内脏高敏感是肠易激综合征慢性疼痛的重要发病机制。精神应激既是肠易激综合征发病的诱因,同时也调控大脑各脑区脑源性神经营养因子的表达水平。在精神应激动物模型中,脑源性神经营养因子(BDNF)可通过与高亲和力受体TrkB结合,改变MAPK/ERK,CaMK、PI3K/Akt等信号通路关键分子表达,同时伴多个脑区突触可塑性改变,而内脏痛觉传导通路相关脑区突触可塑性改变与内脏高敏感形成相关。文章就BDNF与精神应激诱发内脏高敏感相关性作一综述。
Visceral hypersensitivity is the important pathogenic mechanism of irritable bowel syndrome.Psychogenic stress is not only the cause of irritable bowel syndrome,but also a regulator of the expression of brain-derived neurotrophic factor (BDNF) in brain regions.In animal models of psychogenic stress,BDNF regulates MAPK/ERK,CaMK,and PI3K/Akt signal pathways through combining with high affinity nerve growth factor receptor TrkB and is accompanied with the change of synaptic plasticity in many brain regions associated with the formation of visceral hypersensitivity.Here,we reviewed the relationship between BDNF and visceral hypersensitivity induced by psychogenic stress.
[1] Merighi A,Salio C,Ghirri A,et al.BDNF as a pain modulator[J].Prog Neurobiol,2008,85(3):297-317.
[2] Lu J,Wu Y,Sousa N,et al.SMAD pathway mediation of BDNF and TGF beta 2 regulation of proliferation and differentiation of hippocampal granule neurons[J].Development,2005,132(14):3231-3242.
[3] Karpova NN.Role of BDNF epigenetics in activity-dependent neuronal plasticity[J].Neuropharmacology,2014,76 (part C):709-718
[4] Numakawa T,Suzuki S,Kumamaru E,et al.BDNF function and intracellular signaling in neurons[J].Histol Histopathol,2010,25(2):237-258.
[5] Ninan I.Synaptic regulation of affective behaviors;role of BDNF[J].Neuropharmacology,2014,76(2):684-695
[6] Minichiello L,Calella AM,Medina DL,et al.Mechanism of TrkB-mediated hippocampal long-term potentiation[J].Neuron,2002,36(1):121-137.
[7] Pang PT,Lu B.Regulation of late-phase LTP and long-term memory in normal and aging hippocampus:role of secreted proteins tPA and BDNF[J].Ageing Res Rev,2004,3(4):407-430.
[8] Wang J,Zhang X,Cao B,et al.Facilitation of synaptic transmission in the anterior cingulate cortex in viscerally hypersensitive rats[J].Cereb Cortex,2015,25(4):859-868.
[9] Chen Y,Chen A Q,Luo X Q,et al.Hippocampal NR2B-containing NMDA receptors enhance long-term potentiation in rats with chronic visceral pain[J].Brain Res,2014,1570:43-53.
[10] Zheng Z,Zeng Y,Yang W,et al.Irritable bowel syndrome may be induced by decreased neuroplasticity[J].Neuro Endocrinol Lett,2014,35(8):655-665.
[11] Blugeot A,Rivat C,Bouvier E,et al.Vulnerability to depression:from brain neuroplasticity to identification of biomarkers[J].J Neurosci,2011,31(36):12889-12899.
[12] Chung EK,Bian ZX,Xu HX,et al.Neonatal maternal separation increases brain-derived neurotrophic factor and tyrosine kinase receptor B expression in the descending pain modulatory system[J].Neurosignals,2009,17(3):213-221.
[13] O′Sullivan E,Barrett E,Grenham S,et al.BDNF expression in the hippocampus of maternally separated rats:does Bifidobacterium breve 6330 alter BDNF levels?[J].Benef Microbes,2011,2(3):199-207.
[14] Quan X,Luo H,Fan H,et al.Brain-derived neurotrophic factor contributes to colonic hypermotility in a chronic stress rat model[J].Dig Dis Sci,2015,60(8):2316-2326.
[15] Kumamaru E,Numakawa T,Adachi N,et al.Glucocorticoid prevents brain-derived neurotrophic factor-mediated maturation of synaptic function in developing hippocampal neurons through reduction in the activity of mitogen-activated protein kinase[J].Mol Endocrinol,2008,22(3):546-558.
[16] Zheng Z,Zeng Y and Wu J.Increased neuroplasticity may protect against cardiovascular disease[J].Int J Neurosci,2013,123(9):599-608.
[17] Moloney RD,Dinan TG,Cryan JF.Strain-dependent variations in visceral sensitivity:relationship to stress,anxiety and spinal glutamate transporter expression[J].Genes Brain Behav,2015,14(4):319-329.
[18] Yu Y,Wu S,Li J,et al.The effect of curcumin on the brain-gut axis in rat model of irritable bowel syndrome:involvement of 5-HT-dependent signaling[J].Metab Brain Dis,2015,30(1):47-55.