Effect on the expression of drd2 and drd3 after neonatal lesion in the lymphocytes, nucleus accumbens, hippocampus and prefrontal cortex: comparative analysis between juvenile and adult Wistar rats
Tóm tắt
Neonatal lesion in the ventral hippocampus (NLVH) is a validated animal model to study schizophrenia from a neurodevelopmental perspective. This animal model is also used to investigate how neonatal lesions may alter the genetic expression of dopaminergic receptors. The present study compares mRNA expression levels of dopamine receptors (drd2 and drd3) in lymphocytes and brain of NLVH animals at two different age stages: young and adult. The NLVH procedure was performed on 20 male Wistar rats at postnatal days 5–7. The mRNA expression levels of drd2 and drd3 genes in lymphocytes, nucleus accumbens, hippocampus and prefrontal cortex were measured and analyzed at postnatal days 45 and 90. The results were compared and contrasted with respective sham groups. In lymphocytes, only in NLVH-adult group we observed drd2 mRNA expression, while drd2 mRNA expression was not observed in the NLVH-juvenile rats; on the other hand, the drd3 mRNA expression did not show significant statistical differences. In hippocampus no differences were observed between drd2 mRNA or drd3 mRNA expression when comparing juvenile/adult shams with NLVH groups. In the prefrontal area, a decrease in drd2 mRNA expression levels were observed in the NLVH-adult group (F(1,3) = 52.83, p = 0,005) in comparison to the sham-adult group. Finally, in the nucleus accumbens, a strong decrease of drd3 mRNA expression was observed in the NLVH-adult group in comparison to the sham-adult group (F(1,3) = 123,2, p < 0.001). Our results show that differences in drd2 and drd3 mRNA levels in NLVH-adults are patent when compared to the sham-adult group or with the NLVH-juvenile group. These findings suggest that the expression levels may be regulated during adulthood, leading to behavioral and neurochemical changes related to schizophrenia. Therefore, more studies are necessary to determine the role of dopamine receptors as possible molecular markers for neurodevelopmental changes associated with schizophrenia.
Tài liệu tham khảo
McGrath J, Saha S, Chant D, Welham J. Schizophrenia: A concise overview of incidence, prevalence, and mortality. Epidemiol Rev. 2008;30:67–76.
Vereczkei A, Mirnics K. Genetic predisposition to schizophrenia: What did we learn and what does the future hold? Neuropsychopharmacol Hung. 2011;13:205–10.
Lovic V, Belay H, Walker CD, Burton CL, Meaney MJ, Sokolowski M, Fleming AS. Early postnatal experience and drd2 genotype affect dopamine receptor expression in the rat ventral striatum. Behav Brain Res. 2013;237:278–82.
Dolzan V, Plesnicar BK, Serretti A, Mandelli L, Zalar B, Koprivsek J, Breskvar K. Polymorphisms in dopamine receptor drd1 and drd2 genes and psychopathological and extrapyramidal symptoms in patients on long-term antipsychotic treatment. Am J Med Genet B Neuropsychiatr Genet. 2007;5:809–15.
Genis-Mendoza AD, Gallegos-Silva RI, Lopez-Casamichana M, Lopez-Rubalcava C, Nicolini H. Gene expression profiles of nucleus accumbens, prefrontal cortex and hippocampus in an animal model of schizophrenia: Proposed candidate genes. Actas Esp Psiquiatr. 2013;41:154–63.
Lillrank SM, Lipska BK, Weinberger DR. Neurodevelopmental animal models of schizophrenia. Clin Neurosci. 1995;3:98–104.
Chen XS, Zhang C, Xu YF, Zhang MD, Lou FY, Chen C, Tang J. Neonatal ventral hippocampal lesion as a valid model of schizophrenia: Evidence from sensory gating study. Chin Med J. 2012;125:2752–4.
Valdes-Cruz A, Negrete-Diaz JV, Magdaleno-Madrigal VM, Martinez-Vargas D, Fernandez-Mas R, Almazan-Alvarado S, Torres-Garcia ME, Flores G. Electroencephalographic activity in neonatal ventral hippocampus lesion in adult rats. Synapse. 2012;66:738–46.
Tseng KY, Chambers RA, Lipska BK. The neonatal ventral hippocampal lesion as a heuristic neurodevelopmental model of schizophrenia. Behav Brain Res. 2009;204:295–305.
Lambe EK, Krimer LS, Goldman-Rakic PS. Differential postnatal development of catecholamine and serotonin inputs to identified neurons in prefrontal cortex of rhesus monkey. J Neurosci. 2000;20:8780–7.
Tucker DM, Derryberry D, Luu P. Anatomy and physiology of human emotion: Vertical integration of brainstem, limbic, and cortical systems. Oxford: New York; 2000.
Padin JF, Rodriguez MA, Dominguez E, Dopeso-Reyes IG, Buceta M, Cano E, Sotelo E, Brea J, Caruncho HJ, Isabel Cadavid M, et al. Parallel regulation by olanzapine of the patterns of expression of 5-ht2a and d3 receptors in rat central nervous system and blood cells. Neuropharmacology. 2006;51:923–32.
Lisak RP, Benjamins JA, Bealmear B, Nedelkoska L, Studzinski D, Retland E, Yao B, Land S. Differential effects of th1, monocyte/macrophage and th2 cytokine mixtures on early gene expression for molecules associated with metabolism, signaling and regulation in central nervous system mixed glial cell cultures. J Neuroinflammation. 2009;6:1742–2094.
Lambert G, Johansson M, Agren H, Friberg P. Reduced brain norepinephrine and dopamine release in treatment-refractory depressive illness: Evidence in support of the catecholamine hypothesis of mood disorders. Arch Gen Psychiatry. 2000;57:787–93.
Domenici E, Wille DR, Tozzi F, Prokopenko I, Miller S, McKeown A, Brittain C, Rujescu D, Giegling I, Turck CW, et al. Plasma protein biomarkers for depression and schizophrenia by multi analyte profiling of case-control collections. PLoS One. 2010;5:0009166.
Caronti B, Calderaro C, Passarelli F, Palladini G, Pontieri FE. Dopamine receptor mrnas in the rat lymphocytes. Life Sci. 1998;62:1919–25.
Saurer TB, Ijames SG, Lysle DT. Evidence for the nucleus accumbens as a neural substrate of heroin-induced immune alterations. J Pharmacol Exp Ther. 2009;329:1040–7.
Genis-Mendoza AD, Beltran-Villalobos I, Nicolini-Sanchez H. behavioral assessment of the “schizophrenia-like” phenotype in an animal model of neonatal lesion in the ventral hippocampus (nlvh) of young and adult rats. Gac Med Mex. 2014;150:420–31.
Zimmermann M. Ethical principles for the maintenance and use of animals in neuroscience research. Neurosci Lett. 1987;73(1):1.
Lipska BK. Using animal models to test a neurodevelopmental hypothesis of schizophrenia. J Psychiatry Neurosci. 2004;29(4):282–286.
Lipska BK, Jaskiw GE, Chrapusta S, Karoum F, Weinberger DR. Ibotenic acid lesion of the ventral hippocampus differentially affects dopamine and its metabolites in the nucleus accumbens and prefrontal cortex in the rat. Brain Res. 1992;585:1–6.
Teicher MH, Andersen SL, Polcari A, Anderson CM, Navalta CP. Developmental neurobiology of childhood stress and trauma. Psychiatr Clin North Am. 2002;25:397–426. vii-viii.
Rakic P. Radial unit hypothesis of neocortical expansion. Novartis Found Symp. 2000;228:30–42. discussion 42–52.
Flores G, Wood GK, Liang JJ, Quirion R, Srivastava LK. Enhanced amphetamine sensitivity and increased expression of dopamine d2 receptors in postpubertal rats after neonatal excitotoxic lesions of the medial prefrontal cortex. J Neurosci. 1996;16:7366–75.
El-Rawas R, Saade NE, Thiriet N, Atweh S, Jaber M, Al-Amin HA. Developmental changes in the mrna expression of neuropeptides and dopamine and glutamate receptors in neonates and adult rats after ventral hippocampal lesion. Schizophr Res. 2009;113:298–307.
Lipska BK, Lerman DN, Khaing ZZ, Weinberger DR. The neonatal ventral hippocampal lesion model of schizophrenia: Effects on dopamine and gaba mrna markers in the rat midbrain. Eur J Neurosci. 2003;18:3097–104.
Durstewitz D, Seamans JK, Sejnowski TJ. Dopamine-mediated stabilization of delay-period activity in a network model of prefrontal cortex. J Neurophysiol. 2000;83:1733–50.
Takahashi H. Pet neuroimaging of extrastriatal dopamine receptors and prefrontal cortex functions. J Physiol Paris. 2013;107:503–9.
Selemon LD, Zecevic N. Schizophrenia: A tale of two critical periods for prefrontal cortical development. Transl Psychiatry. 2015;5:e623.
Flores G, Barbeau D, Quirion R, Srivastava LK. Decreased binding of dopamine d3 receptors in limbic subregions after neonatal bilateral lesion of rat hippocampus. J Neurosci. 1996;16:2020–6.
Schmauss C, Haroutunian V, Davis KL, Davidson M. Selective loss of dopamine d3-type receptor mrna expression in parietal and motor cortices of patients with chronic schizophrenia. Proc Natl Acad Sci U S A. 1993;90:8942–6.
Zvara A, Szekeres G, Janka Z, Kelemen JZ, Cimmer C, Santha M, Puskas LG. Over-expression of dopamine d2 receptor and inwardly rectifying potassium channel genes in drug-naive schizophrenic peripheral blood lymphocytes as potential diagnostic markers. Dis Markers. 2005;21:61–9.
Kurian SM, Le-Niculescu H, Patel SD, Bertram D, Davis J, Dike C, Yehyawi N, Lysaker P, Dustin J, Caligiuri M, et al. Identification of blood biomarkers for psychosis using convergent functional genomics. Mol Psychiatry. 2011;16:37–58.
Liu L, Yuan G, Cheng Z, Zhang G, Liu X, Zhang H. Identification of the mrna expression status of the dopamine d2 receptor and dopamine transporter in peripheral blood lymphocytes of schizophrenia patients. PLoS One. 2013;8:e75259.
Kirillova GP, Hrutkay RJ, Shurin MR, Shurin GV, Tourkova IL, Vanyukov MM. Dopamine receptors in human lymphocytes: Radioligand binding and quantitative rt-pcr assays. J Neurosci Methods. 2008;174:272–80.
Zhan L, Kerr JR, Lafuente MJ, Maclean A, Chibalina MV, Liu B, Burke B, Bevan S, Nasir J. Altered expression and coregulation of dopamine signalling genes in schizophrenia and bipolar disorder. Neuropathol Appl Neurobiol. 2011;37:206–19.