we identified a novel postsynaptic current during neurotransmission mediated by ASIC1A and ASIC2 and thus well-positioned to regulate synapse structure and function. Consistent with this possibility, disrupting ASIC1A altered dendritic spine density and glutamate receptor function, and increased cocaine-evoked plasticity in AMPA-to-NMDA ratio, all resembling changes previously associated with cocaine-induced behavior. Together, these data suggest ASIC1A inhibits plasticity underlying addiction-related behavior, and raise the possibility of therapies for drug addiction by targeting ASIC-dependent neurotransmission.
Carbon dioxide (CO 2 ) inhalation lowers brain pH and induces anxiety, fear, and panic responses in humans. In mice, CO 2 produces freezing and avoidance behavior that has been suggested to depend on the amygdala. However, a recent study in humans with bilateral amygdala lesions revealed that CO 2 can trigger fear and panic even in the absence of amygdalae, suggesting the importance of extraamygdalar brain structures. Because the bed nucleus of the stria terminalis (BNST) contributes to fear-and anxiety-related behaviors and expresses acid-sensing ion channel-1A (ASIC1A), we hypothesized that the BNST plays an important role in CO 2 -evoked fear-related behaviors in mice. We found that BNST lesions decreased both CO 2 -evoked freezing and CO 2 -conditioned place avoidance. In addition, we found that CO 2 inhalation caused BNST acidosis and that acidosis was sufficient to depolarize BNST neurons and induce freezing behavior; both responses depended on ASIC1A. Finally, disrupting Asic1a specifically in the BNST reduced CO 2 -evoked freezing, whereas virus-vector-mediated expression of ASIC1A in the BNST of Asic1a Ϫ/Ϫ and Asic1a ϩ/ϩ mice increased CO 2 -evoked freezing. Together, these findings identify the BNST as an extra-amygdalar fear circuit structure important in CO 2 -evoked fear-related behavior.
A divergent synthesis of thioether-functionalized trifluoromethyl-alkynes, 1,3-dienes and allenes viaregioselective nucleophilic addition of sulfur nucleophiles to 2-trifluoromethyl-1,3-conjugated enynes was developed.
With the aging of population, vascular dementia (VaD) seriously threatens people’s health and quality of life. It is of great significance to explore biomarkers of VaD from the perspective of metabolomics and traditional Chinese medicine (TCM). Therefore, VaD was divided into kidney deficiency and blood stasis syndrome (KDBS) and non-KDBS according to TCM. Then, some patients received the treatment of Hengqing I (HQI) prescription. The urine of six groups (VaD group, normal group, KDBS group, non-KDBS group, HQI group, and control group) was detected on LC-MS/MS. Multivariate statistical analysis showed that the metabolic profiles of the three comparisons were significantly different. The top analysis-ready molecules of downregulated histamine and upregulated biotin, methionine, pantothenic acid, SAH, histidine, and kaempferol may be the most related metabolites. These putative biomarkers play an important role in the regulation of key metabolic processes linked to VaD. Additionally, pathway analysis showed aminoacyl-tRNA biosynthesis, and amino acids metabolic pathways were highly correlated with the occurrence of VaD. In this present paper, vitamins, amino acids, and their derivatives were selected as the basis for VaD diagnosis and treatment monitoring, and the significance of TCM classification and Hengqing I prescription in the treatment of VaD was discussed.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.