Depression is one of the major mental disorders, which seriously endangers human health, brings a serious burden to patients’ families. In this study, we intended to further explore the antidepressant-like effect and possible molecular mechanisms of Salidroside (SAL). We built corticosterone (CORT)-induced depressive mice model and used behavioural tests to evaluate depression behaviour. To explore the molecular mechanisms of SAL, we employed a variety of methods such as immunofluorescence, western blot, pharmacological interference, etc. The results demonstrated that SAL both at 25 mg/kg and 50 mg/kg can reduce immobility time in the tail suspension test (TST). At the same time, SAL treatment could restore the reduced sugar water intake preference in the sucrose preference test (SPT) in CORT-induced depressive mice and reduce the immobility time in TST and forced swimming experiments (FST). In addition, SAL treatment reversed the reduction in the number of Ki-67, BrdU, and NeuN in the hippocampus due to CORT treatment. SAL treatment also restored the expression of SIRT1, PGC-1α, brain-derived neurotrophic factor (BDNF) and other proteins in the hippocampus. In addition, after blocking SIRT1 signalling with EX527, we found that the treatment with SAL failed to reduce the immobility time in TST and FST, the level of SIRT1 and PGC-1α activity were correspondingly downregulated, and the expression of DCX and Ki-67 in the hippocampus failed to be activated. These findings suggested that SAL exerts antidepressant-like effects by promoting hippocampal neurogenesis through the SIRT1/PGC-1α signalling pathway.

Brain ageing, the primary risk factor for cognitive impairment, occurs because of the accumulation of age-related neuropathologies. Identifying effective nutrients that increase cognitive function may help maintain brain health. Tomatoes and lemons have various bioactive functions and exert protective effects against oxidative stress, ageing and cancer. Moreover, they have been shown to enhance cognitive function. In the present study, we aimed to investigate the effects of tomato and lemon ethanolic extracts (TEE and LEE, respectively) and their possible synergistic effects on the enhancement of cognitive function and neurogenesis in aged mice. The molecular mechanisms underlying the synergistic effect of TEE and LEE were investigated. For the in vivo experiment, TEE, LEE or their mixture was orally administered to 12-month-old mice for 9 weeks. A single administration of either TEE or LEE improved cognitive function and neurogenesis in aged mice to some extent, as determined using the novel object recognition test and doublecortin immunohistochemical staining, respectively. However, a significant enhancement of cognitive function and neurogenesis in aged mice was observed after the administration of the TEE + LEE mixture, which had a synergistic effect. N-methyl-d-aspartate receptor 2B, postsynaptic density protein 95, and brain-derived neurotrophic factor (BDNF) levels and tropomyosin receptor kinase B (TrkB)/extracellular signal-regulated kinase (ERK) phosphorylation also synergistically increased after the administration of the mixture compared with those in the individual treatments. In conclusion, compared with their separate treatments, treatment with the TEE + LEE mixture synergistically improved the cognitive function, neurogenesis and synaptic plasticity in aged mice via the BDNF/TrkB/ERK signalling pathway.

Endometriosis is a chronic inflammatory disease with pelvic pain and uncharacteristic accompanying symptoms. Endometriosis-associated pain often persists despite treatment of the disease, thus it brings a deleterious impact on their personal lives as well as imposing a substantial economic burden on them. At present, mechanisms underlie endometriosis-associated pain including inflammatory reaction, injury, aberrant blood vessels and the morphological and functional anomaly of the peripheral and central nervous systems. The nerve endings are influenced by the physical and chemical factors surrounding the lesion, via afferent nerve to the posterior root of the spinal nerve, then to the specific cerebral cortex involved in nociception. However, our understanding of the aetiology and mechanism of this complex pain process caused by endometriosis remains incomplete. Identifying the pathogenesis of endometriosis is crucial to disease management, offering proper treatment, and helping patients to seek novel targets for the maintenance and contributors of chronic pain. The main aim of this review is to focus on every possible mechanism of pain related to endometriosis in both peripheral and central nervous systems, and to present related mechanisms of action from the interaction between peripheral lesions and nerves to the changes in transmission of pain, resulting in hyperalgesia and the corresponding alterations in cerebral cortex and brain metabolism.

Calorie restriction (CR) has been shown to be one of the most effective methods in alleviating the effects of ageing and age-related diseases. Although the protective effects of CR have been reported, the exact molecular mechanism still needs to be clarified. This study aims to determine differentially expressed (DE) miRNAs and altered gene pathways due to long-term chronic (CCR) and intermittent (ICR) CR in the brain of mice to understand the preventive roles of miRNAs resulting from long-term CR. Ten weeks old mice were enrolled into three different dietary groups; ad libitum, CCR or ICR, and fed until 82 weeks of age. miRNAs were analysed using GeneChip 4.1 microarray and the target of DE miRNAs was determined using miRNA target databases. Out of a total 3,163 analysed miRNAs, 55 of them were differentially expressed either by different CR protocols or by ageing. Brain samples from the CCR group had increased expression levels of mmu-miR-713 while decreasing expression levels of mmu-miR-184-3p and mmu-miR-351-5p compared to the other dietary groups. Also, current results indicated that CCR showed better preventive effects than that of ICR. Thus, CCR may perform its protective effects by modulating these specific miRNAs since they are shown to play roles in neurogenesis, chromatin and histone regulation. In conclusion, these three miRNAs could be potential targets for neurodegenerative and ageing-related diseases and may play important roles in the protective effects of CR in the brain.

Neuronal plasticity or remodeling is most often discussed with regard to cellular and behavioral models of learning and memory. However, neuronal plasticity is a fundamental process by which the brain acquires information and makes the appropriate adaptive responses in future-related settings. Dysfunction of these fundamental processes could thereby contribute to the pathophysiology of mood disorders, and recovery could occur by induction of the appropriate plasticity or remodeling. These possibilities are supported by preclinical and clinical studies demonstrating that there are structural alterations that occur in response to stress and in patients with mood disorders. Moreover, antidepressant treatment may oppose these effects by regulation of signal transduction and gene expression pathways linked to neuronal plasticity. These findings comprise a novel conceptual framework for future studies of the etiology of mood disorders and for the development of novel therapeutic interventions.

The aim of this review is to summarize the present state of findings on altered neurotrophic factor levels in schizophrenic psychoses, on variations in genes coding for neurotrophic factors, and on the effect of antipsychotic drugs on the expression level of neurotrophic factors. This is a conceptual paper that aims to establish the link between the neuromaldevelopment theory of schizophrenia and neurotrophic factors. An extensive literature review has been done using the Pub Med database, a service of the National Library of Medicine, which includes over 14 million citations for biomedical articles back to the 1950s. The majority of studies discussed in this review support the notion of alterations of neurotrophic factors at the protein and gene level, respectively, and support the hypothesis that these alterations could, at least partially, explain some of the morphological, cytoarchitectural and neurobiochemical abnormalities found in the brain of schizophrenic patients. However, the results are not always conclusive and the clinical significance of these alterations is not fully understood. It is, thus, important to further neurotrophic factor research in order to better understand the etiopathogenesis of schizophrenic psychoses and, thus, potentially develop new treatment strategies urgently needed for patients suffering from these devastating disorders.

Ageing is characterised by memory deficits, associated with brain plasticity impairment. Polyphenols from berries, such as flavan-3-ols, anthocyanins, and resveratrol, have been suggested to modulate synaptic plasticity and cognitive processes. In the present study we assessed the preventive effect of a polyphenol-rich extract from grape and blueberry (PEGB), with high concentrations of flavonoids, on age-related cognitive decline in mice. Adult and aged (6 weeks and 16 months) mice were fed a PEGB-enriched diet for 14 weeks. Learning and memory were assessed using the novel object recognition and Morris water maze tasks. Brain polyphenol content was evaluated with ultra-high-performance LC-MS/MS. Hippocampal neurotrophin expression was measured using quantitative real-time PCR. Finally, the effect of PEGB on adult hippocampal neurogenesis was assessed by immunochemistry, counting the number of cells expressing doublecortin and the proportion of cells with dendritic prolongations. The combination of grape and blueberry polyphenols prevented age-induced learning and memory deficits. Moreover, it increased hippocampal nerve growth factor (Ngf) mRNA expression. Aged supplemented mice displayed a greater proportion of newly generated neurons with prolongations than control age-matched mice. Some of the polyphenols included in the extract were detected in the brain in the native form or as metabolites. Aged supplemented mice also displayed a better survival rate. These data suggest that PEGB may prevent age-induced cognitive decline. Possible mechanisms of action include a modulation of brain plasticity. Post-treatment detection of phenolic compounds in the brain suggests that polyphenols may act directly at the central level, while they can make an impact on mouse survival through a potential systemic effect.

Cannabinoid signalling modulates several aspects of brain function, including the generation and survival of neurons during embryonic and adult periods. The present review intended to summarise evidence supporting a role for the endocannabinoid system on the control of neurogenesis and neurogenesis-dependent functions. Studies reporting participation of cannabinoids on the regulation of any step of neurogenesis and the effects of cannabinoid compounds on animal models possessing neurogenesis-dependent features were selected from Medline. Qualitative evaluation of the selected studies indicated that activation of cannabinoid receptors may change neurogenesis in embryonic or adult nervous systems alongside rescue of phenotypes in animal models of different psychiatric and neurological disorders. The text offers an overview on the effects of cannabinoids on central nervous system development and the possible links with psychiatric and neurological disorders such as anxiety, depression, schizophrenia, brain ischaemia/stroke and Alzheimer’s disease. An understanding of the mechanisms by which cannabinoid signalling influences developmental and adult neurogenesis will help foster the development of new therapeutic strategies for neurodevelopmental, psychiatric and neurological disorders.

According to classical knowledge of reproductive biology, in the ovary of female mammals there is a limited number of oocytes and there is no possibility of renewal if the oocytes are lost due to disease or injury. However, in recent years, the results of some studies on renewal and formation of oocytes and follicles in the adult mammalian ovary have led to the questioning of this opinion. The aim of our study is to demonstrate the presence of putative germline and pluripotent stem cells in the adult mouse ovary and their differentiation potential into germ and somatic cells. In ovary tissues and cells harvested from pre-differentiation step, the expression of pluripotent and germline stem cell markers was analysed by reverse transcription-polymerase chain reaction (RT-PCR), immunofluorescence staining and western blotting. Embryoid bodies that formed in this step were analysed using immunofluorescence staining and transmission electron microscopy. Ovarian stem cells were induced to differentiate into oocyte, osteoblast, chondrocyte and neural cells. Besides morphological observation, differentiated cells were analysed by RT-PCR, histochemical and immunofluorescence staining. Expression of germline and pluripotent stem cell markers both in mRNA and at the protein level were detected in the pre-differentiated cells and ovary tissues. As a result of the differentiation process, the formation of oocyte-like cells, osteoblasts, chondrocytes and neural cells was observed and characteristics of differentiated cells were confirmed using the methods mentioned above. Our study results revealed that the adult mouse ovary contains germline and pluripotent stem cells with the capacity to differentiate into oocyte-like cells, osteoblasts, chondrocytes and neural cells.

Three areas in the brain continuously generate new neurons throughout life: the subventricular zone lining the lateral ventricles, the dentate gyrus in the hippocampus and the median eminence in the hypothalamus. These areas harbour neural stem cells, which contribute to neural repair by generating daughter cells that then become functional neurons or glia. Impaired neurogenesis leads to detrimental consequences, such as depression, decline of cognitive abilities and obesity. Adult neurogenesis is a versatile process that can be modulated either positively or negatively by many effectors, external or endogenous. Diet can modify neurogenesis both ways, either directly by ways of food-borne molecules, or possibly by the modifications induced on gut microbiota composition. It is therefore critical to define dietary strategies optimal for the maintenance of the stem cell pools.

Previously, it has been shown that strawberry (SB) or blueberry (BB) supplementations, when fed to rats from 19 to 21 months of age, reverse age-related decrements in motor and cognitive performance. We have postulated that these effects may be the result of a number of positive benefits of the berry polyphenols, including decreased stress signalling, increased neurogenesis, and increased signals involved in learning and memory. Thus, the present study was carried out to examine these mechanisms in aged animals by administering a control, 2 % SB- or 2 % BB-supplemented diet to aged Fischer 344 rats for 8 weeks to ascertain their effectiveness in reversing age-related deficits in behavioural and neuronal function. The results showed that rats consuming the berry diets exhibited enhanced motor performance and improved cognition, specifically working memory. In addition, the rats supplemented with BB and SB diets showed increased hippocampal neurogenesis and expression of insulin-like growth factor 1, although the improvements in working memory performance could not solely be explained by these increases. The diverse polyphenolics in these berry fruits may have additional mechanisms of action that could account for their relative differences in efficacy.

Substantial evidence exists for a cohort effect (earlier onset and increased prevalence) for both unipolar and bipolar affective disorder in every generation born since World War II. This effect could be related to inherited mechanisms (e.g., bi-Hneal pedigrees or genetic anticipation) or to environmental/experiential effects on gene expression (e.g., stressor effects on the induction of transcription and growth factors, enzymes, hormones and their receptors, and signal transduction molecules) as documented in preclinical models of neonatal maternal separation.

This laboratory evidence is summarized and new clinical data on the impact of severe stressors on the unfolding course of bipolar illness are noted. The reported occurrence of childhood or adolescent physical or sexual abuse, compared to those who report their absence, is associated with: earlier bipolar illness onset; faster cycling (including ultradian) patterns; increased Axis I and II comorbidities; and increased time ill in a prospective year of follow-up. Selectively, physical abuse was associated with a reported pattern of increasingly severe mania and sexual abuse with increased numbers of serious suicide attempts.

In a retrospective survey of parents of children with an approximate average age of 13 who were diagnosed with bipolar illness (compared to those with other diagnoses and those with no diagnosis), a cluster of symptoms related to irritability and dyscontrol differentiated the bipolar children earliest. These symptoms included: temper tantrums, irritability, inattention, hyperactivity, impulsivity, poor frustration tolerance, and increased aggression.

Given the growing evidence that episodes of affective dysfunction can not only convey morbidity and mortality, but may also sensitize to further recurrence and thus change the course of illness, opportunities abound for early recognition and intervention in childhood onset bipolar illness. Such a successful endeavor would both allow a more normal psychobiological development and allow the possibility of preventing the unfolding of more full-blown bipolar illness altogether.