Repurposing antimalarial artesunate for the prophylactic treatment of depression: Evidence from preclinical research.

INTRODUCTION: Several studies have linked inflammation and oxidative stress with the pathogenesis of depression. Artesunate is a commonly used medication to treat malaria and has been shown to produce antioxidant, anti-inflammatory, and immunomodulatory effects. However, its prophylactic effects on depression and depression-related brain pathology are unknown. METHODS: In Experiment 1, using a PC12 cell line, we investigated whether artesunate can prevent hydrogen peroxide (H2 O2 )-induced oxidative injury that mimics oxidative stress commonly observed in the depressed brain. Next, using lipopolysaccharide (LPS)-induced mouse model of depression, we investigated whether artesunate can prevent behavioral deficits observed in the open field test, novelty-suppressed feeding test, sucrose preference test, forced swimming test, and tail suspension procedure. RESULTS: We found that artesunate significantly prevented a H2 O2 -induced reduction in PC12 cell activity, suggesting its antioxidant potential. We also found that mice pretreated with artesunate (5, 15 mg/kg) intraperitoneally (i.p.) prior to the LPS (.8 mg/kg, i.p.) treatment showed fewer and less severe depression- and anxiety-like behaviors than the LPS-treated control mice. CONCLUSION: Our findings indicate that artesunate produces antioxidant effect, as well as antidepressant and anxiolytic effects. Importantly, our findings first demonstrate that artesunate can prevent LPS-induced depression- and anxiety-like symptoms, strongly suggesting its prophylactic potential in the treatment of depression and, perhaps, other psychiatric disorders associated with inflammation and oxidative stress.

The novel HLA-C*03:605 allele, identified using next-generation sequencing in a Chinese individual.

The HLA-C*03:605 allele differs from HLA-C*03:04:01:01 by a single nucleotide in exon 4, position 680.

The novel allele HLA-B*35:564, identified by next-generation sequencing in a Chinese individual.

The novel HLA-B*35:564 allele differs from the HLA-B*35:01:01:01 allele by one nucleotide in exon 3 at position 490.

A novel HLA-C allele, HLA-C*03:614, identified by next-generation sequencing in a Chinese individual.

HLA-C*03:614 has one nucleotide change compared with HLA-C*03:02:02:01 in exon 7, codon 336.

Long-lasting and Sex-dependent Effects of Postweaning Swimming Exercise on Social Dominance in Adult Mice.

Increasing evidence has shown that early life events exert long-lasting effects on brain function and mental diseases. Exercise has been proven to have many positive effects on behaviors, such as reducing anxiety- and depression-like behaviors and alleviating cognitive impairment. However, the long-lasting and even short-term effects of regular swimming exercise on social dominance remain unclear. The purpose of this study was to investigate the potential effects of postweaning swimming exercise on social dominance and metabolic adaptation in adult mice. Three-week-old mice performed 1 h of swimming exercise in warm water for 4 weeks. A series of behavioral tests, such as the social dominance test (SDT), open field test (OFT), and forced swim test (FST), were conducted. Behavioral test results showed that both male and female mice in the swimming group had a higher rank than those in the sedentary group in the SDT of early adulthood, while only female mice in the swimming group maintained the social dominance in late adulthood. There was no difference between the swimming and sedentary groups in anxiety- and depression-like behaviors. Metabolomics analysis showed that there were alterations in particular metabolites and signaling pathways after one month of swimming exercise, including sphingolipid metabolism, neuroactive ligand-receptor interaction and caffeine metabolism. In conclusion, our results provide the first evidence that postweaning swimming exercise has long-lasting and sex-dependent effects on social dominance, which may be caused by metabolic adaptation.

Identification of two novel HLA class II alleles, HLA-DQB1*02:139 and HLA-DQB1*02:140, in northern Chinese individuals.

Two novel HLA-DQB1 alleles, HLA-DQB1*02:139 and HLA-DQB1*02:140, characterized using a sequence-based typing in northern Chinese individuals.