ABSTRACT
Nowadays, infertility related diseases become one of the basic challenges in societies. Human fertilization and fetal development are one of the most complex biological process, influenced by various factors, such as exosomes. Exosomes are Nano-sized bilayer-lipid membrane vesicles that play a role in mediating cell to cell communication in the reproductive system by serving as carriers of different biomolecules. Alterations in exosomes number and contents also can be seen in different male and female reproductive diseases in animals and human cases. These nanoparticles have great potential to become a large-scale therapeutic platform in the field of regenerative medicine. Diagnostic and therapeutic properties of exosomes have opened new windows of hope for using these compounds in the diagnosis and treatment of many diseases, especially pregnancy disorders. Various methods including direct injection, intravenous injection, intraperitoneal injection, oral administration, and hydrogel-based encapsulation for targeted delivery of exosomes have been investigated in different disease models. The most recent advances in the development of exosome-functionalized biomaterials that mediate enhanced preservation exosome bioactivity and controlled release, have been presented. This review highlights the potential medical applications of exosomes with emphasis on diagnostic and therapeutic effects of exosomes on male and female reproductive system related diseases. In addition, the advantages of the biomaterial-based exosome delivery systems have been examined in this review.
Subject(s)
Exosomes , Infertility, Female , Nanoparticles , Animals , Humans , Female , MaleABSTRACT
The effect of maternal forced exercise on central disorders in offsprings has been shown but the mechanism is still unclear. In this study, the role of 5-HT2 and D2 receptors in neuroprotective effects of maternal forced exercise on offspring neurodevelopment and neurobehavioral symptoms is evaluated. Sixty pregnant rats were trained by forced exercise and some behavioral and molecular aspects in their offspring were evaluated in presence of 5-HT2 and D2 receptors agonists and antagonists. The results showed that maternal forced exercise causes increase of pain tolerability and increase latency of pain perception in offspring in hot plate test, writhing test and tail flick test. Also maternal forced exercise causes decrease of depression and anxiety like behavior in offsprings. On the other hand, treatment of mothers by forced exercise in combination with 5-HT2 and D2 receptor antagonists inhibited the protective effects of forced exercise and cause disturbance in pain perception and tolerability and increase depression and anxiety in offsprings. Also expression of cyclic AMP response element binding protein (CREB) was changed in all experimental groups. In conclusion, our data suggested that maternal forced exercise causes neurobehavioral protective effect on offsprings and this effect might probably be mediated by 5-HT2 and D2 receptors and activation of CREB gene expression.
ABSTRACT
Chronic abuse of methylphenidate (MPH) often causes neuronal cell death. Topiramate (TPM) carries neuroprotective effects, but its exact mechanism of action remains unclear. In the present study, the role of various doses of TPM and its possible mechanisms, receptors and signaling pathways involved against MPH-induced hippocampal neurodegeneration were evaluated in vivo. Thus, domoic acid (DOM) was used as AMPA/kainate receptor agonist, bicuculline (BIC) as GABAA receptor antagonist, ketamine (KET) as NMDA receptor antagonist, yohimbine (YOH) as α2 adrenergic receptor antagonist and haloperidol (HAL) was used as dopamine D2 receptor antagonist. Open field test (OFT) was used to investigate the disturbances in motor activity. Hippocampal neurodegenerative parameters were evaluated. Protein expressions of CREB/BDNF and Akt/GSK3 signaling pathways were also evaluated. Cresyl violet staining was performed to show and confirm the changes in the shape of the cells. TPM (70 and 100 mg/kg) reduced MPH-induced rise in lipid peroxidation, oxidized form of glutathione (GSSG), IL-1ß and TNF-α levels, Bax expression and motor activity disturbances. In addition, TPM treatment increased Bcl-2 expression, the level of reduced form of glutathione (GSH) and the levels and activities of superoxide dismutase, glutathione peroxidase and glutathione reductase enzymes. TPM also inhibited MPH-induced hippocampal degeneration. Pretreatment of animals with DOM, BIC, KET and YOH inhibited TPM-induced neuroprotection and increased oxidative stress, neuroinflammation, neuroapoptosis and neurodegeneration while reducing CREB, BDNF and Akt protein expressions. Also pretreatment with DOM, BIC, KET and YOH inhibited TPM-induced decreases in GSK3. It can be concluded that the mentioned receptors by modulation of CREB/BDNF and Akt/GSK3 pathways, are involved in neuroprotection of TPM against MPH-induced neurodegeneration.