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Anhui Medical and Pharmaceutical Journal 2017 Oct, 21(10) 1757 活,增加AMPK的激活,后者是 tORO1信号通路 学进展,2008,8(11):21292131 和突触蛋白合成的关键调节因子的。 5] KOENIGS M. Distinct regions of prefrontal cortex mediate resist 在小鼠脑内特异性地敲除胰岛素受体,线粒体 ance and vulnerability to depression []. J Neurosci,2008,28 (47):12341-2348 功能失调,脑内的单胺代谢失衡,引起小鼠的焦虑 PRICE JI, DREVETS WC. Neurocircuitry of Mood Disorders Dj 和抑郁样的表现。高脂饮食诱导的糖尿病及胰 Neuropsychopharmacology, 2010, 35(1): 192-216 岛素抵抗会导致皮质和边缘结构的神经元凋亡,减 BOES AD, MCCORMICK LM, CORYELL WH,tal. Rostral ante. 少突触的可塑性。发达国家的抑郁症和糖尿 rior cingulate cortex volume correlates with depressed mood in nor- 病、肥胖的高共发率部分原因来自于胰岛素抵抗, mal healthy children [. Biol Psychiatry, 2008, 63(4): 391-397. 由于存在着异常的能量代谢及能量运送至脑的方 8] HIRAYASU Y, SHENTON ME, SALISBURY DF, et al. Subgenual cingulate cortex volume in first-pisode psychosis [. Am J Psychi 式,疾病被肾上腺糖皮质激素和炎性细胞因子的破 atry,199,156(7):10914093 坏性作用加剧。相反,运动会产生有益的因子,增] PEZAWAS L, MEYER-INDENBERG A, DRABANT EM,cl.5 加BDNF、 mTRC1信号传导和肌源性因子表达,提 HTTLPR polymorphism impacts human cingulate amygdala inter- 高神经可塑性,可对慢性压力产生抵抗的 ctions:a genetic susceptibility mechanism for depression [.Nat Neurosci,2005,8(6):828-34. 循环肽,包括来自脂肪组织的瘦素、脂联素和 uo DREVETS WC, BOGERS W. RAICHLE ME. Functional anatomi- 来自于胃的饥饿素,可以影响饮食行为和能量稳 al correlates of antidepressant drug treatment assessed using PET 态,也同样可被压力所调节,并影响啮齿动物的抑 measures of regional glucose metabolism []. Eur Neuropsycho- 郁和焦虑的行为。饮食、能量稳态、内分泌系统 (6):527544 和神经内分泌系统同样受到肠道微生物的影响,失 [1] PIZZAGALLI D, PASCUAL-MARQUI RD, NITSCHKE JB, et al Anterior cingulate activity as a predictor of degree of treatment 衡的脑肠轴会引起抑郁和焦虑 3小结 graphy analysis [I. Am J Psychiatry 2001, 158(3): 405-415 目前对抑郁症发病机制公认的观点有:(1)易患02] DREVETS WC. Functional neuroimaging studies of depressie:the 基因和压力对抑郁症的发生至关重要;(2)HPA轴功 anatomy of melancholia [. Annu Rev Med, 1998,49: 341361 能紊乱会减少抑郁症患者海马区的体积和前额皮层 [3] WALLIS JD. Crossspecies studies of orbitofrontal cortex and val- PC的活性,破坏抑郁症患者神经环路的稳态;(3)040N0RD. FERRY AT, PRICE JI. Architectonic subdivision of 抗抑郁药物可增加脑源性的神经营养,恢复神经元的 he human orbital and medial prefrontal cortex [I J Comp Neu- 可塑性,调节神经环路各结构的相互作用。 rol,2003,460(3):425449 由于脑部结构的复杂性及神经通路的混杂性 [15] ZHANG XC, DI X, LEI H, et al. Imbalanced spontaneous brain 仍然有大量的问题亟待解释。例如,抑郁症患者海 tivity in orbitofrontal-insular circuits in individuals with cognitive vulnerability to depression [. J Affect Disord, 2016,198: 56-463 马区和PC脑容量的改变在缺少压力和HPA轴异61xUc,MAxM, CHEN HE,etal. Orbitofrontal cortex 5+m2A 常的情况下是否能发生?白质在抑郁症的发生中 ceptor mediates chronic stress-induced depressivedike behaviors 起到了怎样的作用?此外,对神经可塑性是否是抑 and alterations of spine density and Kalirin7 [. Neuropharmacol 郁症的重要影响因素仍存在争议。为了解决上述 qgy,2016,109:7+7 问题,需要更多的实验数据作为支持。 07 VARGA Z, CSABAI D, MISETA A, et al. Chronic stress affects the number of GAbaergic in the orbitofrontal cortex of rats L. Behav Brain Res, 2017,316: 10414 参考文献 18] VIDAL-GONZALEZ I, VIDAL-GONZALEZ B, RAUCH SL, et al [] PRICE JL, DREVETS WC. Neural circuits underlying the pathophysi- Microstimulation reveals opposing influences of prelimbic and ology of mood disorders [l. Trends Cogn Sci, 2012, 16(1): 61 fralimbie cortex on the expression of conditioned fear [].Learn 22] RIDDERINKHOF KR, WILDENBERG WPM, SEGALOWITZ SJ Mem,2006,13(6):728=33. et al. Neurocognitive mechanisms of cognitive control the role of 09] PRICE JL Free will versus survival: brain systems that underlie intrin- prefrontal cortex in action selection, response inhibition, perform- ic constraints on behavior [. J Comp Neurol. 2005,493: 132-139 e monitoring, and reward-based leaming []. Brain Cogn [20] DUMAN RS, AGHAJANIAN GK, SANACORA G, et al. Synaptic 2004,56(2):129140. plasticity and depression: new insights from stress and rapid-acting B] KOENIGS M, GRAFMAN J. The functional neuroanatomy of de antidepressants [. Nat Med, 2016,22(3): 238-249 pression: Distinct roles for ventromedial and dorsolateral prefrontal [21] ROOZENDAAL B, MCEWEN BS, CHATTARJI S. Stress, memory cortex [l Behav Brain Res, 2009, 201(2): 239243 and the amygdala []. Nat Rev Neurosci, 2009, 10(6): 423-433 [4]李稳,余细连,张力内侧前额叶与社会认知].现代生物医22] DREVETS WC, PRICE JL, FUREY ML Brain structural and function 21994-2017ChinaAcademicJOurnalElectronicpUblishingHouse.Allrightsreservedhttp:/www.cnki.net活,增加 AMPK 的激活,后者是 mTORC1 信号通路 和突触蛋白合成的关键调节因子[69]。 在小鼠脑内特异性地敲除胰岛素受体,线粒体 功能失调,脑内的单胺代谢失衡,引起小鼠的焦虑 和抑郁样的表现[84]。高脂饮食诱导的糖尿病及胰 岛素抵抗会导致皮质和边缘结构的神经元凋亡,减 少突触的可塑性[85-86]。发达国家的抑郁症和糖尿 病、肥胖的高共发率部分原因来自于胰岛素抵抗, 由于存在着异常的能量代谢及能量运送至脑的方 式,疾病被肾上腺糖皮质激素和炎性细胞因子的破 坏性作用加剧。相反,运动会产生有益的因子,增 加 BDNF、mTORC1 信号传导和肌源性因子表达,提 高神经可塑性,可对慢性压力产生抵抗[87-88]。 循环肽,包括来自脂肪组织的瘦素、脂联素和 来自于胃的饥饿素,可以影响饮食行为和能量稳 态,也同样可被压力所调节,并影响啮齿动物的抑 郁和焦虑的行为[89]。饮食、能量稳态、内分泌系统 和神经内分泌系统同样受到肠道微生物的影响,失 衡的脑肠轴会引起抑郁和焦虑。 3 小结 目前对抑郁症发病机制公认的观点有: ( 1) 易患 基因和压力对抑郁症的发生至关重要; ( 2) HPA 轴功 能紊乱会减少抑郁症患者海马区的体积和前额皮层 PFC 的活性,破坏抑郁症患者神经环路的稳态; ( 3) 抗抑郁药物可增加脑源性的神经营养,恢复神经元的 可塑性,调节神经环路各结构的相互作用[90]。 由于脑部结构的复杂性及神经通路的混杂性, 仍然有大量的问题亟待解释。例如,抑郁症患者海 马区和 PFC 脑容量的改变在缺少压力和 HPA 轴异 常的情况下是否能发生? 白质在抑郁症的发生中 起到了怎样的作用? 此外,对神经可塑性是否是抑 郁症的重要影响因素仍存在争议。为了解决上述 问题,需要更多的实验数据作为支持。 参考文献 [1] PRICE JL,DREVETS WC. Neural circuits underlying the pathophysi￾ology of mood disorders[J]. Trends Cogn Sci,2012,16( 1) : 61-71. [2] RIDDERINKHOF KR,WILDENBERG WPM,SEGALOWITZ SJ, et al. Neurocognitive mechanisms of cognitive control: the role of prefrontal cortex in action selection,response inhibition,perform￾ance monitoring,and reward-based learning[J]. Brain Cogn, 2004,56( 2) : 129-140. [3] KOENIGS M,GRAFMAN J. The functional neuroanatomy of de￾pression: Distinct roles for ventromedial and dorsolateral prefrontal cortex[J]. Behav Brain Res,2009,201( 2) : 239-243. [4] 李稳,余细连,张力. 内侧前额叶与社会认知[J]. 现代生物医 学进展,2008,8( 11) : 2129-2131. [5] KOENIGS M. Distinct regions of prefrontal cortex mediate resist￾ance and vulnerability to depression[J]. J Neurosci,2008,28 ( 47) : 12341-12348. [6] PRICE JL,DREVETS WC. Neurocircuitry of Mood Disorders[J]. Neuropsychopharmacology,2010,35( 1) : 192-216. [7] BOES AD,MCCORMICK LM,CORYELL WH,et al. Rostral ante￾rior cingulate cortex volume correlates with depressed mood in nor￾mal healthy children[J]. Biol Psychiatry,2008,63( 4) : 391-397. [8] HIRAYASU Y,SHENTON ME,SALISBURY DF,et al. Subgenual cingulate cortex volume in first-episode psychosis[J].Am J Psychi￾atry,1999,156( 7) : 1091-1093. [9] PEZAWAS L,MEYER-LINDENBERG A,DRABANT EM,et al. 5- HTTLPR polymorphism impacts human cingulate-amygdala inter￾actions: a genetic susceptibility mechanism for depression[J]. Nat Neurosci,2005,8( 6) : 828-834. [10] DREVETS WC,BOGERS W,RAICHLE ME. Functional anatomi￾cal correlates of antidepressant drug treatment assessed using PET measures of regional glucose metabolism[J]. Eur Neuropsycho￾pharmacol,2002,12( 6) : 527-544. [11] PIZZAGALLI D,PASCUAL-MARQUI RD,NITSCHKE JB,et al. Anterior cingulate activity as a predictor of degree of treatment re￾sponse in major depression: evidence from brain electrical tomo￾graphy analysis[J]. Am J Psychiatry,2001,158( 3) : 405-415. [12] DREVETS WC. Functional neuroimaging studies of depression: the anatomy of melancholia[J]. Annu Rev Med,1998,49: 341-361. [13] WALLIS JD. Cross-species studies of orbitofrontal cortex and val￾ue-based decision-making[J]. Nat Neurosci,2012,15( 1) : 13-19. [14] ONGR D,FERRY AT,PRICE JL. Architectonic subdivision of the human orbital and medial prefrontal cortex[J]. J Comp Neu￾rol,2003,460( 3) : 425-449. [15] ZHANG XC,DI X,LEI H,et al. Imbalanced spontaneous brain ac￾tivity in orbitofrontal-insular circuits in individuals with cognitive vulnerability to depression[J]. J Affect Disord,2016,198: 56-63. [16] XU C,MA XM,CHEN HB,et al. Orbitofrontal cortex 5-HT2A re￾ceptor mediates chronic stress-induced depressive-like behaviors and alterations of spine density and Kalirin7[J]. Neuropharmacol￾ogy,2016,109: 7-17. [17] VARGA Z,CSABAI D,MISETA A,et al. Chronic stress affects the number of GABAergic neurons in the orbitofrontal cortex of rats [J]. Behav Brain Res,2017,316: 104-114. [18] VIDAL-GONZALEZ I,VIDAL-GONZALEZ B,RAUCH SL,et al. Microstimulation reveals opposing influences of prelimbic and in￾fralimbic cortex on the expression of conditioned fear[J]. Learn Mem,2006,13( 6) : 728-733. [19] PRICE JL. Free will versus survival: brain systems that underlie intrin￾sic constraints on behavior[J]. J Comp Neurol,2005,493: 132-139. [20] DUMAN RS,AGHAJANIAN GK,SANACORA G,et al. Synaptic plasticity and depression: new insights from stress and rapid-acting antidepressants[J]. Nat Med,2016,22( 3) : 238-249. [21] ROOZENDAAL B,MCEWEN BS,CHATTARJI S. Stress,memory and the amygdala[J]. Nat Rev Neurosci,2009,10( 6) : 423-433. [22] DREVETS WC,PRICE JL,FUREY ML. Brain structural and function- 安 徽 医 药 Anhui Medical and Pharmaceutical Journal 2017 Oct,21( 10) ·1757·
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