Alpha1-Adrenoceptor Antagonists Improve Memory by Activating N-Methyl-D-Aspartate-Induced Ion Currents in the Rat Hippocampus
2
조회
0
다운로드
3
인용
0
참고문헌
키워드
초록
Purpose: Alpha1 (α1)-adrenoceptor antagonists are widely used to treat lower urinary tract symptoms. These drugs not only act on peripheral tissues, but also cross the blood-brain barrier and affect the central nervous system. Therefore, α1- adrenoceptor antagonists may enhance brain functions. In the present study, we investigated the effects of tamsulosin, an α1- adrenoceptor antagonist, on short-term memory, as well as spatial learning and memory, in rats. Methods: The step-down avoidance test was used to evaluate short-term memory, and an eight-arm radial maze test was used to evaluate spatial learning and memory. TUNEL (terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling) staining was performed in order to evaluate the effect of tamsulosin on apoptosis in the hippocampal dentate gyrus. Patch clamp recordings were used to evaluate the effect of tamsulosin on ionotropic glutamate receptors, such as N-methyl-D-aspartate (NMDA), amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA), and kainate receptors, in hippocampal CA1 neurons. Results: Tamsulosin treatment improved short-term memory, as well as spatial learning and memory, without altering apoptosis. The amplitudes of NMDA-induced ion currents were dose-dependently increased by tamsulosin. However, the amplitudes of AMPA- and kainate-induced ion currents were not affected by tamsulosin. Conclusions: Tamsulosin enhanced memory function by activating NMDA receptor-mediated ion currents in the hippocampus without initiating apoptosis. The present study suggests the possibility of using tamsulosin to enhance memory under normal conditions, in addition to its use in treating overactive bladder.
Abstract
Purpose: Alpha1 (α1)-adrenoceptor antagonists are widely used to treat lower urinary tract symptoms. These drugs not only act on peripheral tissues, but also cross the blood-brain barrier and affect the central nervous system. Therefore, α1- adrenoceptor antagonists may enhance brain functions. In the present study, we investigated the effects of tamsulosin, an α1- adrenoceptor antagonist, on short-term memory, as well as spatial learning and memory, in rats. Methods: The step-down avoidance test was used to evaluate short-term memory, and an eight-arm radial maze test was used to evaluate spatial learning and memory. TUNEL (terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling) staining was performed in order to evaluate the effect of tamsulosin on apoptosis in the hippocampal dentate gyrus. Patch clamp recordings were used to evaluate the effect of tamsulosin on ionotropic glutamate receptors, such as N-methyl-D-aspartate (NMDA), amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA), and kainate receptors, in hippocampal CA1 neurons. Results: Tamsulosin treatment improved short-term memory, as well as spatial learning and memory, without altering apoptosis. The amplitudes of NMDA-induced ion currents were dose-dependently increased by tamsulosin. However, the amplitudes of AMPA- and kainate-induced ion currents were not affected by tamsulosin. Conclusions: Tamsulosin enhanced memory function by activating NMDA receptor-mediated ion currents in the hippocampus without initiating apoptosis. The present study suggests the possibility of using tamsulosin to enhance memory under normal conditions, in addition to its use in treating overactive bladder.
참고문헌 (35)
- Abrams P, "Describing bladder storage function: overactive bladder syndrome and detrusor overactivity", Urology, 62(5 Suppl 2), pp.28~37 (2003)
- Chu FM, "Pathophysiology of overactive bladder", Am J Med, 119(3 Suppl 1), pp.3~8 (2006)
- Andersson KE, "Pharmacotherapy of the overactive bladder", Discov Med, 8, pp.118~124 (2009)
- Athanasopoulos A, "Combination treatment with an alpha-blocker plus an anticholinergic for bladder outlet obstruction: a prospective, randomized, controlled study", J Urol, 169, pp.2253~2256 (2003)
- Barendrecht MM, "Do alpha1-adrenoceptor antagonists improve lower urinary tract symptoms by reducing bladder outlet resistance", Neurourol Urodyn, 27, pp.226~230 (2008)
- Tikhonov DB, "Origin and molecular evolution of ionotropic glutamate receptors", Neurosci Behav Physiol, 39, pp.763~773 (2009)
- Dietrich MO, "Exercise affects glutamate receptors in postsynaptic densities from cortical mice brain", Brain Res, 1065, pp.20~25 (2005)
- Dong Z, "Long-term potentiation decay and memory loss are mediated by AMPAR endocytosis", J Clin Invest, 125, pp.234~247 (2015)
- Lowry ER, "The GluK4 kainate receptor subunit regulates memory, mood, and excitotoxic neurodegeneration", Neuroscience, 235, pp.215~225 (2013)
- Vasuta C, "Effects of exercise on NMDA receptor subunit contributions to bidirectional synaptic plasticity in the mouse dentate gyrus", Hippocampus, 17, pp.1201~1208 (2007)
- Jansson LC, "The role of glutamate and its receptors in the proliferation, migration, differentiation and survival of neural progenitor cells", J Neural Transm (Vienna), 121, pp.819~836 (2014)
- Karakas E, "Emerging structural insights into the function of ionotropic glutamate receptors", Trends Biochem Sci, 40, pp.328~337 (2015)
- Xie M, "Short-term sleep deprivation impairs spatial working memory and modulates expression levels of ionotropic glutamate receptor subunits in hippocampus", Behav Brain Res, 286, pp.64~70 (2015)
- Thompson CB, "Apoptosis in the pathogenesis and treatment of disease", Science, 267, pp.1456~1462 (1995)
- Suh HJ, "Neuroprotective effects of tamsulosin on intracerebral hemorrhage", Neural Regen Res, 6, pp.2505~2510 (2011)
- Gavrieli Y, "Identification of programmed cell death in situ via specific labeling of nuclear DNA fragmentation", J Cell Biol, 119, pp.493~501 (1992)
- 김성은, "Effects of Tamsulosin on Urinary Bladder Function and Neuronal Activity in the Voiding Centers of Rats with Cyclophosphamide-induced Overactive Bladder", International Neurourology Journal, 16(1), pp.13~22 (2012), 대한배뇨장애요실금학회
- Giuliano F, "Impact of medical treatments for benign prostatic hyperplasia on sexual function", BJU Int, 97(Suppl 2), pp.34~38 (2006)
- 전정원, "Adenosine A2A-receptor agonist polydeoxyribonucleotide promotes gastric ulcer healing in Mongolian gerbils", Animal Cells and Systems, 18(6), pp.399~406 (2014), 한국통합생물학회[DOI]
- 조한샘, "Treadmill exercise alleviates short-term memory impairment in 6-hydroxydopamine-induced Parkinson’s rats", Journal of exercise rehabilitation, 9(3), pp.354~361 (2013), 한국운동재활학회[DOI]
- 서태범, "Treadmill exercise improves behavioral outcomes and spatial learning memory through up-regulation of reelin signaling pathway in autistic rats", Journal of exercise rehabilitation, 9(2), pp.220~229 (2013), 한국운동재활학회[DOI]
- Ko IG, "Tadalafil improves short-term memory by suppressing ischemiainduced apoptosis of hippocampal neuronal cells in gerbils", Pharmacol Biochem Behav, 91, pp.629~635 (2009)
- Kim Y, "Modulation of Chelidonii herba on GABA activated chloride current in rat PAG neurons", Am J Chin Med, 29, pp.265~279 (2001)
- Yang HJ, "Bupivacaine and ropivacaine suppress glycine- and glutamate-induced ion currents in acutely dissociated rat hippocampal neurons", Neurosci Lett, 344, pp.33~36 (2003)
- Price D, "Potential mechanisms of action of superselective alpha(1)- adrenoceptor antagonists", Eur Urol, 40(Suppl 4), pp.5~11 (2001)
- Gibbs ME, "Stimulation of alpha1-adrenoceptors inhibits memory consolidation in the chick", Eur J Neurosci, 14, pp.1369~1376 (2001)
- Zuscik MJ, "Overexpression of the alpha1B-adrenergic receptor causes apoptotic neurodegeneration: multiple system atrophy", Nat Med, 6, pp.1388~1394 (2000)
- Giorgi FS, "The role of norepinephrine in epilepsy: from the bench to the bedside", Neurosci Biobehav Rev, 28, pp.507~524 (2004)
- Scheiderer CL, "Novel form of longterm synaptic depression in rat hippocampus induced by activation of alpha 1 adrenergic receptors", J Neurophysiol, 91, pp.1071~1077 (2004)
- Lapiz MD, "Noradrenergic modulation of cognitive function in rat medial prefrontal cortex as measured by attentional set shifting capability", Neuroscience, 137, pp.1039~1049 (2006)
- Arnsten AF, "Alpha-1 noradrenergic receptor stimulation impairs prefrontal cortical cognitive function", Biol Psychiatry, 45, pp.26~31 (1999)
- 한진희, "Dexmedetomidine, α2-adrenoceptor agonist, does not induce apoptosis in the brachial plexus of rats", Animal Cells and Systems, 18(6), pp.407~415 (2014), 한국통합생물학회[DOI]
- Hudspith MJ, "Glutamate: a role in normal brain function, anaesthesia, analgesia and CNS injury", Br J Anaesth, 78, pp.731~747 (1997)
- 박준기, "Treadmill exercise enhances NMDA receptor expression in schizophrenia mice", Journal of exercise rehabilitation, 10(1), pp.15~21 (2014), 한국운동재활학회[DOI]
- Dai Y, "Effects of uterine and lactational exposure to di-(2-ethylhexyl) phthalate on spatial memory and NMDA receptor of hippocampus in mice", Horm Behav, 71, pp.41~48 (2015)