Lactobacillus paragasseri OLL2809 Improves Depression-Like Behavior and Increases Beneficial Gut Microbes in Mice.

Lactobacillus paragasseri OLL2809 is a probiotic bacterial strain isolated from healthy human feces. While OLL2809 has been studied for its immunomodulatory activities, its effect on depressive-like behaviors remains unclear. In this study, we used a mouse model of social defeat stress (SDS) to investigate whether oral administration of OLL2809 ameliorates depressive-like behavior. C57BL6 male mice were administered OLL2809 for 2 weeks following a 4-week period of SDS. Although OLL2809 did not affect serum corticosterone levels, it ameliorated depression-like behaviors, and it induced neurite outgrowth in the hippocampal dentate gyrus. The 16S rRNA amplicon sequence analyses revealed that family level gut microbiota composition was affected by stress and OLL2809 administration. Additionally, Akkermansia muciniphila, Bifidobacterium, and Lactobacillus were significantly increased by OLL2809 treatment. LEfSe analysis suggested that the antidepressive effect of OLL2809 may be mediated by increases in other microorganisms, such as Erysipelotrichaceae uncultured. Our findings suggest that L. paragasseri OLL2809 may have potential in microbiome therapeutics.

CGRP overexpression does not alter depression-like behavior in mice.

BACKGROUND: The calcitonin gene-related peptide (CGRP) is a neuropeptide that is released from capsaicin-sensitive nerves as a potent vasodilator involved in nociceptive transmission. While CGRP has been rigorously studied for its role in migraines owing to its vasodilation and inflammation activities, the effects of CGRP overexpression on depressive-like behaviors remain insufficiently understood. METHODS: In the present study, we performed a battery of behavioral tests, including the social interaction test, open field test, and sucrose preference test, to evaluate social defeat stress using male C57BL6J or CGRP overexpression in transgenic (Tg) mice (CGRP Tg). We performed mRNA and protein analyses on the brain-derived neurotrophic factor (BDNF), phosphorylated Akt, mTOR, and p70S6K in the hippocampi. RESULTS: CGRP Tg mice showed increased levels of Bdnf mRNAs, low locomotor activity, and no deficits in social interaction, which indicate that CGRP Tg mice exhibit stress resistance and not depression. However, the open field test significantly decreased after 15-day social defeat stress exposure. We also evaluated depressive-like behavior using the sucrose preference and social interaction tests. Our data indicate that defeated CGRP Tg mice exhibited a depressive-like phenotype, which was inferred from increased social avoidance and reduced sucrose preference compared with non-defeated controls. Although stress exposure did not change the BDNF levels in CGRP Tg mice, it significantly decreased the expression levels of p-Akt, p-mTOR and p-p70S6K in the mice hippocampi. We conclude that CGRP-overexpressing Tg mice have normal sensitivity to stress and down-regulated hippocampal Akt/mTOR/p70S6K pathways.

Roman chamomile inhalation combined with clomipramine treatment improves treatment-resistant depression-like behavior in mice.

It is well known that chamomile is one of the oldest known medicinal herbs and has been used to treat various disorders, but it is mainly German chamomile. The effects of Roman chamomile on depression still unclear. In this study, we used chronically stressed mice to investigate whether inhalation of Roman chamomile essential oil affects depression-like behavior. We previously reported that restraint and water immersion stress produce depression-like behavior and a blunted response to the tricyclic antidepressant clomipramine. Each mouse was exposed to restraint and water immersion stress for 15 days, and resistance to the effect of clomipramine was induced in a behavioral despair paradigm. In the present study, we found that cotreatment with clomipramine and inhalation of Roman chamomile attenuated depression-like behavior in a forced swim test. Next, we examined the hippocampal mRNA levels of two cytokines, tumor necrosis factor (TNF) alpha and interleukin-6 (IL-6); a neurotrophic factor, brain derived-neurotrophic factor (BDNF); and nerve growth factor (NGF). TNF alpha, IL-6 and BDNF mRNA levels did not change in the hippocampus of stressed mice. However, the NGF mRNA level was significantly decreased, and this decrease was not attenuated by treatment with clomipramine or inhalation of Roman chamomile alone. We also examined whether Roman chamomile combined with clomipramine treatment affects hippocampal neurogenesis and serum corticosterone levels. Stressed mice had fewer doublecortin (DCX)-positive cells in the subgranular zone of the dentate gyrus, but this was significantly attenuated by Roman chamomile and clomipramine treatment. In addition, the serum corticosterone level was also significantly decreased by treatment with Roman chamomile and clomipramine. These results suggest that Roman chamomile inhalation may enhance the antidepressant effect of clomipramine by increasing hippocampal neurogenesis and modulating corticosterone levels in patients with treatment-resistant depression.

[αCGRP Transgenic Mice Display Typical Physiologic Features].

Calcitonin gene-related peptide (CGRP) plays an important role in several physiological processes such as vasodilation, cardiovascular homeostasis and transmission of pain. Here we report the generation of a transgenic mouse overexpressing αCGRP and the impact of this on baseline physiological responses. αCGRP transgenic mice displayed significantly increased αCGRP mRNA levels in the kidney, heart and hippocampus. To assess cardiovascular physiology, we measured arterial pressure using a tail cuff system. Heart rate, systolic pressure, mean arterial pressure and diastolic pressure were significantly lower in αCGRP transgenic mice than wild-type mice. To assess pain, a hot plate test was performed and the latency of response was used as an indicator of supraspinal response. In addition, a tail immersion test was performed to assess thermal nociception. A significant increase in latency was observed in the αCGRP transgenic mice when compared with wild-type mice in both tests. These results suggest that αCGRP overexpression causes an increase in thermal reaction and downregulation of the cardiovascular system, presumably due in increased levels of αCGRP.

Effects of alcoholic beverage treatment on spatial learning and fear memory in mice.

Although chronic ethanol treatment is known to impair learning and memory, humans commonly consume a range of alcoholic beverages. However, the specific effects of some alcoholic beverages on behavioral performance are largely unknown. The present study compared the effects of a range of alcoholic beverages (plain ethanol solution, red wine, sake and whiskey; with a matched alcohol concentration of 10%) on learning and memory. 6-week-old C57BL6J mice were orally administered alcohol for 7 weeks. The results revealed that red wine treatment exhibited a trend toward improvement of spatial memory and advanced extinction of fear memory. Additionally, red wine treatment significantly increased mRNA levels of brain-derived neurotrophic factor (BDNF) and N-methyl-D-aspartate (NMDA) receptors in mice hippocampus. These results support previous reports that red wine has beneficial effects.