Search

Abstract: Electrical stimulation of the posterior dorsomedial hypothalamus (DMH) elicits a defense response, including vasodilation in the skeletal muscles and vasoconstriction in the viscera. To examine whether sympathetic premotor neurons in the rostral ventrolateral medulla (RVLM) participate in these differential vascular responses, RVLM neuron activity, renal sympathetic nerve activity (RSNA), renal vessel conductance (RVC), skeletal muscular vessel conductance (MVC), arterial pressure (AP), and heart rate (HR) were simultaneously measured in urethane-anesthetized, vagotomized, and immobilized rabbits. Electrical stimulation of the DMH increased RSNA, MVC, AP, and HR but decreased RVC. The RVLM neurons were classified into three groups according to their responses to tetanic (10s) stimulation of the DMH. Twenty neurons (Type I) were excited, 17 (Type II) were inhibited, and 2 (Type III) did not respond. To the short-train (100ms) stimulation, all of the Type I neurons showed excitation; in contrast, 12 Type II neurons showed biphasic response that was early excitation followed by inhibition. The remainder showed only inhibition. Type III neurons also did not respond to the short-train stimulation. These results indicated that regional differences in responses of sympathetic nerves in the defense response are supported by functional differentiation of sympathetic premotor neurons in the RVLM. [ABSTRACT FROM AUTHOR]

Abstract: Type 2 diabetes recently has been identified as a risk factor for developing Alzheimer''s disease (AD). The main reason for this appears to be insulin signaling failure in the brain. Furthermore, cholinergic neurons are particularly affected in the brains of AD patients. The aim of the present study is to investigate if insulin signaling-related proteins are co-located with cholinergic neuron in the CA1 region of hippocampus of mice, which could explain the early loss of cholinergic neurons in AD. Using immunohistochemistry, the insulin signaling-related proteins, such as insulin receptor (InsR), insulin receptor substrate-1 (IRS-1), protein kinase B (PKB, also named Akt), glycogen synthatase kinase-3bteta (GSK-3bteta) and insulin-degrading enzyme (IDE) were analysed. Choline acetyltransferase (ChAT) was selected as a marker of cholinergic neurons. In the CA1 region of hippocampus of mice, several of the insulin signaling-related proteins we had chosen are co-located with ChAT, and most double immunoreactive positive cells were pyramidal cells. The coexistences indicated that the insulin signaling may play an important part in the activities of cholinergic neurons, and the impairment of the pathway may be important in the mechanisms that underlie neurodegeneration in AD. [Copyright &y& Elsevier]

Abstract: LRRC4 is not only a brain-specific gene, but it has also been identified as a tumor suppressor gene for glioma. Promoter methylation of LRRC4 is frequently involved in the inactivation in glioma. MiRNA-mediated gene regulation has recently been demonstrated to play an important role in multiple biological processes related to cancer, including glioma. In this study, we demonstrated that a small regulatory microRNA, hsa-miR-381, an “oncomir”, had a major role in glioma progression and that LRRC4 was a target of hsa-miR-381. By regulating LRRC4, hsa-miR-381 increased the in vitro and in vivo proliferation of glioma cells, and this action was associated with decreased inhibition of MEK/ERK and AKT signaling. Conversely, LRRC4, as a glioma suppressor, inhibited the endogenous expression of hsa-miR-381 and decreased cell proliferation and tumor growth. The interaction of hsa-miR-381 and LRRC4 is involved in the pathogenesis of glioma. In addition, the stable expression of hsa-miR-381 in blood provides a novel and promising diagnostic biomarker, and anti-hsa-miR-381 “antagomir” may be an ideal target for glioma therapy. [Copyright &y& Elsevier]

Abstract: The α7 nicotinic acetylcholine receptors (nAChRs) play an important role in the pathophysiology of neuropsychiatric diseases such as schizophrenia and Alzheimer''s disease. However, there are currently no suitable small molecule radioligands for imaging α7 nAChRs in the brain. In this study, we synthesized the novel radioligand [125I]4-iodophenyl 1,4-diazaicyclo[3.2.2]nonane-4-carboxylate ([125I]CHIBA-1006), a iodine-derivative of the selective α7 nAChR agonist SSR180711, and studied the characterization of [125I]CHIBA-1006 binding to rat brain membranes. The assays of [125I]CHIBA-1006 binding to rat brain membranes were performed at 4°C. The presence of a single saturable high-affinity binding component for [125I]CHIBA-1006 in the rat brain was shown. Scatchard analysis revealed an apparent equilibrium dissociation constant (K d) of 88.2±21.4nM and a maximal number of binding sites (B max) of 65.4±6.8fmol/mg protein (mean±SEM, n =4). The specific binding of [125I]CHIBA-1006 was inhibited by a number of α7 nAChR-selective ligands (e.g., unlabeled CHIBA-1006, SSR180711, CHIBA-1001, MG624 and A844606), suggesting a similarity among α7 nAChR pharmacological profiles. In contrast, α-bungarotoxin, MLA, and nicotine showed very weak affinity for [125I]CHIBA-1006 binding. The regional distribution of [125I]CHIBA-1006 binding to crude membranes from dissected regions of the rat brain was different from that of [125I]α-bungarotoxin binding, suggesting that [125I]CHIBA-1006 binding sites may not be identical to [125I]α-bungarotoxin binding sites in the rat brain. The present findings suggest that [125I]CHIBA-1006 would be a useful new small molecule radioligand for α7 nAChRs in the brain. [Copyright &y& Elsevier]