不同浓度降钙素基因相关肽对小鼠海马区长时程增强的影响
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摘要
本研究旨在探讨不同浓度的降钙素基因相关肽(calcitonin gene-related peptide,CGRP)对小鼠海马长时程增强的影响。将30日龄C57BL/6J小鼠随机分为空白组、不同浓度(50,100,200 nmol/L)CGRP组,CGRP+CGRP阻断剂组,每组10只。外源性给予海马区脑片不同浓度的CGRP,用离体细胞外场电位记录检测其对小鼠海马突触传递及长时程增强的影响。结果显示,给予不同浓度CGRP对小鼠海马突触前递质的释放没有明显的影响,但100和200 nmol/L CGRP可易化海马长时程增强的诱发,表现为长时程增强幅度的增加,并且这一作用可被CGRP特异性阻断剂CGRP8-37阻断。以上结果提示,CGRP可通过特异性受体浓度依赖性促进小鼠海马长时程增强的诱发。
The purpose of this study was to explore the effects of different concentrations of calcitonin gene-related peptide(CGRP) on long-term potentiation(LTP) in the hippocampus of mice. C57 BL/6 J mice(30 days old) were randomly divided into control group, three CGRP groups, and CGRP + CGRP_(8-37) group(10 mice for each group). Different concentrations of CGRP(50, 100 and 200 nmol/L) were given to the hippocampal slices of mice. The presynaptic release of neurotransmitters and the induction of LTP were measured by extracellular field recording techniques. The result showed that different concentrations of CGRP did not affect the presynaptic release of neurotransmitters, but 100 and 200 nmol/L CGRP increased the amplitude of LTP induced in the hippocampus of mice. This facilitation effect of CGRP was blocked by its specific antagonist CGRP_(8-37). These results suggest that CGRP dose-dependently facilitates the induction of LTP in the hippocampus of mice through its specific receptor.
The purpose of this study was to explore the effects of different concentrations of calcitonin gene-related peptide(CGRP) on long-term potentiation(LTP) in the hippocampus of mice. C57 BL/6 J mice(30 days old) were randomly divided into control group, three CGRP groups, and CGRP + CGRP_(8-37) group(10 mice for each group). Different concentrations of CGRP(50, 100 and 200 nmol/L) were given to the hippocampal slices of mice. The presynaptic release of neurotransmitters and the induction of LTP were measured by extracellular field recording techniques. The result showed that different concentrations of CGRP did not affect the presynaptic release of neurotransmitters, but 100 and 200 nmol/L CGRP increased the amplitude of LTP induced in the hippocampus of mice. This facilitation effect of CGRP was blocked by its specific antagonist CGRP_(8-37). These results suggest that CGRP dose-dependently facilitates the induction of LTP in the hippocampus of mice through its specific receptor.
引文
1 Rosenfeld MG,Mermod JJ,Amara SG,Swanson LW,Sawchenko PE,Rivier J,Vale WW,Evans RM.Production of a novel neuropeptide encoded by the calcitonin gene via tissue-specific RNA processing.Nature 1983;304(5922):129-135.
2 Russell FA,King R,Smillie SJ,Kodji X,Brin SD.Calcitonin gene-related peptide:physiology and pathophysiology.Physiol Rev 2014;94(4):1099-1142.
3 Liu XD,Zhang JJ,Wang Y,Yu LC.Inhibitory effects of calcitonin gene-related peptide on long-term potentiation induced in hippocampal slices of rats.Neurosci Lett 2011;494(1):10-13.
4 Sink KS,Walker DL,Yang Y,Davis M.Calcitonin generelated peptide in the bed nucleus of the stria terminalis produces an anxiety-like pattern of behavior and increases neural activation in anxiety-related structures.J Neurosci2011;31(5):1802-1810.
5 Ruiz G,Banos JE.The effect of endoneurial nerve growth factor on calcitonin gene-related peptide expression in primary sensory neurons.Brain Res 2005;1042(1):44-52.
6 Holland JP,Sydserff SG,Taylor WA,Bell BA.Calcitonin gene-related peptide reduces brain injury in a rat model of focal cerebral ischemia.Stroke 1994;25(10):2055-2059.
7 Pittman SK,Gracisa NG,Fehrenbacher JC.Nerve growth factor alters microtubule targeting agent-induced neurotransmitter release but not MTA-induced neurite retraction in sensory neurons.Exp Neurol 2016;279:104-115.
8 Hashikawa-Hobara N,Ogawa T,Sakamoto Y,Matsuo Y,Ogawa M,Zamami Y,Hashikawa N.Calcitonin gene-related peptide pre-administration acts as a novel antidepressant in stressed mice.Sci Rep 2015;5:12559.
9 Wu X(武鑫),Zheng WJ,Lv MH,Gao JF.Effect of bilateral injection of calcitonin gene-related peptide into amygdala on learning and memory of mice.Acta Physiol Sin(生理学报)2017;69(2):167-171(in Chinese with English abstract).
10 Nicoll RA,Schmitz D.Synaptic plasticity at hippocampal mossy fiber synapses.Nat Rev Neurosci 2005;6(11):863-876.
11 Sweatt JD.Neural plasticity and behavior-sixty years of conceptual advances.J Neurochem 2016;139 Suppl 2:179-199.
12 Poncer JC.Hippocampal long term potentiation:silent synapses and beyond.J Physiol Paris 2003;97(4-6):415-422.
13 Shema R,Sacktor TC,Dudai Y.Rapid erasure of long-term memory associations in the cortex by an inhibitor of PKMzeta.Science 2007;317(5840):951-953.
14 Aiyar N,Rand K,Elshourbagy NA,Zeng Z,Adamou JE,Bergsma DJ,Li Y.A c DNA encoding the calcitonin generelated peptide type 1 receptor.J Biol Chem 1996;271(19):11325-11329.
15 Tu S,Okamoto S,Lipton SA,Xu H.Oligometric Aβ-induced synaptic dysfunction in Alzheimer’s disease.Mol Neurodegener 2014;9:48.
16 Chong SA,Benilova I,Shaban H,De Strooper B,Devijver H,Moechars D,Eberle W,Bartic C,Van Leuven F,Callewaert G.Synaptic dysfunction in hippocampus of transgenic mouse models of Alzheimer’s disease:a multi-electrode array study.Neurobiol Dis 2011;44(3):284-291.
2 Russell FA,King R,Smillie SJ,Kodji X,Brin SD.Calcitonin gene-related peptide:physiology and pathophysiology.Physiol Rev 2014;94(4):1099-1142.
3 Liu XD,Zhang JJ,Wang Y,Yu LC.Inhibitory effects of calcitonin gene-related peptide on long-term potentiation induced in hippocampal slices of rats.Neurosci Lett 2011;494(1):10-13.
4 Sink KS,Walker DL,Yang Y,Davis M.Calcitonin generelated peptide in the bed nucleus of the stria terminalis produces an anxiety-like pattern of behavior and increases neural activation in anxiety-related structures.J Neurosci2011;31(5):1802-1810.
5 Ruiz G,Banos JE.The effect of endoneurial nerve growth factor on calcitonin gene-related peptide expression in primary sensory neurons.Brain Res 2005;1042(1):44-52.
6 Holland JP,Sydserff SG,Taylor WA,Bell BA.Calcitonin gene-related peptide reduces brain injury in a rat model of focal cerebral ischemia.Stroke 1994;25(10):2055-2059.
7 Pittman SK,Gracisa NG,Fehrenbacher JC.Nerve growth factor alters microtubule targeting agent-induced neurotransmitter release but not MTA-induced neurite retraction in sensory neurons.Exp Neurol 2016;279:104-115.
8 Hashikawa-Hobara N,Ogawa T,Sakamoto Y,Matsuo Y,Ogawa M,Zamami Y,Hashikawa N.Calcitonin gene-related peptide pre-administration acts as a novel antidepressant in stressed mice.Sci Rep 2015;5:12559.
9 Wu X(武鑫),Zheng WJ,Lv MH,Gao JF.Effect of bilateral injection of calcitonin gene-related peptide into amygdala on learning and memory of mice.Acta Physiol Sin(生理学报)2017;69(2):167-171(in Chinese with English abstract).
10 Nicoll RA,Schmitz D.Synaptic plasticity at hippocampal mossy fiber synapses.Nat Rev Neurosci 2005;6(11):863-876.
11 Sweatt JD.Neural plasticity and behavior-sixty years of conceptual advances.J Neurochem 2016;139 Suppl 2:179-199.
12 Poncer JC.Hippocampal long term potentiation:silent synapses and beyond.J Physiol Paris 2003;97(4-6):415-422.
13 Shema R,Sacktor TC,Dudai Y.Rapid erasure of long-term memory associations in the cortex by an inhibitor of PKMzeta.Science 2007;317(5840):951-953.
14 Aiyar N,Rand K,Elshourbagy NA,Zeng Z,Adamou JE,Bergsma DJ,Li Y.A c DNA encoding the calcitonin generelated peptide type 1 receptor.J Biol Chem 1996;271(19):11325-11329.
15 Tu S,Okamoto S,Lipton SA,Xu H.Oligometric Aβ-induced synaptic dysfunction in Alzheimer’s disease.Mol Neurodegener 2014;9:48.
16 Chong SA,Benilova I,Shaban H,De Strooper B,Devijver H,Moechars D,Eberle W,Bartic C,Van Leuven F,Callewaert G.Synaptic dysfunction in hippocampus of transgenic mouse models of Alzheimer’s disease:a multi-electrode array study.Neurobiol Dis 2011;44(3):284-291.