A PRELIMINARY INVESTIGATION OF HTR1A GENE EXPRESSION LEVELS IN AUTISM SPECTRUM DISORDERS
Objective: This study was conducted to explore the expression levels of HTR1A gene in a sample of Egyptian autistic children.
Methods: Thirty autistic patients (18 boys, 12 girls) and 20 controls were enrolled in the study. From each child, we isolated RNA samples from whole blood. Quantitative Real-Time PCR (qRT-PCR) was used to measure the gene expressions of HTR1A and normalized to the house keeping gene, beta-actin.
Results: The HTR1A gene expression of healthy controls and ASD subjects were varied significantly (p =0.0062). As compared to control healthy subjects, the HTR1A expressions were greatly reduced in samples of ASD.
Conclusion: HTR1A gene expression level is a candidate gene for further studies to explore its potential roles in ASD related pathways.
2. Hervas A, Toma C, Romaris P, Ribases M, Salgado M, Bayes M, et al. The involvement of serotonin polymorphisms in autistic spectrum symptomatology. Psychiatric Genetics 2014;24:158-63.
3. Vijayashankar S, Doss U, Damodaran LPM, Arumugam G, Sridharan S. Analysis of salivary components to evaluate the pathogenesis of autism in children. Asian J Pharm Clin Res 2014;7:205-11.
4. Jafurulla MD, Bandar S, Pucadyil TJ, Chattopadhyay A. Sphingolipids modulate the function of human serotonin 1A receptors: Insights from sphingolipid-deficient cells. Biochim Biophys Acta 2017;1859:598-4.
5. Fiorino B, Severino E, Magli A, Ciano G, Caliendo Y, Santagada F, et al. 5-HT1A receptor: an old target as a new attractive tool in drug discovery from central nervous system to cancer. J Med Chem 2014;57:4407-26.
6. Zafeiriou DI, Ververi A, Vargiami E. The serotonergic system: its role in pathogenesis and early developmental treatment of autism. Curr Neuropharmacol 2009;7:150-7.
7. Hammock E, Veenstra Vanderweele J, Yan Z, Kerr TM, Morris M, Anderso GM, et al. Examining autism spectrum disorders by biomarkers: example from the oxytocin and serotonin systems. J Am Acad Child Adolesc Psychiatry 2012;51:712-21.
8. Misane I, Ogren SO. Selective 5-HT1A antagonists WAY 100635 and NAD-299 attenuate the impairment of passive avoidance caused by scopolamine in the rat. Neuropsychopharmacology 2003;28:253-64.
9. Whitaker Azmitia PM. Serotinin and brain development: role of in human developmental diseases. Brain Res Bull 2001;56:479-85.
10. Albert PR, LeFrancois B, Miller AM. Transcriptional dysregulation of 5-HT1A autoreceptors in mental illness. Molecular Brain 2011;4:21-35.
11. Sener EF, Uytun M, Bayramov KK, Zarasiz C, Oztop DB, Canatan H, et al. The roles of CC2D1A and HTR1A gene expressions in autism spectrum disorders. Metab Brain Dis 2016;31:613-9.
12. Hettema JM, An SS, van den Oord EJCG, Neale MC, Kendler KS, Chen X. Association study between the serotonin 1A receptor HTR1A gene and neuroticism, major depression, and anxiety disorders. Am J Med Gen Neuropsychiatry Genet 2008;147B:661-6.
13. Gross C, Santarelli L, Brunner D, Zhuang X, Hen R. Altered fear circuits in 5-HT (1A) receptor KO mice. Biol Psychiatry 2000;48:1157-63.
14. Brune CW, Kim SJ, Leventhal BL, Lord C, Cook EH. 5-HTTLPR genotype-specific phenotypes in children and adolescents with autism. Am J Psychiatry 2006;163:2148-56.
15. Haddjeri N, Blier P, De Montigny C. Long-term antidepressant treatments result in tonic activation of forebrain 5HT1A receptors. J Neurosci 1998;18:10150-6.
16. Zhang X, Gainetdinov RP, Beaulieu JM, Sotnikova ID, Burch LH, Williams RB, et al. Loss of function mutation in tryptophan hydroxylase-2 identified in unipolar major depression. Neuron 2005;45:11-6.
17. Lemonde S, Rogaeva A, Albert PR. Cell type-dependent recruitment of trichostain A-sensitive repression of the human 5-HT1A receptor gene. Neurochem 2004;88:857-68.
18. Ou MX, Jafar Nejad H, Storring JM, Lemonde S, Albert FR. Novel dual repressor elements for neuronal cell-specific transcription of the rat 5-HT1A receptor gene. J Biol Chem 2000;275:8161-3.
19. Martin Ruiz R, Puig MV, Celada P, Shapiro DA, Roth BL, Mengod G, et al. Control of serotonergic function in medial prefrontal cortex by serotonin-2A receptors through a glutamate-dependent mechanism. J Neurosci 2001;21:9856-66.
20. Sakau M, Somboonthum P, Nishihara B, Koyama Y, Hashimoto H, Baba A, et al. Postsynaptic 5-hydroxytryptamine (1A) receptor activation increases in vivo dopamine release in rat prefrontal cortex. J Pharmacol 2000;129:1028-34.
21. Diaz Mataix L, Scorza MC, Bortolozzi A, Toth M, Celada P, Artigas F. Involvement of 5-HT1A receptors in prefrontal cortex in the modulation of dopaminergic activity: role in atypical antipsychotic action. J Neurosci 2005;25:10831-43.
22. Diaz Mataix L, Artigas F, Celada P. Activation of pyramidal cells in rat medial prefrontal cortex projecting to ventral tegmental area by a 5-HT1A receptor agonist. Eur Neuropsychopharmacol 2006;16:288-96.
23. Polter AM. 5-HT1A receptor-regulated signal transduction pathways in brain. Cell Signal 2010;22:1406-12.
24. Albert PR, Lembo P, Storring JM, Charest A, Saucier C. The 5-HT1A receptor: signaling desensitization and gene transcription. Neuropsychopharmacology 1996;14:19-25.
25. Berney A, Nishikawa M, Benkelfat C, Debonnel G, Diksrc M. An index of 5-HT synthesis changes during early antidepressant treatment alpha-Cmetyl-l-tryptophan PET study. Neurochem Int 2008;52:701-8.
26. Frey BN, Rosa Neto P, Lubarsky S, Diksic M. Correlation between serotonin synthesis and 5-HT1A receptor binding in the living human brain: a combined alpha-[11CJMT] and [18F] MPPF position emission tomography study. Neuroimage 2008;42:850-7.
27. Richardson Jones JW, Craige CP, Guiard BP, Stephen A, Metzeger KL, Kung HF, et al. 5HT1A autoreceptor levels determine vulnerability to stress and response to antidepressants. Neuron 2010;65:40-52.
28. Storring JM, Charest A, Cheng P, Albert PR. TATA-driven transcriptional initiation and regulation of the rat serotonin 5-HT1A receptor gene. Neurochem 1999;72:2238-47.
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