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小清蛋白中间神经元损伤可能是精神分裂症发生发展的中心环节
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Abstract:
小清蛋白中间神经元(parvalbumin interneuron, PVI)是一种具有长期发育轨迹的神经元群体，容易受到出生后危险因素的影响和伤害。本文系统复习了可能导致PVI损伤的危险因素，包括多巴胺能系统亢进、NMDA受体被阻断和氧化应激。这些因素均在精神分裂症的疾病发生中起重要作用。损伤的PVI对其下游的神经元活动调控障碍，使中脑腹侧被盖区多巴胺能神经元去抑制因而皮层多巴胺释放增加、谷氨酸脱抑制性释放产生兴奋性神经毒性、并影响少突胶质前体细胞(OPC)发育和成熟因而出现髓鞘化障碍。通过这些途径，PVI损伤影响脑高级功能活动，包括认知、情感和社会功能障碍。
Parvalbumin interneurons (PVIs) are featured with a long developmental trajectory. They are sen-sitive and susceptible to risk factors in the postnatal life. This article made a systemic review on the risk factors including dopaminergic hyperfunction, blockade of NMDA receptors, and oxidative stress. These risk factors are also involved in the pathogenesis of schizophrenia. Damaged PVIs are unable to effectively regulate their post-synaptic neurons and subsequently result in various out-comes exemplified as elevated dopamine release in cerebral cortex subsequent to the dis-inhibition on dopaminergic neurons in ventral tegmental area of the midbrain, higher levels of glutamate, which is neurotoxicity, resulting from dis-inhibition on glutamatergic neurons, and myelination deficit due to delayed development of oligodendrocyte precursor cells (OPCs) into matured oli-godendrocytes in the brain. Via the above mechanisms, PVI damage may impair the higher brain functions such as cognition, emotion, and sociability in humans thus playing a central role in the pathogenesis of schizophrenia.
| [1] | Steullet, P., Cabunqcal, J.H., Coyle, J., et al. (2017) Oxidative Stress-Driven Parvalbumin Interneuron Impairment as a Common Mechanism in Models of Schizophrenia. Molecular Psychiatry, 22, 936-943. https://doi.org/10.1038/mp.2017.47 |
| [2] | Tseng, K. and O’Donnell, P. (2007) Dopamine Modulation of Prefrontal Cortical Interneurons Changes during Adolescence. Cerebral Cortex, 17, 1235-1240. https://doi.org/10.1093/cercor/bhl034 |
| [3] | Weinberger, D.R. (1987) Implications of Normal Brain Development for the Pathogenesis of Schizophrenia. Archives of General Psychiatry, 44, 660-669. https://doi.org/10.1001/archpsyc.1987.01800190080012 |
| [4] | Schmidt, M.J. and Mimics, K. (2015) Neurodevelopment, GABA System Dysfunction, and Schizophrenia. Neuropsychopharmacology, 40, 190-206. https://doi.org/10.1038/npp.2014.95 |
| [5] | Hu, H., Gan, J. and Jonas, P. (2014) Interneurons. Fast-Spiking, Par-valbumin GABAergic Interneurons: From Cellular Design to Microcircuit Function. Science, 345, Article ID: 1255263. https://doi.org/10.1126/science.1255263 |
| [6] | Tomasella, E., Bechelli, L., Ogando, M.B., et al. (2018) Deletion of Dopamine D Receptors from Parvalbumin Interneurons in Mouse Causes Schizophrenia-Like Phenotypes. Proceedings of the National Academy of Sciences of the United States of America, 115, 3476-3481. https://doi.org/10.1073/pnas.1719897115 |
| [7] | Cardin, J.A., Carlen, M., Meletis, K., et al. (2009) Driving Fast-Spiking Cells Induces Gamma Rhythm and Controls Sensory Responses. Nature, 459, 663-667. https://doi.org/10.1038/nature08002 |
| [8] | Salinas, E. and Sejnowski, T. (2001) Correlated Neuronal Activity and the Flow of Neural Information. Nature Reviews Neuroscience, 2, 539-550. https://doi.org/10.1038/35086012 |
| [9] | Orduz, D., Maldonado, P.P., Balia, M., et al. (2015) Interneurons and Oligoden-drocyte Progenitors form a Structured Synaptic Network in the Developing Neocortex. Elife, 22, 4. https://doi.org/10.7554/eLife.06953 |
| [10] | Stedehouder, J. and Kushner, S. (2017) Myelination of Parvalbumin In-terneurons: A Parsimonious Locus of Pathophysiological Convergence in Schizophrenia. Molecular Psychiatry, 22, 4-12. https://doi.org/10.1038/mp.2016.147 |
| [11] | Carlen, M., Meletis, K., Sieqle, J.H., et al. (2012) A Critical Role for NMDA Receptors in Parvalbumin Interneurons for Gamma Rhythm Induction and Behavior. Molecular Psychiatry, 17, 537-548. https://doi.org/10.1038/mp.2011.31 |
| [12] | Tyson, J.A. and Anderson, S.A. (2014) GABAergic Interneu-ron Transplants to Study Development and Treat Disease. Trendsin Neurosciences, 37, 169-177. https://doi.org/10.1016/j.tins.2014.01.003 |
| [13] | Tricoire, L., Pelkey, K.A., Erkkila, B.E., et al. (2011) A Blueprint for the Spatiotemporal Origins of Mouse Hippocampal Interneuron Diversity. Journal of Neuroscience, 31, 10948-10970. https://doi.org/10.1523/JNEUROSCI.0323-11.2011 |
| [14] | Powell, S.B., Sejnowski, T.J. and Behrens, M.M. (2012) Behavioral and Neurochemical Consequences of Cortical Oxidative Stress on Parvalbumin-Interneuron Maturation in Rodent Models of Schizophrenia. Neuropharmacology, 62, 1322-1331. https://doi.org/10.1016/j.neuropharm.2011.01.049 |
| [15] | K？ppe, G., Bruckner, G., Hartiq, W., Delpech, B. and Bigl, V. (1997) Characterization of Proteoglycan-Containing Perineuronal Nets by Enzymatic Treatments of Rat Brain Sections. The Histochemical Journal volume, 29, 11-20. https://doi.org/10.1023/A:1026408716522 |
| [16] | H？rtiq, W., Sinqer, A., Grosche, J., et al. (2001) Perineuronal Nets in the Rat Medial Nucleus of the Trapezoid Body Surround Neurons Immunoreactive for Various Amino Acids, Calcium-Binding Proteins and the Potassium Channel Subunit Kv3.1b. Brain Research, 899, 123-133. https://doi.org/10.1016/S0006-8993(01)02211-9 |
| [17] | Wegner, F., Hartiq, W., Brinqmann, A., et al. (2003) Diffuse Perineuronal Nets and Modified Pyramidal Cells Immunoreactive for Glutamate and the GABA(A) Receptor Alpha1 Subunit form a Unique Entity in Rat Cerebral Cortex. Experimental Neurology, 184, 705-714. https://doi.org/10.1016/S0014-4886(03)00313-3 |
| [18] | Miyata, S., Nishmura, Y. and Nakashima, T. (2007) Perineuronal Nets Protect against Amyloid Beta-Protein Neurotoxicity in Cultured Cortical Neurons. Brain Re-search, 1150, 200-206. https://doi.org/10.1016/j.brainres.2007.02.066 |
| [19] | H？rtig, W., Derouiche, A., Welt, K., et al. (1999) Cortical Neurons Immunoreactive for the Potassium Channel Kv3.1b Subunit Are Predominantly Surrounded by Perineuronal Nets Presumed as a Buffering System for Cations. Brain Research, 842, 15-29. https://doi.org/10.1016/S0006-8993(99)01784-9 |
| [20] | Carulli, D., Kwok, J.C. and Pizzorusso, T. (2016) Perineu-ronal Nets and CNS Plasticity and Repair. Neural Plasticity, 2016, Article ID: 4327082. https://doi.org/10.1155/2016/4327082 |
| [21] | Carlsson, A. and Lindqvist, M. (1963) Effect of Chlorpromazine or Haloperidol on Formation of 3 Methoxytyramine and Normetanephrine in Mouse Brain. Acta Pharmacologica et Toxi-cologica, 20, 140-144. https://doi.org/10.1111/j.1600-0773.1963.tb01730.x |
| [22] | Seeman, P. and Lee, T. (1975) Antipsychotic Drugs: Direct Correlation between Clinical Potency and Presynaptic Action on Dopamine Neurons. Sci-ence, 188, 1217-1219. https://doi.org/10.1126/science.1145194 |
| [23] | Davis, K., Kahn, R.S., Ko, G., et al. (1991) Dopamine in Schizophrenia: A Review and Reconceptualization. American Journal of Psychiatry, 148, 1474-1486. https://doi.org/10.1176/ajp.148.11.1474 |
| [24] | Khan, A., de Jong, L.A., Kameski, M.E., et al. (2017) Adolescent GBR12909 Exposure Induces Oxidative Stress, Disrupts Parvalbumin-Positive Interneurons, and Leads to Hyperactivity and Impulsivity in Adult Mice. Neuroscience, 345, 166-175. https://doi.org/10.1016/j.neuroscience.2016.11.022 |
| [25] | Graham, D.L., Durai, H.H., Garden, J.D., et al. (2015) Loss of Dopamine D2 Receptors Increases Parvalbumin-Posi- tive Interneurons in the Anterior Cingulate Cortex. ACS Chemical Neuroscience, 6, 297-305. https://doi.org/10.1021/cn500235m |
| [26] | Kim, S.Y., Choi, K.C., Chanq, M.S., et al. (2006) The Dopamine D2 Receptor Regulates the Development of Dopaminergic Neurons via Extracellular Sig-nal-Regulated Kinase and Nurr1 Activation. Journal of Neuroscience, 26, 4567- 4576. https://doi.org/10.1523/JNEUROSCI.5236-05.2006 |
| [27] | Sanacora, G., Mason, G.F., Rothman, D.L., et al. (1999) Reduced Cortical Gamma-Aminobutyric Acid Levels in Depressed Patients Determined by Proton Magnetic Resonance Spectroscopy. Archives of General Psychiatry, 56, 1043- 1047. https://doi.org/10.1001/archpsyc.56.11.1043 |
| [28] | Khundakar, A., Morris, C. and Thomas, A.J. (2011) The Immuno-histochemical Examination of GABAergic Interneuron Markers in the Dorsolateral Prefrontal Cortex of Patients with Late-Life Depression. International Psychogeriatrics, 23, 644-653. https://doi.org/10.1017/S1041610210001444 |
| [29] | Bolam, J.P., Hanley, J.J., Booth, P.A. and Bevan, M.D. (2000) Synaptic Organisation of the Basal Ganglia. Journal of Anatomy, 196, 527-542. https://doi.org/10.1046/j.1469-7580.2000.19640527.x |
| [30] | Kravitz, A.V., Freeze, B.S., Parker, P.R., et al. (2010) Reg-ulation of Parkinsonian Motor Behaviours by Optogenetic Control of Basal Ganglia Circuitry. Nature, 466, 622-626. https://doi.org/10.1038/nature09159 |
| [31] | Trevitt, J.T., Morrow, J. and Marshall, J.F. (2005) Dopamine Manipula-tion Alters Immediate-Early Gene Response of Striatal Parvalbumin Interneurons to Cortical Stimulation. Brain Research, 1035, 41-50. https://doi.org/10.1016/j.brainres.2004.11.039 |
| [32] | Gittis, A.H., Hanq, G.B., LaDow, E.S., et al. (2011) Rapid Target-Specific Remodeling of Fast-Spiking Inhibitory Circuits after Loss of Dopamine. Neuron, 71, 858-868. https://doi.org/10.1016/j.neuron.2011.06.035 |
| [33] | Chu, H.Y., Ito, W., Li, J. and Morozov, A. (2012) Target-Specific Suppression of GABA Release from Parvalbumin Interneurons in the Basolateral Amygdala by Dopa-mine. Journal of Neuroscience, 32, 14815-14820. https://doi.org/10.1523/JNEUROSCI.2997-12.2012 |
| [34] | Traylenis, S.F., Wolluth, L.P., McBain, C.J., et al. (2010) Glutamate Receptor Ion Channels: Structure, Regulation, and Function. Pharmacological Reviews, 62, 405-496. https://doi.org/10.1124/pr.109.002451 |
| [35] | Hashimoto, K. (2014) Targeting of NMDA Receptors in New Treatments for Schizophrenia. Expert Opinion on Therapeutic Targets, 18, 1049-1063. https://doi.org/10.1517/14728222.2014.934225 |
| [36] | Javitt, D.C. (1987) Negative Schizophrenic Symptomatology and the PCP (Phencyclidine) Model of Schizophrenia. The Hillside Journal of Clinical Psychiatry, 9, 12-35. |
| [37] | Olney, J.W., Newcomer, J.W. and Farber, N.B. (1999) NMDA Receptor Hypofunction Model of Schizophrenia. Journal of Psychiatric Research, 33, 523-533. https://doi.org/10.1016/S0022-3956(99)00029-1 |
| [38] | Stansfield, K.H., Ruby, K.N., Soares, B.D., et al. (2015) Early-Life Lead Exposure Recapitulates the Selective Loss of Parvalbumin-Positive GABAergic Interneurons and Subcortical Dopamine System Hyperactivity Present in Schizophrenia. Translational Psy-chiatry, 5, e522. https://doi.org/10.1038/tp.2014.147 |
| [39] | Gandal, M.J., Sisti, J., Klook, K., et al. (2012) GABAB-Mediated Rescue of Altered Excitatory-Inhibitory Balance, Gamma Synchrony and Behavioral Deficits Fol-lowing Constitutive NMDAR-Hypofunction. Translational Psychiatry, 2, e142. https://doi.org/10.1038/tp.2012.69 |
| [40] | Belforte, J.E., Zsiros, V., Sklar, E.R., et al. (2010) Postnatal NMDA Re-ceptor Ablation in Corticolimbic Interneurons Confers Schizophrenia-Like Phenotypes. Nature Neuroscience, 13, 76-83. https://doi.org/10.1038/nn.2447 |
| [41] | Homayoun, H. and Moghaddam, B. (2007) NMDA Receptor Hypofunction Produces Opposite Effects on Prefrontal Cortex Interneurons and Pyramidal Neurons. Journal of Neuroscience, 27, 11496-11500. https://doi.org/10.1523/JNEUROSCI.2213-07.2007 |
| [42] | Collins, S.A., Gudelsky, G.A. and Yamamoto, B.K. (2015) MDMA-Induced Loss of Parvalbumin Interneurons within the Dentate Gyrus Is Mediated by 5HT2A and NMDA Receptors. European Journal of Pharmacology, 761, 95-100. https://doi.org/10.1016/j.ejphar.2015.04.035 |
| [43] | Emiliani, F.E., Sedlak, T.W. and Sawa, A. (2014) Oxida-tive Stress and Schizophrenia: Recent Breakthroughs from an Old Story. Current Opinion in Psychiatry, 27, 185-190. https://doi.org/10.1097/YCO.0000000000000054 |
| [44] | Radi, R. (2018) Oxygen Radicals, Nitric Oxide, and Per-oxynitrite: Redox Pathways in Molecular Medicine. Proceedings of the National Academy of Sciences of the United States of America, 115, 5839-5848. https://doi.org/10.1073/pnas.1804932115 |
| [45] | Ng, F., Berk, M., Dean, O. and Bush, A.I. (2008) Oxidative Stress in Psychiatric Disorders: Evidence Base and Therapeutic Implications. International Journal of Neuropsychopharmacology, 11, 851-876. https://doi.org/10.1017/S1461145707008401 |
| [46] | Cabungcal, J.H., Steullet, P., Kraftsik, R., Cuenod, M. and Do, K.Q. (2013) Early-Life Insults Impair Parvalbumin Interneurons via Oxi-dative Stress: Reversal by N-Acetylcysteine. Biological Psychiatry, 73, 574-482. https://doi.org/10.1016/j.biopsych.2012.09.020 |
| [47] | Walter, P.B., Knutson, M.D., Paler-Martines, A., et al. (2002) Iron Deficiency and Iron Excess Damage Mitochondria and Mitochondrial DNA in Rats. Proceedings of the National Academy of Sciences of the United States of America, 99, 2264-2269. https://doi.org/10.1073/pnas.261708798 |
| [48] | Callahan, L.S., Thibert, K.A., Wobken, J.D. and Georgieff, M.K. (2013) Early-Life Iron Deficiency Anemia Alters the Development and Long-Term Expression of Parvalbumin and Perineuronal Nets in the Rat Hippocampus. Developmental Neuroscience, 35, 427-436. https://doi.org/10.1159/000354178 |
| [49] | Radonjic, N.V., Knezevic, I.D., Vilimanovich, U., et al. (2010) Decreased Glutathione Levels and Altered Antioxidant Defense in an Animal Model of Schizophrenia: Long-Term Effects of Peri-natal Phencyclidine Administration. Neuropharmacology, 58, 739-745. https://doi.org/10.1016/j.neuropharm.2009.12.009 |
| [50] | Behrens, M.M., Ali, S.S., Dao, D.N., et al. (2007) Keta-mine-Induced Loss of Phenotype of Fast-Spiking Interneurons Is Mediated by NADPH-Oxidase. Science, 318, 1645-1647. https://doi.org/10.1126/science.1148045 |
| [51] | Lodge, D.J. and Grace, A.A. (2007) Aberrant Hippo-campal Activity Underlies the Dopamine Dysregulation in an Animal Model of Schizophrenia. Journal of Neuroscience, 27, 11424-11430. https://doi.org/10.1523/JNEUROSCI.2847-07.2007 |
| [52] | Lodge, D.J. and Grace, A.A. (2011) Hippocampal Dysregulation of Dopamine System Function and the Pathophysiology of Schizophrenia. Trends in Phar-macological Sciences, 32, 507-513. https://doi.org/10.1016/j.tips.2011.05.001 |
| [53] | Grace, A.A. and Gomes, F.V. (2019) The Circuitry of Dopamine System Regulation and Its Disruption in Schizophrenia: Insights into Treatment and Prevention. Schizophrenia Bulletin, 45, 148-157. https://doi.org/10.1093/schbul/sbx199 |
| [54] | Lodge, D.J., Behrens, M.M. and Grace, A.A. (2009) A Loss of Parvalbumin-Containing Interneurons Is Associated with Diminished Oscilla-tory Activity in an Animal Model of Schizophrenia. Journal of Neuroscience, 29, 2344-2354. https://doi.org/10.1523/JNEUROSCI.5419-08.2009 |
| [55] | Moore, H., Jentsch, J.D., Ghajarnia, M., Geyer, M.A. and Grace, A.A. (2006) A Neurobehavioral Systems Analysis of Adult Rats Exposed to Methyla-zoxymethanol Acetate on E17: Implications for the Neuropathology of Schizophrenia. Biological Psychiatry, 60, 253-264. https://doi.org/10.1016/j.biopsych.2006.01.003 |
| [56] | Boley, A.M., Perez, S.M. and Lodqe, D.J. (2014) A Funda-mental Role for Hippocampal Parvalbumin in the Dopamine Hyperfunction Associated with Schizophrenia. Schizophre-nia Research, 157, 238-243. https://doi.org/10.1016/j.schres.2014.05.005 |
| [57] | Glickstein, S.B., Moore, H., Slowinska, B., et al. (2007) Selective Cortical Interneuron and GABA Deficits in Cyclin D2-Null Mice. Development, 134, 4083-4093. https://doi.org/10.1242/dev.008524 |
| [58] | Glickstein, S.B., Monaqhan, J.A., Koeller, H.B., Jones, T.K. and Ross, M.E. (2009) Cyclin D2 Is Critical for Intermediate Progenitor Cell Proliferation in the Embryonic Cortex. Journal of Neuroscience, 29, 9614-9624. https://doi.org/10.1523/JNEUROSCI.2284-09.2009 |
| [59] | Gilani, A.I., Chohan, M.O., Inan, M., et al. (2014) Interneuron Precursor Transplants in Adult Hippocampus Reverse Psycho-sis-Relevant Features in a Mouse Model of Hippocampal Disinhibition. Proceedings of the National Academy of Sciences of the United States of America, 111, 7450-7455. https://doi.org/10.1073/pnas.1316488111 |
| [60] | Lazarus, M.S., Krishnan, K. and Huang, Z.J. (2015) GAD67 Deficiency in Parvalbumin Interneurons Produces Deficits in Inhibitory Transmission and Network Disinhibition in Mouse Prefrontal Cortex. Cerebral Cortex, 25, 1290-1296. https://doi.org/10.1093/cercor/bht322 |
| [61] | Amitai, N., Kuczenski, R., Behrens, M.M., et al. (2012) Repeated Phencyclidine Administration Alters Glutamate Release and Decreases GABA Markers in the Prefrontal Cortex of Rats. Neuropharmacology, 62, 1422-1431. https://doi.org/10.1016/j.neuropharm.2011.01.008 |
| [62] | Zhou, Z., Zhang, G., Li, X., et al. (2015) Loss of Phenotype of Parvalbumin Interneurons in Rat Prefrontal Cortex Is Involved in Antidepres-sant- and Propsychotic-Like Behaviors Following Acute and Repeated Ketamine Administration. Molecular Neurobiolo-gy, 51, 808-819. https://doi.org/10.1007/s12035-014-8798-2 |
| [63] | Emery, B. (2010) Regulation of Oligodendro-cyte Differentiation and Myelination. Science, 330, 779-782. https://doi.org/10.1126/science.1190927 |
| [64] | Boulanger, J. and Messier, C. (2017) Oligodendrocyte Progenitor Cells Are Paired with GABA Neurons in the Mouse Dorsal Cortex: Unbiased Stereological Analysis. Neu-roscience, 362, 127-140. https://doi.org/10.1016/j.neuroscience.2017.08.018 |
| [65] | Zonouzi, M., Scafidi, J., Li, P., et al. (2015) GABAergic Regulation of Cerebellar NG2 Cell Development Is Altered in Perinatal White Matter Injury. Na-ture Neuroscience, 18, 674-682. https://doi.org/10.1038/nn.3990 |
| [66] | Davis, K.L., Stewart, D.G., Friedman, J.I., et al. (2003) White Matter Changes in Schizophrenia: Evidence for Myelin-Related Dysfunction. Archives of General Psychiatry, 60, 443-456. https://doi.org/10.1001/archpsyc.60.5.443 |
| [67] | Xu, H. and Li, X.M. (2011) White Mat-ter Abnormalities and Animal Models Examining a Putative Role of Altered White Matter in Schizophrenia. Schizophre-nia Research and Treatment, 2011, Article ID: 826976. https://doi.org/10.1155/2011/826976 |
| [68] | Hakak, Y., Walker, J.R., Li, C., et al. (2001) Genome-Wide Expression Analysis Reveals Dysregulation of Myelination-Related Genes in Chronic Schizophrenia. Proceedings of the National Academy of Sciences of the United States of America, 98, 4746-4751. https://doi.org/10.1073/pnas.081071198 |
| [69] | Tishler, T.A., Bartzokis, G., Lu, P.H., et al. (2018) Ab-normal Trajectory of Intracortical Myelination in Schizophrenia Implicates Whitematter in Disease Pathophysiology and the Therapeutic Mechanism of Action of Antipsychotics. Biological Psychiatry: Cognitive Neuroscience and Neuroim-aging, 3, 454-462. https://doi.org/10.1016/j.bpsc.2017.03.007 |
| [70] | Ersland, K.M., Skrede, S., Stansberg, C. and Steen, V.M. (2017) Subchronic Olanzapine Exposure Leads to Increased Expression of Myelination-Related Genes in Rat Fronto-Medial Cortex. Translational Psychiatry, 7, 1262. https://doi.org/10.1038/s41398-017-0008-3 |
| [71] | Fang, F., Zhang, H., Zhang, Y., et al. (2013) Antipsychot-ics Promote the Differentiation of Oligodendrocyte Progenitor Cells by Regulating Oligodendrocyte Lineage Transcrip-tion Factors 1 and 2. Life Sciences, 93, 429-434. https://doi.org/10.1016/j.lfs.2013.08.004 |
| [72] | Xu, H., Yang, H.J. and Li, X.M. (2014) Differential Effects of Antipsychotics on the Development of Rat Oligodendrocyte Precursor Cells Exposed to Cuprizone. European Archives of Psychiatry and Clinical Neuroscience, 264, 121-129. https://doi.org/10.1007/s00406-013-0414-3 |
