Neuroscience
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High levels of 17β-estradiol (E2) have been found to reduce inflammatory temporomandibular joint (TMJ) pain. A search for genes effected by a high concentration of estradiol showed an increase in GABAA receptor subunit alpha 6 (Gabrα6) in the trigeminal ganglia (TG). Blockade of Gabrα6 expression in the TG increases masseter muscle nociception in male rats, but the relationship between estradiol's effect on nociception and Gabrα6 expression remains unclear in females. ⋯ Ligature significantly increased the nociceptive response but a high proestrus concentration of 17β-estradiol attenuated this response. Gabrα6 siRNA infusion decreased Gabrα6 expression in the TG and Vc-C1 but increased the nociceptive response after 17β-estradiol treatment. The results suggest estradiol decreased the orofacial nociceptive response, in part, by causing an increase in Gabrα6 expression.
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Short- and long-term treatment with modafinil differentially affects adult hippocampal neurogenesis.
The generation of new neurons in the dentate gyrus of the adult brain has been demonstrated in many species including humans and is suggested to have functional relevance for learning and memory. The wake promoting drug modafinil has popularly been categorized as a so-called neuroenhancer due to its positive effects on cognition. We here show that short- and long-term treatment with modafinil differentially effects hippocampal neurogenesis. ⋯ Interestingly, long-term treatment for 14days resulted in an increased number of newborn Prox1(+) granule cells, but we could not detect an additive effect of the prolonged treatment on proliferation and survival of newborn cells. Moreover, daily administration for 14days did not influence the number of proliferating cells in the dentate gyrus. Together, modafinil has an acute impact on precursor cell proliferation as well as survival but loses this ability during longer treatment durations.
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Tetramethylpyrazine (TMP) is an active compound extracted from the traditional Chinese medicinal herb Chuanxiong. Recently, it has been reported that TMP enhances neurogenesis, and promotes neural stem cell differentiation toward neurons. However, its molecular basis remains unknown. ⋯ We further performed chromatin immunoprecipitation (ChIP) analysis and identified that TMP enhanced the recruitment of Ac-H3 and Ac-H4 to the TopoIIβ gene promoter region. Therefore, we concluded that TMP may stimulate neuronal differentiation of SH-SY5Y cells through epigenetic regulation of TopoIIβ. These results suggest a novel molecular mechanism underlying TMP-promoted neuronal differentiation.
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Gliomas are the most common malignant intracranial tumors. Newly developed targeted therapies for these cancers aim to inhibit oncogenic signals, many of which emanate from receptor tyrosine kinases, including the epidermal growth factor receptor (EGFR) and the vascular endothelial growth factor receptor (VEGFR). Unfortunately, the first-generation treatments targeting these oncogenic signals provide little survival benefit in both mouse xenograft models and human patients. ⋯ GPCRs constitute a large family of membrane receptors that influence oncogenic pathways through canonical and non-canonical signaling. Accordingly, evidence indicates that GPCRs display a unique ability to crosstalk with receptor tyrosine kinases, making them important molecular components controlling tumorigenesis. This review summarizes the current research on GPCR functionality in gliomas and explores the potential of modulating these receptors to treat this devastating disease.
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The involvement of the central nervous system in the pathophysiology of temporomandibular disorders (TMD) has been noticed. TMD patients have been shown dysfunction of motor performance and reduced cognitive ability in neuropsychological tests. The aim of this study is to explore the spontaneous neural activity in TMD patients with centric relation (CR)-maximum intercuspation (MI) discrepancy before and after stabilization splint treatment. ⋯ The results suggested that TMD patients with CR-MI discrepancy showed significantly decreased brain activity in their frontal cortexes. The stabilization splint elicited functional recovery in these cortical areas. These findings provided insight into the cortical neuroplastic processes underlying TMD with CR-MI discrepancy and the therapeutic mechanisms of stabilization splint.