Neuroserpin in Bipolar Disorder

Author(s): Rugül Köse Çinar*

Journal Name: Current Topics in Medicinal Chemistry

Volume 20 , Issue 7 , 2020

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Graphical Abstract:


Abstract:

Objective: Neuroserpin is a serine protease inhibitor predominantly expressed in the nervous system functioning mainly in neuronal migration and axonal growth. Neuroprotective effects of neuroserpin were shown in animal models of stroke, brain, and spinal cord injury. Postmortem studies confirmed the involvement of neuroserpin in Alzheimer’s disease. Since altered adult neurogenesis was postulated as an aetiological mechanism for bipolar disorder, the possible effect of neuroserpin gene expression in the disorder was evaluated.

Methods: Neuroserpin mRNA expression levels were examined in the peripheral blood of bipolar disorder type I manic and euthymic patients and healthy controls using the polymerase chain reaction method. The sample comprised of 60 physically healthy, middle-aged men as participants who had no substance use disorder.

Results: The gene expression levels of neuroserpin were found lower in the bipolar disorder patients than the healthy controls (p=0.000). The neuroserpin levels did not differ between mania and euthymia (both 96% down-regulated compared to the controls).

Conclusion: Since we detected differences between the patients and the controls, not the disease states, the dysregulation in the neuroserpin gene could be interpreted as a result of the disease itself.

Keywords: Bipolar disorder, Peripheral blood, mRNA expression, Neuroserpin, Neurogenesis, Neuroprotection.

[1]
Vieta, E.; Berk, M.; Schulze, T.G.; Carvalho, A.F.; Suppes, T.; Calabrese, J.R.; Gao, K.; Miskowiak, K.W.; Grande, I. Bipolar disorders. Nat. Rev. Dis. Primers, 2018, 4, 18008.
[http://dx.doi.org/10.1038/nrdp.2018.8] [PMID: 29516993]
[2]
Binbay, T.A.K.; Elbi, H.; Zağlı, N.; Drukker, M.; Tanık, F.A. Lifetime prevalence and correlates of schizophrenia and disorders with psychotic symptoms in the general population of Izmir, Turkey. Turk Psikiyatr. Derg., 2012, 23, 149-160.
[3]
Eaton, W.W. C. C.; Bromet, EJ. Epidemiology of Schizophrenia. In: Textbook of Psychiatric Epidemiology; Tsuang, M.T.; Tohen, M.; Jones, P., Eds.; John Wiley and Sons: Hoboken, 2011; pp. 263-263.
[4]
Vawter, M.P.; Shannon Weickert, C.; Ferran, E.; Matsumoto, M.; Overman, K.; Hyde, T.M.; Weinberger, D.R.; Bunney, W.E.; Kleinman, J.E. Gene expression of metabolic enzymes and a protease inhibitor in the prefrontal cortex are decreased in schizophrenia. Neurochem. Res., 2004, 29(6), 1245-1255.
[http://dx.doi.org/10.1023/B:NERE.0000023611.99452.47] [PMID: 15176481]
[5]
Galliciotti, G.; Sonderegger, P. Neuroserpin. Front. Biosci., 2006, 11, 33-45.
[http://dx.doi.org/10.2741/1778] [PMID: 16146712]
[6]
Lee, T.W.; Tsang, V.W.; Birch, N.P. Physiological and pathological roles of tissue plasminogen activator and its inhibitor neuroserpin in the nervous system. Front. Cell. Neurosci., 2015, 9, 396.
[http://dx.doi.org/10.3389/fncel.2015.00396] [PMID: 26528129]
[7]
Wu, J.; Echeverry, R.; Guzman, J.; Yepes, M. Neuroserpin protects neurons from ischemia-induced plasmin-mediated cell death independently of tissue-type plasminogen activator inhibition. Am. J. Pathol., 2010, 177(5), 2576-2584.
[http://dx.doi.org/10.2353/ajpath.2010.100466] [PMID: 20864675]
[8]
Yepes, M.; Lawrence, D.A. Tissue-type plasminogen activator and neuroserpin: a well-balanced act in the nervous system? Trends Cardiovasc. Med., 2004, 14(5), 173-180.
[http://dx.doi.org/10.1016/j.tcm.2004.03.004] [PMID: 15261888]
[9]
Wang, L.; Zhang, Y.; Asakawa, T.; Li, W.; Han, S.; Li, Q.; Xiao, B.; Namba, H.; Lu, C.; Dong, Q. Neuroprotective effect of neuroserpin in oxygen-glucose deprivation- and reoxygenation-treated rat astrocytes in vitro. PLoS One, 2015, 10(4)e0123932
[http://dx.doi.org/10.1371/journal.pone.0123932] [PMID: 25874935]
[10]
Roussel, B.D.; Lomas, D.A.; Crowther, D.C. Progressive myoclonus epilepsy associated with neuroserpin inclusion bodies (neuroserpinosis). Epileptic Disord., 2016, 18(S2), 103-110.
[http://dx.doi.org/10.1684/epd.2016.0847] [PMID: 27618835]
[11]
Ma, J.; Tong, Y.; Yu, D.; Mao, M. Tissue plasminogen activator-independent roles of neuroserpin in the central nervous system. Neural Regen. Res., 2012, 7(2), 146-151.
[PMID: 25767491]
[12]
Fabbro, S.; Seeds, N.W. Plasminogen activator activity is inhibited while neuroserpin is up-regulated in the Alzheimer disease brain. J. Neurochem., 2009, 109(2), 303-315.
[http://dx.doi.org/10.1111/j.1471-4159.2009.05894.x] [PMID: 19222708]
[13]
Kinghorn, K.J.; Crowther, D.C.; Sharp, L.K.; Nerelius, C.; Davis, R.L.; Chang, H.T.; Green, C.; Gubb, D.C.; Johansson, J.; Lomas, D.A. Neuroserpin binds Abeta and is a neuroprotective component of amyloid plaques in Alzheimer disease. J. Biol. Chem., 2006, 281(39), 29268-29277.
[http://dx.doi.org/10.1074/jbc.M600690200] [PMID: 16849336]
[14]
Brennand, K.J.; Simone, A.; Jou, J.; Gelboin-Burkhart, C.; Tran, N.; Sangar, S.; Li, Y.; Mu, Y.; Chen, G.; Yu, D.; McCarthy, S.; Sebat, J.; Gage, F.H. Modelling schizophrenia using human induced pluripotent stem cells. Nature, 2011, 473(7346), 221-225.
[http://dx.doi.org/10.1038/nature09915] [PMID: 21490598]
[15]
Hakak, Y.; Walker, J.R.; Li, C.; Wong, W.H.; Davis, K.L.; Buxbaum, J.D.; Haroutunian, V.; Fienberg, A.A. Genome-wide expression analysis reveals dysregulation of myelination-related genes in chronic schizophrenia. Proc. Natl. Acad. Sci. USA, 2001, 98(8), 4746-4751.
[http://dx.doi.org/10.1073/pnas.081071198] [PMID: 11296301]
[16]
Wen, Z.; Nguyen, H.N.; Guo, Z.; Lalli, M.A.; Wang, X.; Su, Y.; Kim, N.S.; Yoon, K.J.; Shin, J.; Zhang, C.; Makri, G.; Nauen, D.; Yu, H.; Guzman, E.; Chiang, C.H.; Yoritomo, N.; Kaibuchi, K.; Zou, J.; Christian, K.M.; Cheng, L.; Ross, C.A.; Margolis, R.L.; Chen, G.; Kosik, K.S.; Song, H.; Ming, G.L. Synaptic dysregulation in a human iPS cell model of mental disorders. Nature, 2014, 515(7527), 414-418.
[http://dx.doi.org/10.1038/nature13716] [PMID: 25132547]
[17]
Reumann, R.; Vierk, R.; Zhou, L.; Gries, F.; Kraus, V.; Mienert, J.; Romswinkel, E.; Morellini, F.; Ferrer, I.; Nicolini, C.; Fahnestock, M.; Rune, G.; Glatzel, M.; Galliciotti, G. The serine protease inhibitor neuroserpin is required for normal synaptic plasticity and regulates learning and social behavior. Learn. Mem., 2017, 24(12), 650-659.
[http://dx.doi.org/10.1101/lm.045864.117] [PMID: 29142062]
[18]
Merikangas, K.R.; Jin, R.; He, J.P.; Kessler, R.C.; Lee, S.; Sampson, N.A.; Viana, M.C.; Andrade, L.H.; Hu, C.; Karam, E.G.; Ladea, M.; Medina-Mora, M.E.; Ono, Y.; Posada-Villa, J.; Sagar, R.; Wells, J.E.; Zarkov, Z. Prevalence and correlates of bipolar spectrum disorder in the world mental health survey initiative. Arch. Gen. Psychiatry, 2011, 68(3), 241-251.
[http://dx.doi.org/10.1001/archgenpsychiatry.2011.12] [PMID: 21383262]
[19]
Köse Çinar, R.; Sönmez, M.B.; Görgülü, Y. Peripheral blood mRNA expressions of stress biomarkers in manic episode and subsequent remission. Psychoneuroendocrinology, 2016, 70, 10-16.
[http://dx.doi.org/10.1016/j.psyneuen.2016.04.020] [PMID: 27138695]
[20]
Livak, K.J.; Schmittgen, T.D. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods, 2001, 25(4), 402-408.
[http://dx.doi.org/10.1006/meth.2001.1262] [PMID: 11846609]
[21]
Pang, P.T.; Teng, H.K.; Zaitsev, E.; Woo, N.T.; Sakata, K.; Zhen, S.; Teng, K.K.; Yung, W.H.; Hempstead, B.L.; Lu, B. Cleavage of proBDNF by tPA/plasmin is essential for long-term hippocampal plasticity. Science, 2004, 306(5695), 487-491.
[http://dx.doi.org/10.1126/science.1100135] [PMID: 15486301]
[22]
Buoli, M.; Serati, M.; Caldiroli, A.; Cremaschi, L.; Altamura, A.C. Neurodevelopmental versus neurodegenerative model of schizophrenia and bipolar disorder: comparison with physiological brain development and aging. Psychiatr. Danub., 2017, 29(1), 24-27.
[http://dx.doi.org/10.24869/psyd.2017.24] [PMID: 28291970]
[23]
Lee, T.W.; Tsang, V.W.; Loef, E.J.; Birch, N.P. Physiological and pathological functions of neuroserpin: Regulation of cellular responses through multiple mechanisms. Semin. Cell Dev. Biol., 2017, 62, 152-159.
[http://dx.doi.org/10.1016/j.semcdb.2016.09.007] [PMID: 27639894]
[24]
Chéret, J.; Lebonvallet, N.; Misery, L.; Le Gall-Ianotto, C. Expression of neuroserpin, a selective inhibitor of tissue-type plasminogen activator in the human skin. Exp. Dermatol., 2012, 21(9), 710-711.
[http://dx.doi.org/10.1111/j.1600-0625.2012.01541.x] [PMID: 22742704]
[25]
Rodríguez-González, R.; Millán, M.; Sobrino, T.; Miranda, E.; Brea, D.; de la Ossa, N.P.; Blanco, M.; Perez, J.; Dorado, L.; Castellanos, M.; Lomas, D.A.; Moro, M.A.; Dávalos, A.; Castillo, J. The natural tissue plasminogen activator inhibitor neuroserpin and acute ischaemic stroke outcome. Thromb. Haemost., 2011, 105(3), 421-429.
[http://dx.doi.org/10.1160/TH10-09-0621] [PMID: 21174006]
[26]
Ghavami, S.; Shojaei, S.; Yeganeh, B.; Ande, S.R.; Jangamreddy, J.R.; Mehrpour, M.; Christoffersson, J.; Chaabane, W.; Moghadam, A.R.; Kashani, H.H.; Hashemi, M.; Owji, A.A.; Łos, M.J. Autophagy and apoptosis dysfunction in neurodegenerative disorders. Prog. Neurobiol., 2014, 112, 24-49.
[http://dx.doi.org/10.1016/j.pneurobio.2013.10.004] [PMID: 24211851]
[27]
Li, W.; Asakawa, T.; Han, S.; Xiao, B.; Namba, H.; Lu, C.; Dong, Q.; Wang, L. Neuroprotective effect of neuroserpin in non-tPA-induced intracerebral hemorrhage mouse models. BMC Neurol., 2017, 17(1), 196.
[http://dx.doi.org/10.1186/s12883-017-0976-1] [PMID: 29115923]
[28]
Wu, W.; Asakawa, T.; Yang, Q.; Zhao, J.; Lu, L.; Luo, Y.; Gong, P.; Han, S.; Li, W.; Namba, H.; Wang, L. Effects of neuroserpin on clinical outcomes and inflammatory markers in Chinese patients with acute ischemic stroke. Neurol. Res., 2017, 39(10), 862-868.
[http://dx.doi.org/10.1080/01616412.2017.1357780] [PMID: 28738762]
[29]
Fries, G.R.; Vasconcelos-Moreno, M.P.; Gubert, C.; Santos, B.T.; da Rosa, A.L.; Eisele, B.; Sartori, J.; Pfaffenseller, B.; Kapczinski, F.; Kauer-Sant’anna, M. Early apoptosis in peripheral blood mononuclear cells from patients with bipolar disorder. J. Affect. Disord., 2014, 152-154, 474-477.
[http://dx.doi.org/10.1016/j.jad.2013.07.027] [PMID: 24007785]
[30]
Higashi, M.; Maruta, N.; Bernstein, A.; Ikenaka, K.; Hitoshi, S. Mood stabilizing drugs expand the neural stem cell pool in the adult brain through activation of notch signaling. Stem Cells, 2008, 26(7), 1758-1767.
[http://dx.doi.org/10.1634/stemcells.2007-1032] [PMID: 18467661]
[31]
Hayashi, Y.; Jinnou, H.; Sawamoto, K.; Hitoshi, S. Adult neurogenesis and its role in brain injury and psychiatric diseases. J. Neurochem., 2018, 147(5), 584-594.
[http://dx.doi.org/10.1111/jnc.14557] [PMID: 30028510]
[32]
Raedler, T.J.; Knable, M.B.; Weinberger, D.R. Schizophrenia as a developmental disorder of the cerebral cortex. Curr. Opin. Neurobiol., 1998, 8(1), 157-161.
[http://dx.doi.org/10.1016/S0959-4388(98)80019-6] [PMID: 9568403]
[33]
Vawter, M.P.; Barrett, T.; Cheadle, C.; Sokolov, B.P.; Wood, W.H., III; Donovan, D.M.; Webster, M.; Freed, W.J.; Becker, K.G. Application of cDNA microarrays to examine gene expression differences in schizophrenia. Brain Res. Bull., 2001, 55(5), 641-650.
[http://dx.doi.org/10.1016/S0361-9230(01)00522-6] [PMID: 11576761]
[34]
Ogłodek, E.A.; Just, M.J.; Grzesińska, A.D.; Araszkiewicz, A.; Szromek, A.R. The impact of antipsychotics as a risk factor for thromboembolism. Pharmacol. Rep., 2018, 70(3), 533-539.
[http://dx.doi.org/10.1016/j.pharep.2017.12.003] [PMID: 29674240]
[35]
Pisanu, C.; Katsila, T.; Patrinos, G.P.; Squassina, A. Recent trends on the role of epigenomics, metabolomics and noncoding RNAs in rationalizing mood stabilizing treatment. Pharmacogenomics, 2018, 19(2), 129-143.
[http://dx.doi.org/10.2217/pgs-2017-0111] [PMID: 29199496]
[36]
Balasubramanian, D.; Pearson, J.F.; Kennedy, M.A. Gene expression effects of lithium and valproic acid in a serotonergic cell line. Physiol. Genomics, 2018, 51(2), 43-50.
[http://dx.doi.org/10.1152/physiolgenomics.00069.2018] [PMID: 30576260]


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Article Details

VOLUME: 20
ISSUE: 7
Year: 2020
Page: [518 - 523]
Pages: 6
DOI: 10.2174/1568026620666200131125526
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