Fasting produces antidepressant-like effects via activating mammalian target of rapamycin complex 1 signaling pathway in ovariectomized mice.

Recent studies have shown that a 9-hour fast in mice reduces the amount of time spent immobile in the forced swimming test. However, whether 9-hour fasting has therapeutic effects in female mice with depressive symptoms has not been established. Therefore, in this study, we simulated perimenopausal depression via an ovariectomy in mice, and subjected them to a single 9-hour fasting 7 days later. We found that the ovariectomy increased the time spent immobile in the forced swimming test, inhibited expression of the mammalian target of rapamycin complex 1 signaling pathway in the hippocampus and prefrontal cortex, and decreased the density of dendritic spines in the hippocampus. The 9-hour acute fasting alleviated the above-mentioned phenomena. Furthermore, all of the antidepressant-like effects of 9-hour fasting were reversed by an inhibitor of the mammalian target of rapamycin complex 1. Electrophysiology data showed a remarkable increase in long-term potentiation in the hippocampal CA1 of the ovariectomized mice subjected to fasting compared with the findings in the ovariectomized mice not subjected to fasting. These findings show that the antidepressant-like effects of 9-hour fasting may be related to the activation of the mammalian target of the rapamycin complex 1 signaling pathway and synaptic plasticity in the mammalian hippocampus. Thus, fasting may be a potential treatment for depression.

Current Evidence and Future Directions of Berberine Intervention in Depression.

A major type of serious mood disorder, depression is currently a widespread and easily overlooked psychological illness. With the low side effects of natural products in the treatment of diseases becoming the pursuit of new antidepressants, natural Chinese medicine products have been paid more and more attention for their unique efficacy in improving depression. In a view from the current study, the positive antidepressant effects of berberine are encouraging. There is a lot of work that needs to be done to accurately elucidate the efficacy and mechanism of berberine in depression. In this review, the relevant literature reports on the treatment of depression and anxiety by berberine are updated, and the potential pharmacological mechanism of berberine in relieving depression has also been discussed.

Role of CPEB3 protein in learning and memory: new insights from synaptic plasticity.

The cytoplasmic polyadenylation element-binding (CPEB) protein family have demonstrated a crucial role for establishing synaptic plasticity and memory in model organisms. In this review, we outline evidence for CPEB3 as a crucial regulator of learning and memory, citing evidence from behavioral, electrophysiological and morphological studies. Subsequently, the regulatory role of CPEB3 is addressed in the context of the plasticity-related proteins, including AMPA and NMDA receptor subunits, actin, and the synaptic scaffolding protein PSD95. Finally, we delve into some of the more well-studied molecular mechanisms that guide the functionality of this dynamic regulator both during synaptic stimulation and in its basal state, including a variety of upstream regulators, post-translational modifications, and important structural domains that confer the unique properties of CPEB3. Collectively, this review offers a comprehensive view of the regulatory layers that allow a pathway for CPEB3's maintenance of translational control that guides the necessary protein changes required for the establishment and maintenance of lasting synaptic plasticity and ultimately, long term learning and memory.

Role of 5-HT receptors in neuropathic pain: potential therapeutic implications.

5-HT plays a crucial role in the progress and adjustment of pain both centrally and peripherally. The therapeutic action of the 5-HT receptors` agonist and antagonist in neuropathic pain have been widely reported in many studies. However, the specific roles of 5-HT subtype receptors have not been reviewed comprehensively. Therefore, we summarized the recent findings on multiple subtypes of 5-HT receptors in both central and peripheral nervous system in neuropathic pain, particularly, 5-HT1, 5-HT2, 5-HT3 and 5-HT7 receptors. In addition, 5-HT4, 5-HT5 and 5-HT6 receptors were also reviewed. Most of studies focused on the function of 5-HT subtype receptors in spinal level compared to brain areas. Based on these evidences, the pain process can be facilitated or inhibited that depending on the specific subtypes and the distribution of 5-HT receptors. Therefore, this review may provide potential therapeutic implications in treatment of neuropathic pain.

Potential role of insulin on the pathogenesis of depression.

The regulation of insulin on depression and depression-like behaviour has been widely reported. Insulin and activation of its receptor can promote learning and memory, affect the hypothalamic-pituitary-adrenal axis (HPA) balance, regulate the secretion of neurotrophic factors and neurotransmitters, interact with gastrointestinal microbiome, exert neuroprotective effects and have an impact on depression. However, the role of insulin on depression remains largely unclear. Therefore, in this review, we summarized the potential role of insulin on depression. It may provide new insight for clarifying role of insulin on the pathogenesis of depression.

Rapid anti-depressant-like effects of ketamine and other candidates: Molecular and cellular mechanisms.

Major depressive disorder takes at least 3 weeks for clinical anti-depressants, such as serotonin selective reuptake inhibitors, to take effect, and only one-third of patients remit. Ketamine, a kind of anaesthetic, can alleviate symptoms of major depressive disorder patients in a short time and is reported to be effective to treatment-resistant depression patients. The rapid and strong anti-depressant-like effects of ketamine cause wide concern. In addition to ketamine, caloric restriction and sleep deprivation also elicit similar rapid anti-depressant-like effects. However, mechanisms about the rapid anti-depressant-like effects remain unclear. Elucidating the mechanisms of rapid anti-depressant effects is the key to finding new therapeutic targets and developing therapeutic patterns. Therefore, in this review we summarize potential molecular and cellular mechanisms of rapid anti-depressant-like effects based on the pre-clinical and clinical evidence, trying to provide new insight into future therapy.

Role of leptin in the regulation of food intake in fasted mice.

Leptin is well acknowledged as an anorexigenic hormone that plays an important role in feeding control. Hypothalamic GABA system plays a significant role in leptin regulation on feeding and metabolism control. However, the pharmacological relationship of leptin and GABA receptor is still obscure. Therefore, we investigated the effect of leptin or combined with baclofen on the food intake in fasted mice. We detected the changes in hypothalamic c-Fos expression, hypothalamic TH, POMC and GAD67 expression, plasma insulin, POMC and GABA levels to demonstrate the mechanisms. We found that leptin inhibit fasting-induced increased food intake and activated hypothalamic neurons. The inhibitory effect on food intake induced by leptin in fasted mice can be reversed by pretreatment with baclofen. Baclofen reversed leptin's inhibition on c-Fos expression of PAMM in fasted mice. Therefore, these results indicate that leptin might inhibit fasting-triggered activation of PVN neurons via presynaptic GABA synaptic functions which might be partially blocked by pharmacological activating GABA-B. Our findings identify the role of leptin in the regulation of food intake.

Modulation of Multiple Signaling Pathways of the Plant-Derived Natural Products in Cancer.

Natural compounds are highly effective anticancer chemotherapeutic agents, and the targets of plant-derived anticancer agents have been widely reported. In this review, we focus on the main signaling pathways of apoptosis, proliferation, invasion, and metastasis that are regulated by polyphenols, alkaloids, saponins, and polysaccharides. Alkaloids primarily affect apoptosis-related pathways, while polysaccharides primarily target pathways related to proliferation, invasion, and metastasis. Other compounds, such as flavonoids and saponins, affect all of these aspects. The association between compound structures and signaling pathways may play a critical role in drug discovery.

Effect of caloric restriction on depression.

Recently, most of evidence shows that caloric restriction could induce antidepressant-like effects in animal model of depression. Based on studies of the brain-gut axis, some signal pathways were common between the control of caloric restriction and depression. However, the specific mechanism of the antidepressant-like effects induced by caloric restriction remains unclear. Therefore, in this article, we summarized clinical and experimental studies of caloric restriction on depression. This review may provide a new therapeutic strategy for depression.

Ghrelin produces antidepressant-like effect in the estrogen deficient mice.

Recent evidence shows that ghrelin plays an important role in depression. However, it was little known whether ghrelin produces antidepressant-like effect in the ovariectomized mice. The present study was aimed to investigate the antidepressant-like effects of the ghrelin in ovariectomized mice. In the forced swim test, ghrelin significantly decreased immobility time, reversing the "depressive-like" effect observed in ovariectomized mice, and this effect was reversed by the tamoxifen. In addition, immunohistochemical study indicated that ghrelin treatment reversed the reductions in c-Fos expression induced by ovariectomy. An estrogen antagonist tamoxifen also antagonized the effect of ghrelin on the c-Fos expression. Furthermore, the western blotting indicated that brain-derived neurotrophic factor (BDNF) in the hippocampus, but not phosphorylated cAMP response element-binding protein (pCREB)/CREB in the frontal cortex, were affected by ghrelin treatment. Ghrelin treatment significantly increased BrdU expression. Therefore, these findings suggest that ghrelin produces antidepressant-like effects in ovariectomized mice, and estrogen receptor may be involved in the antidepressant-like effects of the ghrelin.

Affective Processing in Non-invasive Brain Stimulation Over Prefrontal Cortex.

The prefrontal cortex (PFC) is the most frequently targeted brain region by non-invasive brain stimulation (NBS) studies. Non-invasively stimulating the PFC has been shown to both modulate affective processing and improve the clinical symptoms of several psychiatric disorders, such as depression and schizophrenia. The magnitude of the modulation depends on several factors, including the stimulation frequency, the number of stimulation sessions, and the specific sub-region of the PFC that is stimulated. Although some of the potential underlying mechanisms have been identified, the exact mechanisms that underlie these cognitive and affective changes remain unclear. The present review aims to summarize recent advances in the study of affective processing using NBS over the PFC. We will provide a theoretical framework for better understanding how affective processing changes are induced by NBS, with the goal of providing testable hypotheses for future studies.