Neuropil Alteration of the Habenula Nucleus in the Experimental Model of Schizophrenia Induced by Ketamine

Document Type : Original Article

Author

Anatomical Sciences Department, Medicine School, North Khorasan University of Medical Sciences, Bojnurd, Iran

Abstract

Background and aim: Neuropil is a densely packed network of glial processes, neuronal processes, extracellular matrix, and microvascular in the central nervous system. The habenula nucleus is one of the brain regions contributing actively to emotional processing and regulating negatively motivated behaviors. This study aimed to examine the neuropil alteration of the habenula nucleus in the experimental model of schizophrenia.
Material and methods: Twenty adult Wistar rats were randomly divided into two groups. The experimental group received ketamine at a dose of 10mg/kg intraperitoneally for one week. The control group was treated with saline. At the end of the experiment, animals were deeply anesthetized, the brains were removed, and Paraffin-embedded sections of 10µm thickness were cut on microtome. The randomized sections were stained with H&E. The position of the HB was recognized, and the neuropil surface area was measured according to the stereology method.
Results: The surface area of the right (9841±1355µm2) and the left (9110±1390.5 µm2) habenula nucleus showed a meaningful difference in comparison with the right (1134±272µm2) and the left (1247±348 µm2) habenula nucleus of the control group (p=0.000). The number of astrocytes in the right HB of the experimental group (440±96.2) and the left HB of the experimental group (422±103.2) showed a meaningful difference in comparison to those of the control group (RHB: 97±31.1 and LHB: 88±9.08) (p=0.000).
Conclusions: The results of this study showed that an experimental model of schizophrenia leads to neuropil expansion in the habenula nucleus.

Keywords

Main Subjects

References

[1] Fernandes de Lima VM, Pereira A. The plastic glial-synaptic dynamics within the neuropil: a self-organizing system composed of polyelectrolytes in phase transition. Neural Plasticity. 2016. https://doi.org/10.1155/2016/7192427.
[2] Moyle MW, Barnes KM, Kuchroo M, Gonopolskiy A, Duncan LH, Sengupta T, et al. Structural and developmental principles of neuropil assembly in C. elegans. Nature. 2021;591(7848):99-104. https://doi.org/10.1038/s41586-020-03169-5.
[3] Rash BG, Arellano JI, Duque A, Rakic P. Role of intracortical neuropil growth in the gyrification of the primate cerebral cortex. Proceedings of the National Academy of Sciences. 2023;120(1):e2210967120. https://doi.org/10.1073/pnas.2210967120.
[4] Spocter MA, Fairbanks J, Locey L, Nguyen A, Bitterman K, Dunn R, et al. Neuropil distribution in the anterior cingulate and occipital cortex of artiodactyls. The Anatomical Record. 2018;301(11):1871-81. https://doi.org/10.1002/ar.23905.
[5] Egeland J, Holmen TL, Bang-Kittilsen G, Bigseth TT, Engh JA. Category fluency in schizophrenia: opposing effects of negative and positive symptoms?. Cognitive Neuropsychiatry. 2018;23(1):28-42. https://doi.org/10.1080/13546805.2017.1418306.
[6] Prasad KM, Burgess AM, Keshavan MS, Nimgaonkar VL, Stanley JA. Neuropil pruning in early-course schizophrenia: immunological, clinical, and neurocognitive correlates. Biological Psychiatry: Cognitive Neuroscience and Neuroimaging. 2016;1(6):528-38. https://doi.org/10.1016/j.bpsc.2016.08.007.
[7] Howes OD, Cummings C, Chapman GE, Shatalina E. Neuroimaging in schizophrenia: an overview of findings and their implications for synaptic changes.   Neuropsychopharmacology.2023;48(1):151-67. https://doi.org/10.1038/s41386-022-01426-x.
[8] Hu H, Cui Y, Yang Y. Circuits and functions of the lateral habenula in health and in disease. Nature Reviews Neuroscience. 2020;21(5):277-95. https://doi.org/10.1038/s41583-020-0292-4.
[9] Johnston JN, Greenwald MS, Henter ID, Kraus C, Mkrtchian A, Clark NG, et al. Inflammation, stress and depression: an exploration of ketamine’s therapeutic profile. Drug Discovery Today. 2023;28(4):103518. https://doi.org/10.1016/j.drudis.2023.103518.
[10] Wu J, Cai Y, Wu X, Ying Y, Tai Y, He M. Transcardiac perfusion of the mouse for brain tissue dissection and fixation. Bio-protocol. 2021:e3876. https://doi.org/10.21769/BioProtoc.3876.
[11] Kikuchi T, Gonzalez-Soriano J, Kastanauskaite A, Benavides-Piccione R, Merchan-Perez A, DeFelipe J, et al. Volume electron microscopy study of the relationship between synapses and astrocytes in the developing rat somatosensory cortex. Cerebral Cortex. 2020;30(6):3800-19. https://doi.org/10.1093/cercor/bhz343.
[12] Moulson AJ, Squair JW, Franklin RJ, Tetzlaff W, Assinck P. Diversity of reactive astrogliosis in CNS pathology: heterogeneity or plasticity?. Frontiers in cellular neuroscience. 2021;15:703810. https://doi.org/10.3389/fncel.2021.703810.
[13] Dankovich TM, Rizzoli SO. The synaptic extracellular matrix: long- lived, stable, and still remarkably dynamic. Frontiers in synaptic neuroscience. 2022;14:854956. https://doi.org/10.3389/fnsyn.2022.854956.
[14] Liu F, Patterson TA, Sadovova N, Zhang X, Liu S, Zou X, et al. Ketamine-induced neuronal damage and altered N-methyl-D-aspartate receptor function in rat primary forebrain culture. toxicological sciences. 2013;131(2):548-57. https://doi.org/10.1093/toxsci/kfs296.
[15] Lisek M, Zylinska L, Boczek T. Ketamine and calcium signaling—A crosstalk for neuronal physiology and pathology. International Journal of Molecular   Sciences. 2020;21(21):8410. https://doi.org/10.3390/ijms21218410.
[16] de Bartolomeis A, Barone A, Vellucci L, Mazza B, Austin MC, Iasevoli F, et al. Linking inflammation, aberrant glutamate-dopamine interaction, and post-synaptic changes: translational relevance for schizophrenia and antipsychotic treatment: a systematic review. Molecular Neurobiology. 2022;59(10):6460-501. https://doi.org/10.1007/s12035-022-02976-3.
[17] Ahmadpour S, Behrad A, Vega IF. Dark Neurons: A protective mechanism or a mode of death. Journal of Medical Histology. 2019;3(2):125-31. https://doi.org/10.21608/jmh.2020.40221.1081.
[18] Williams JA, Burgess S, Suckling J, Lalousis PA, Batool F, Griffiths SL, et al. Inflammation and brain structure in schizophrenia and other neuropsychiatric disorders: a Mendelian randomization study. JAMA psychiatry. 2022;79(5):498-507. https://doi.org/ 10.1001/jamapsychiatry.2022.0407.
[19] Gandal MJ, Zhang P, Hadjimichael E, Walker RL, Chen C, Liu S, et al. Transcriptome-wide isoform-level dysregulation in ASD, schizophrenia, and bipolar disorder. Science. 2018;362(6420):eaat8127. https://doi.org/10.1126/science.aat8127.
[20] Chang CY, Luo DZ, Pei JC, Kuo MC, Hsieh YC, Lai WS. Not just a bystander: the emerging role of astrocytes and research tools in studying cognitive dysfunctions in schizophrenia. International journal of molecular sciences. 2021;22(10):5343. https://doi.org/10.3390/ijms22105343.
[21] Chelini G, Pantazopoulos H, Durning P, Berretta S. The tetrapartite synapse: a key concept in the pathophysiology of schizophrenia. European psychiatry. 2018;50:60-9. https://doi.org/10.1016/j.eurpsy.2018.02.003.
[22] Notter T. Astrocytes in schizophrenia. Brain and Neuroscience Advances.   2021;5:23982128211009148. https://doi.org/10.1177/23982128211009148.
[23] Van Kesteren CF, Gremmels H, De Witte LD, Hol EM, Van Gool AR, Falkai PG, et al. Immune involvement in the pathogenesis of schizophrenia: a meta-analysis on postmortem brain studies. Translational psychiatry. 2017;7(3):e1075. https://doi.org/10.1038/tp.2017.4.
[24] Foster DJ, Bryant ZK, Conn PJ. Targeting muscarinic receptors to treat schizophrenia. Behavioural brain research. 2021;405:113201. https://doi.org/10.1016/j.bbr.2021.113201.
[25] Schafer M, Kim JW, Joseph J, Xu J, Frangou S, Doucet GE. Imaging habenula volume in schizophrenia and bipolar disorder. Frontiers in psychiatry. 2018;9:456. https://doi.org/10.3389/fpsyt.2018.00456.
[26] Germann J, Gouveia FV, Martinez RC, Zanetti MV, de Souza Duran FL, Chaim-Avancini TM, et al. Fully automated habenula segmentation provides robust and reliable volume estimation across large magnetic resonance imaging datasets, suggesting intriguing developmental trajectories in psychiatric disease. Biological Psychiatry: Cognitive Neuroscience and Neuroimaging. 2020;5(9):923-9. https://doi.org/10.1016/j.bpsc.2020.01.004.
[27] Zhang L, Wang H, Luan S, Yang S, Wang Z, Wang J, et al. Altered volume and functional connectivity of the habenula in schizophrenia. Frontiers in Human Neuroscience. 2017;11:636. https://doi.org/10.3389/fnhum.2017.00636.
[28] Calì C, Wawrzyniak M, Becker C, Maco B, Cantoni M, Jorstad A, et al. The effects of aging on neuropil structure in mouse somatosensory cortex—A 3D electron microscopy analysis of layer 1. PloS one. 2018;13(7):e0198131. https://doi.org/10.1371/journal.pone.0198131.
[29] Abualait T, Alzahrani S, AlOthman A, Alhargan FA, Altwaijri N, Khallaf R, et al. Assessment of cortical plasticity in schizophrenia by transcranial magnetic stimulation. Neural Plasticity. 2021. https://doi.org/10.1155/2021/5585951.
[30] Armada-Moreira A, Gomes JI, Pina CC, Savchak OK, Gonçalves- Ribeiro J, Rei N, et al. Going the extra (synaptic) mile: excitotoxicity as the road toward neurodegenerative diseases. Frontiers in cellular neuroscience. 2020;14:90. https://doi.org/10.3389/fncel.2020.00090.
International Journal of Scientific Research in Dental and Medical Sciences
Volume 5, Issue 3 - Serial Number 3
September 2023
Pages 111-116

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History

  • Receive Date: 19 July 2023
  • Revise Date: 15 August 2023
  • Accept Date: 20 August 2023

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