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PTPRT has been known to regulate synaptic formation and dendritic arborization of hippocampal neurons. PTPRT−/− null and PTPRTD401A mutant mice displayed enhanced depression-like behaviors compared with wild-type mice. Transient knockdown of PTPRT in the dentate gyrus enhanced the depression-like behaviors of wild-type mice, whereas rescued expression of PTPRT ameliorated the behaviors of PTPRT-null mice. Chronic stress exposure reduced expression of PTPRT in the hippocampus of mice. In PTPRT deficient mice the expression of GluR2 (also known as GRIA2) was attenuated as a consequence of dysregulated tyrosine phosphorylation, and the long-term potentiation at perforant– dentate gyrus synapses was augmented. The inhibitory synaptic transmission of the dentate gyrus and hippocampal GABA concentration were reduced in PTPRT-deficient mice. In addition, the hippocampal expression of GABA transporter GAT3 (also known as SLC6A11) was decreased, and its tyrosine phosphorylation was increased in PTPRT-deficient mice. PTPRT-deficient mice displayed reduced numbers and neurite length of newborn granule cells in the dentate gyrus and had attenuated neurogenic ability of embryonic hippocampal neural stem cells. In conclusion, our findings show that the physiological roles of PTPRT in hippocampal neurogenesis, as well as synaptic functions, are involved in the pathogenesis of depressive disorder. [ABSTRACT FROM AUTHOR]

Adenomyosis is a common gynecological disorder characterized by the presence of endometrial glands and stroma deep within the myometrium associated with myometrial hypertrophy and hyperplasia. Focal uterine infarction after IVF-ET in a patient with adenomyosis following biochemical pregnancy has not been previously reported, although it occurs after uterine artery embolization in order to control symptoms caused by fibroids or adenomyosis. We report a case of a nulliparous woman who had uterine adenomyosis presenting with fever, pelvic pain and biochemical abortion after undergoing an IVF-ET procedure and the detection of a slightly elevated serum hCG. Focal uterine infarction was suspected after a pelvic magnetic resonance imaging demonstrated preserved myometrium between the endometrial cavity and inner margin of the necrotic myometrium. This case demonstrates that focal uterine infarction should be considered in the differential diagnosis of acute abdominal pain, vaginal bleeding and infectious signs in women experiencing biochemical abortion after an IVF-ET procedure. [ABSTRACT FROM AUTHOR]

Background: Two-pore domain K+ (K2P) channels have been shown to modulate neuronal excitability. However, physiological function of TWIK-1, the first identified member of the mammalian K2P channel family, in neuronal cells is largely unknown. Results: We found that TWIK-1 proteins were expressed and localized mainly in the soma and proximal dendrites of dentate gyrus granule cells (DGGCs) rather than in distal dendrites or mossy fibers. Gene silencing demonstrates that the outwardly rectifying K+ current density was reduced in TWIK-1-deficient granule cells. TWIK-1 deficiency caused a depolarizing shift in the resting membrane potential (RMP) of DGGCs and enhanced their firing rate in response to depolarizing current injections. Through perforant path stimulation, TWIK-1-deficient granule cells showed altered signal input-output properties with larger EPSP amplitude values and increased spiking compared to control DGGCs. In addition, supra-maximal perforant path stimulation evoked a graded burst discharge in 44% of TWIK-1-deficient cells, which implies impairment of EPSP-spike coupling. Conclusions: These results showed that TWIK-1 is functionally expressed in DGGCs and contributes to the intrinsic excitability of these cells. The TWIK-1 channel is involved in establishing the RMP of DGGCs; it attenuates sub-threshold depolarization of the cells during neuronal activity, and contributes to EPSP-spike coupling in perforant path-to-granule cell synaptic transmission. [ABSTRACT FROM AUTHOR]

Background: Mitochondrial trans-2-enoyl-CoA reductase (MECR) is involved in mitochondrial synthesis of fatty acids and is highly expressed in mitochondria. MECR is also known as nuclear receptor binding factor-1, which was originally reported with yeast two-hybrid screening as a binding protein of the nuclear hormone receptor peroxisome proliferator-activated receptor α (PPARα). However, MECR and PPARα are localized at different compartment, mitochondria, and the nucleus, respectively. Therefore, the presence of a cytosolic or nuclear isoform of MECR is necessary for functional interaction between MECR and PPARα. Methods: To identify the expression pattern of MECR and the cytosolic form of MECR (cMECR), we performed reverse transcription polymerase chain reaction (RT-PCR) with various tissue samples from Sprague-Dawley rats. To confirm the interaction between cMECR and PPARα, we performed several binding assays such as yeast two-hybrid, coimmunoprecipitation, and bimolecular fluorescence complementation. To observe subcellular localization of these proteins, immunocytochemistry was performed. A luciferase assay was used to measure PPARα activity. Results: We provide evidence of an alternatively spliced variant of the rat MECR gene that yields cMECR. The cMECR lacks the N-terminal 76 amino acids of MECR and shows uniform distribution in the cytoplasm and nucleus of HeLa cells. cMECR directly bound PPARα in the nucleus and increased PPARα-dependent luciferase activity in HeLa cells. Conclusion: We found the cytosolic form of MECR (cMECR) was expressed in the cytosolic and/or nuclear region, directly binds with PPARα, and enhances PPARα activity. [ABSTRACT FROM AUTHOR]

The cancer stem cell (CSC) hypothesis is predicated on the idea that not all cells have equal proliferative potential and that, in brain tumors, the cells with the greatest ability to proliferate and contribute to tumorigenesis have phenotypic and functional properties similar to normal neural stem cells (NSCs). Over the past few years, multiple investigators have shown that CSCs isolated from human brain tumors (glioma and medulloblastoma) undergo self-renewal and multilineage cell differentiation, similar to normal NSCs. In addition, CSCs from these tumors, when implanted into rodent brains, generate tumors histologically identical to the parental tumors, suggesting that progenitor/stem cells can fully recapitulate the neoplastic phenotype in vivo. While these seminal studies clearly highlight the central role of stem cells in brain tumors, they also evoke important questions regarding the importance of these unique cells to tumor initiation, maintenance and treatment. [ABSTRACT FROM AUTHOR]

The present study investigated whether thrombin, a potent microglial activator, can induce reactive oxygen species (ROS) generation through activation of microglial NADPH oxidase and if this may contribute to oxidative damage and consequent neurodegeneration. Seven days after intrahippocampal injection of thrombin, Nissl staining and immunohistochemistry using the neuronal-specific nuclear protein NeuN revealed a significant loss in hippocampal CA1 neurons. In parallel, thrombin-activated microglia, assessed by OX-42 and OX-6 immunohistochemistry, and ROS production, assessed by hydroethidine histochemistry, were observed in the hippocampal CA1 area in which degeneration of hippocampal neurons occurred. Reverse transcription-PCR at various time points after thrombin administration demonstrated an early and transient expression of inducible nitric oxide synthase (iNOS) and several proinflammatory cytokines. Western blot analysis and double-label immunohistochemistry showed an increase in the expression of and the localization of iNOS within microglia. Additional studies demonstrated that thrombin induced the upregulation of membrane (gp91phox) and cytosolic (p47phox and p67phox) components, translocation of cytosolic proteins (p47phox, p67phox, and Rac1) to the membrane, and p67phox expression of the NADPH oxidase in microglia in the hippocampus in vivo, indicating the activation of NADPH oxidase. The thrombin-induced oxidation of proteins and loss of hippocampal CA1 neurons were partially inhibited by an NADPH oxidase inhibitor and by an antioxidant. To our knowledge, the present study is the first to demonstrate that thrombin-induced neurotoxicity in the hippocampus in vivo is caused by microglial NADPH oxidase-mediated oxidative stress. This suggests that thrombin inhibition or enhancing antioxidants may be beneficial for the treatment of neurodegenerative diseases, such as Alzheimer's disease,... [ABSTRACT FROM AUTHOR]