Fluoxetine mitigates depressive-like behaviors in mice via anti-inflammation and enhancing neuroplasticity.

Neuroplasticity and inflammation represent a common final pathway for effective antidepressant treatment. SSRIs are the most commonly prescribed medications for depression and have demonstrated efficacy in reducing depressive symptoms. However, the precise impact of SSRIs on neuroplasticity and inflammation remains unclear. In this study, we aimed to investigate the influence of long-term treatment with SSRIs on hippocampal neuron, inflammation, synaptic function and morphology. Our findings revealed that fluoxetine treatment significantly alleviated behavioral despair, anhedonia, and anxiety in reserpine-treated mice. Moreover, fluoxetine mitigated hippocampal neuron impairment, inhibited inflammatory release, and increased the expression of synaptic proteins markers (SYP and PSD95) in mice. Notably, fluoxetine also suppressed reserpine-induced synapse loss in the hippocampus. Based on these results, fluoxetine has been demonstrated effectively to ameliorate depressive mood and cognitive dysfunction, possibly through the enhancement of synaptic plasticity. Overall, our study contributes to a further understanding of the mechanisms underlying the therapeutic effects of fluoxetine and its potential role in improving depressive symptoms and cognitive impairments.

Monozygotic Twins Suffering From Sodium Taurocholate Cotransporting Polypeptide Deficiency: A Case Report.

Sodium taurocholate cotransporting polypeptide (NTCP) is a carrier protein encoded by the human SLC10A1 gene, acting as the principal transporter of conjugated bile salts from the plasma into hepatocytes. Although NTCP was cloned as early as in 1994 and its function has been studied extensively, clinical description of NTCP deficiency remains rather limited thus far. The patients in this paper were 2 female monozygotic twins, who were referred to our hospital at the age 2 years with the complaint of persistently-raised total bile acids (TBA) for 21 months. At age 3 months, they were both diagnosed to have cholestatic liver disease due to raised serum TBA and direct bilirubin (DBIL) with the fraction >20% of the elevated total bilirubin (TBIL). Thereafter, their jaundice subsided and the DBIL levels recovered gradually, while serum TBA remained raised persistently. In view of their refractory hypercholanemia but negative symptoms and signs, SLC10A1 genetic analysis was performed for all family members to evaluate the possibility of NTCP deficiency. As a result, the twins were both homozygotes, while the parents, carriers, of the reportedly pathogenic variant c.800C>T (p.Ser267Phe). These findings suggested that NTCP deficiency may be a unique genetic factor causing transient cholestasis in early infancy, as well as, persistent hypercholanemia in pediatric patients.

SCN1A, SCN2A and SCN3A gene polymorphisms and responsiveness to antiepileptic drugs: a multicenter cohort study and meta-analysis.

AIM: Approximately a third of newly diagnosed epilepsy patients do not respond to antiepileptic drugs (AEDs). Evidence suggests that low penetrance variants in the genes of drug targets such as voltage-gated sodium channels may be involved in drug responsiveness. To examine this hypothesis, we compared data from two epilepsy cohorts from Malaysia and Hong Kong, as well as a meta-analysis from published data. MATERIALS & METHODS: Genotype analysis of 39 polymorphisms located in the SCN1A, SCN2A and SCN3A genes was performed on 1504 epilepsy patients from Malaysia and Hong Kong who were receiving AEDs. Meta-analysis was performed for pooled data of SCN1A rs3812718 and rs2298771, and SCN2A rs17183814 polymorphisms. RESULTS: Our data from the Hong Kong and Malaysia cohorts showed no significant allele, genotype and haplotype association of polymorphisms in the SCN1A, SCN2A, and SCN3A genes with drug responsiveness in epilepsy. This finding was supported by a meta-analysis for SCN1A rs3812718 and rs2298771, and for SCN2A rs17183814 polymorphisms. CONCLUSION: Our comprehensive study suggests that common polymorphisms in SCN1A, SCN2A and SCN3A do not play major roles in influencing response to AEDs. Original submitted 11 March 2013; Revision submitted 31 May 2013.