The effects of blood serum from schizophrenia patients under olanzapine monotherapy on the ultrastructure of astrocytes in human fetal brain organotypic culture

Kolomeets N.S.; Vostrikov V.M.; Uranova N.A.

doi:https://doi.org/10.17116/jnevro20161165165-70

Kolomeets N.S.

Nauchnyĭ tsentr psikhicheskogo zdorov'ia RAMN, Moskva

Vostrikov V.M.

FGBU "Nauchnyĭ tsentr psikhicheskogo zdorov'ia" RAMN, Moskva

Uranova N.A.

Nauchnyĭ tsentr psikhicheskogo zdorov'ia RAMN, Moskva

The effects of blood serum from schizophrenia patients under olanzapine monotherapy on the ultrastructure of astrocytes in human fetal brain organotypic culture

Authors:

Kolomeets N.S., Vostrikov V.M., Uranova N.A.

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Journal: S.S. Korsakov Journal of Neurology and Psychiatry. 2016;116(5): 65‑70

DOI: 10.17116/jnevro20161165165-70

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Kolomeets NS, Vostrikov VM, Uranova NA. The effects of blood serum from schizophrenia patients under olanzapine monotherapy on the ultrastructure of astrocytes in human fetal brain organotypic culture. S.S. Korsakov Journal of Neurology and Psychiatry. 2016;116(5):65‑70. (In Russ.)
https://doi.org/10.17116/jnevro20161165165-70

Подписка 2026 Журнал неврологии и психиатрии им. С.С. Корсакова (S.S. Korsakov Journal of Neurology and Psychiatry)

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Abstract:

Objective. To study effects of blood serum (BS) from schizophrenia patients under olanzapine monotherapy on astrocytes in the human fetal brain organotypic culture. Material and methods. Authors studied the human fetal brain organotypic culture after the application of BS from 20 normals and 33 patients (ICD-10 schizophrenia, paranoid type, F20.02; F20.22) taken before and after 8 and 28 weeks of olanzapine treatment. A qualitative electron microscopic study of glial cells, neurons and neuropil as well as morphometric study of the ultrastructure of astrocytes were performed. Results. Authors found no effects of BS from the patients with schizophrenia on neurons and synaptic contacts. The qualitative and morphometric studies revealed different effects of BS from the patients on the astrocyte ultrastructure before and after olanzapine treatment. The application of BS from untreated schizophrenia patients induced dystrophic alterations of astrocytes, BS from patients who received olanzapine during 8 weeks did not influence the astrocyte ultrastructure. After 28 weeks of olanzapine treatment,a hypertrophy of astrocytes (an increase (р≤0.05) of the area of cells and the number of mitochondria (p=0,015) and unaltered volume density of mitochondria) was found as compared to normal control cultures. Conclusion. BS from patients with schizophrenia before and after olanzapine treatment induced opposite types of ultrastructural changes of astrocytes in the human fetal brain organotypic culture. The differences might be due to the previously reported changes of the level of circulating immune complexes and interleukins in blood serum of schizophrenia patients and due to the effects of olanzapine on these parameters.

Keywords:

schizophrenia

blood serum

olanzapine

astrocytes

ultrastructure

human fetal brain organotypic culture

Authors:

Kolomeets N.S.

Nauchnyĭ tsentr psikhicheskogo zdorov'ia RAMN, Moskva

Vostrikov V.M.

FGBU "Nauchnyĭ tsentr psikhicheskogo zdorov'ia" RAMN, Moskva

Uranova N.A.

Nauchnyĭ tsentr psikhicheskogo zdorov'ia RAMN, Moskva

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References:

Kolomeec NS, Vostrikov VM, Uranova NA. Vlijanie syvorotki krovi ot bol'nyh shizofreniej na astrocity v kul'ture tkani jembrional'nogo mozga cheloveka: morfometricheskoe issledovanie. Zhurnal nevrologii i psihiatrii im. S.S. Korsakova. 2015;115(6):71-77. (In Russ.).
Koljaskina GI, Sekirina TP, Androsova LV, Kushner SG, Vasil'eva EF, Burbaeva OA, Morozova MA. Izmenenie immunnogo profilja bol'nyh shizofreniej v processe lechenija. Zhurnal nevrologii i psihiatrii im. S.S. Korsakova. 2004;104(4):39-45. (In Russ.).
Borda T, Gomez R, Berria MI, Sterin-Borda L. Antibodies against astrocyte M1 and M2 muscarinic cholinoceptor from schizophrenic patients' sera. Glia. 2004; 45(2):144-154. doi: 10.1002/glia.10312.
Jones AL, Mowry BJ, McLean DE, Mantzioris BX, Pender MP, Greer JM. Elevated levels of autoantibodies targeting the M1 muscarinic acetylcholine receptor and neurofilament medium in sera from subgroups of patients with schizophrenia. J Neuroimmunol. 2014;269(1-2):68-75. doi: 10.1016/j.jneuroim. 2014.02.008.
Pollak TA, McCormack R, Peakman M, Nicholson TR, David AS. Prevalence of anti-N-methyl-D-aspartate (NMDA) receptor antibodies in patients with schizophrenia and related psychoses: a systematic review and meta-analysis. Psychol Med. 2014;44(12):2475-2487. doi: 10.1017/ S003329171300295X.
Steiner J, Walter M, Glanz W, Sarnyai Z, Bernstein HG, Vielhaber S, Kästner A, Skalej M, Jordan W, Schiltz K, Klingbeil C, Wandinger KP, Bogerts B, Stoecker W. Increased prevalence of diverse N-methyl-D-aspartate glutamate receptor antibodies in patients with an initial diagnosis of schizophrenia: specific relevance of IgG NR1a antibodies for distinction from N-methyl-D-aspartate glutamate receptor encephalitis. JAMA Psychiatry. 2013;70(3):271-278. doi: 10.1001/2013.jamapsychiatry.86.
Bsibsi M, Persoon-Deen C, Verwer RW, Meeuwsen S, Ravid R, Van Noort JM. Toll-like receptor 3 on adult human astrocytes triggers production of neuroprotective mediators. Glia. 2006;53:688-695. doi: 10.1002/glia.20328.
Hailer NP, Wirjatijasa F, Roser N, Hischebeth GT, Korf HW, Dehghani F. Astrocytic factors protect neuronal integrity and reduce microglial activation in an in vitro model of N-methyl-D-aspartate-induced excitotoxic injury in organotypic hippocampal slice cultures. Eur J Neurosci. 2001;14:315-326. doi: 10.1046/j.0953-816x.2001.01649.x.
Drzyzga L, Obuchowicz E, Marcinowska A, Herman ZS. Cytokines in schizophrenia and the effects of antipsychotic drugs. Brain Behav Immun. 2006;20(6):532-545. doi: 10.1016/j.bbi. 2006.02.002.
Schuld A, Kraus T, Haack M, Hinze-Selch D, Kühn M, Pollmächer T. Plasma levels of cytokines and soluble cytokine receptors during treatment with olanzapine. Schizophr Res. 2000;43(2-3):164-166.
Sugino H, Futamura T, Mitsumoto Y, Maeda K, Marunaka Y. Atypical antipsychotics suppress production of proinflammatory cytokines and up-regulate interleukin-10 in lipopolysaccharide-treated mice. Prog Neuropsychopharmacol Biol Psychiatry. 2009;33(2):303-307. doi: 10.1016/ j.pnpbp. 2008.12.006.
Szuster-Ciesielska A, Słotwińska M, Stachura A, Marmurowska-Michałowska H, Kandefer-Szerszeń M. Neuroleptics modulate cytokine and reactive oxygen species production in blood leukocytes of healthy volunteers. Arch Immunol Ther Exp (Warsz). 2004;52(1):59-67.
Bhana N, Foster RH, Olney R, Plosker GL. Olanzapine: an updated review of its use in the management of schizophrenia. Drugs. 2001;61(1):111-161. doi: 10.2165/00003495-200161010-00011.
Brusov OS, Faktor MI, Zlobina GP, Dupin AM, Katasonov AB, Karceva NK, Beniashvili AG, Zharkova NB, Rubashkina VV, Morozova MA. Serotoninovaja sistema trombocitov u bol'nyh shizofreniej pri lechenii olanzapinom: poisk serotoninergicheskih prediktorov terapevticheskoj jeffektivnosti. Zhurnal nevrologii i psihiatrii im. S.S. Korsakova. 2005;105(3):27-34. (In Russ.).
Burbaeva GSh, Boksha IS, Starodubceva LI, Savushkina OK, Tereshkina EB, Turishheva MS, Prohorova TA, Vorob'eva EA, Morozova MA. Narushenie metabolizma glutamata pri shizofrenii. Vestnik RAMN. 2007;3:19-24. (In Russ.).
Vostrikov VM, Kolomeec NS, Aleksandrova OP, Viktorov IV, Uranova NA, Suhih GT. Organotipicheskaja kul'tura svobodno-plavajushhih srezov prodolgovatogo mozga jembriona cheloveka. Morfologija. 2003;124(4):41-47.
Kim JH, Song AR, Sohn HJ, Lee J, Yoo JK, Kwon D, Shin HJ. IL-1β and IL-6 activate inflammatory responses of astrocytes against Naegleria fowleri infection via the modulation of MAPKs and AP-1. Parasite Immunol. 2013;35(3-4):120-128. doi: 10.1111/pim.12021.
Selmaj KW, Farooq M, Norton WT, Raine CS, Brosnan CF. Proliferation of astrocytes in vitro in response to cytokines. A primary role for tumor necrosis factor. J Immunol. 1990;144(1):129-135.
Woiciechowsky C, Schoning B, Stoltenburg-Didinger G, Stockhammer F, Volk HD. Brain-IL-1 beta triggers astrogliosis through induction of IL-6: inhibition by propranolol and IL-10. Med Sci Monit. 2004;10(9):325-330.
Friede RL. Developmental neuropathology. Berlin: Springer Verlag; 1989.
Söderlund J, Schröder J, Nordin C, Samuelsson M, Walther-Jallow L, Karlsson H, Erhardt S, Engberg G. Activation of brain interleukin-1β in schizophrenia. Mol Psychiatry. 2009;14(12):1069-1071. doi: 10.1038/mp.2009.52.
Papiol S, Rosa A, Gutiérrez B, Martín B, Salgado P, Catalán R, Arias B, Fananas L. Interleukin-1 cluster is associated with genetic risk for schizophrenia and bipolar disorder. J Med Genet. 2004;41(3):219-223. doi: 10.1136/jmg.2003.012914.
Hänninen K, Katila H, Saarela M, Rontu R, Mattila KM, Fan M, Hurme M, Lehtimäki T. Interleukin-1 beta gene polymorphism and its interactions with neuregulin-1 gene polymorphism are associated with schizophrenia. Eur Arch Psychiatry Clin Neurosci. 2008;258(1):10-15. doi: 10.1007/ s00406-007-0756-9.
Moynagh PN. The interleukin-1 signalling pathway in astrocytes: a key contributor to inflammation in the brain. J Anat. 2005;207(3):265-269. doi: 10.1111/j.1469-7580.2005.00445.x
Lee SC, Dickson DW, Brosnan CF. Interleukin-1, nitric oxide and reactive astrocytes. Brain Behav Immunol. 1995;9(4):345-354. doi:10.1006/brbi.1995.1032.
Balasingam V, Yong VW. Attenuation of astroglial reactivity by interleukin-10. J Neurosci. 1996;16(9):2945-2955.
Quincozes-Santos A, Abib RT, Leite MC, Bobermin D, Bambini-Junior V, Gonçalves CA, Riesgo R, Gottfried C. Effect of the atypical neuroleptic risperidone on morphology and S100B secretion in C6 astroglial lineage cells. Mol Cell Biochem. 2008;314(1-2):59-63. doi: 10.1007/s11010-008-9765-x.
Quincozes-Santos A, Bobermin LD, Tonial RP, Bambini-Junior V, Riesgo R, Gottfried C. Effects of atypical (risperidone) and typical (haloperidol) antipsychotic agents on astroglial functions. Eur Arch Psychiatry Clin Neurosci. 2010;260(6):475-481. doi: 10.1007/s00406-009-0095-0.