Expression of genes ESR1 and ESR2 encoding estrogen receptors and cognitive functioning in patients with depression
, 1, 1, 2, 1
Streszczenie
Introduction: Researchers are increasingly interested in the role of sex hormones and their impact on other than reproductive systems, including mental functioning. Estrogens acting through the receptors ESR1 and ESR2 may participate in the regulation of mood and cognitive functions. The aim of the study was to evaluate the expression of genes ESR1 and ESR2 encoding estrogen receptors in depressive disorders and search for relationship between gene expression, cognitive functioning and socio-demographic data. Material and methods: A total of 236 people (131 depressed patients, 105 healthy controls) participated in the study. Socio-demographic data were collected. Neuropsychological test have been carried out to evaluatecognitive functions. Venous blood was collected from all participants. RT-PCR was performed to evaluate the expression of genes ESR1 and ESR2 at mRNA level and enzyme-linked immunosorbent assay (ELISA) test to evaluate gene expression at protein level. Results: Participants suffering from depression were characterized by a higher level of ESR1 expression both at the mRNA and protein level. Expression of ESR1 and ESR2 genes might be related to functioning in the examined cognitive areas. Expression of ESR1 and ESR2 genes does not differ statistically significantly in terms of gender. Conclusions: ESR1 and ESR2 genes might play an important role in depression and cognitive functioning.
Słowa kluczowe: depressionestrogen receptorcognitive functionsESR1ESR2
Referencje
- Institute of Health Metrics and Evaluation. Global Health Data Exchange (GHDx). https://vizhub.healthdata.org/gbd-results/ (4.03.2023).
- Zielniok K, Gajewska M, Motyl T. [Molecular actions of 17β-estradiol and progesterone and their relationship with cellular signaling pathways]. Postepy Hig Med Dosw (Online). 2014; 68: 777–792.
- The Human Protein Atlas. ESR1 information. https://www.proteinatlas.org/ENSG00000091831-ESR1 (24.03.2023).
- The Human Protein Atlas. ESR2 information. https://www.proteinatlas.org/ENSG00000140009-ESR2 (24.03.2023).
- Donner N, Handa RJ. Estrogen receptor beta regulates the expression of tryptophan-hydroxylase 2 mRNA within serotonergic neurons of the rat dorsal raphe nuclei. Neuroscience. 2009; 163(2): 705–718.
- Wissink S, van der Burg B, Katzenellenbogen BS, et al. Synergistic activation of the serotonin-1A receptor by nuclear factor-kappa B and estrogen. Mol Endocrinol. 2001; 15(4): 543–552.
- Kalinowski D, Bogus-Nowakowska K, Kozłowska A, et al. Dopaminergic and cholinergic modulation of the amygdala is altered in female mice with oestrogen receptor β deprivation. Sci Rep. 2023; 13(1): 897.
- Almey A, Milner TA, Brake WG. Estrogen receptors in the central nervous system and their implication for dopamine-dependent cognition in females. Horm Behav. 2015; 74: 125–138.
- Weiser MJ, Handa RJ. Estrogen impairs glucocorticoid dependent negative feedback on the hypothalamic-pituitary-adrenal axis via estrogen receptor alpha within the hypothalamus. Neuroscience. 2009; 159(2): 883–895.
- Liu J, Bisschop PH, Eggels L, et al. Intrahypothalamic estradiol modulates hypothalamus-pituitary-adrenal-axis activity in female rats. Endocrinology. 2012; 153(7): 3337–3344.
- Liu F, Day M, Muñiz LC, et al. Activation of estrogen receptor-beta regulates hippocampal synaptic plasticity and improves memory. Nat Neurosci. 2008; 11(3): 334–343.
- Vargas KG, Milic J, Zaciragic A, et al. The functions of estrogen receptor beta in the female brain: A systematic review. Maturitas. 2016; 93: 41–57.
- Jarema M, Dudek D, Czernikiewicz A. [Cognitive dysfunctions in depression — underestimated symptom or new dimension?]. Psychiatr Pol. 2014; 48(6): 1105–1116.
- Livak KJ, Schmittgen TD. 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.
- Golden C, Freshwater S. The Stroop Color and Word Test. Stoelting, Wood Dale 2002.
- Reitan RM. The relation of the trail making test to organic brain damage. J Consult Psychol. 1955; 19(5): 393–394.
- Szepietowska E, Gawda B. Neural mechanisms of semantic and phonemic fluency: fMRI studies. Clinical implications. Polish Psychological Forum. 2016; XXI(2): 170–187.
- Łuria A. Neuropsychologia. PZWL, Warszawa 1976.
- Niknamian S. Relative ESR1 gene expression in major depression a biomarker for hormone therapy. Archieves in Neurology and Neurscience. 2020; 8(4).
- Villa A, Rizzi N, Vegeto E, et al. Estrogen accelerates the resolution of inflammation in macrophagic cells. Sci Rep. 2015; 5: 15224.
- Gaspar HA, Gerring Z, Hübel C, et al. Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium. Using genetic drug-target networks to develop new drug hypotheses for major depressive disorder. Transl Psychiatry. 2019; 9(1): 117.
- Arevalo MA, Santos-Galindo M, Lagunas N, et al. Selective estrogen receptor modulators as brain therapeutic agents. J Mol Endocrinol. 2011; 46(1): R1–R9.
- Liu F, Day M, Muñiz LC, et al. Activation of estrogen receptor-beta regulates hippocampal synaptic plasticity and improves memory. Nat Neurosci. 2008; 11(3): 334–343.
- Rissman EF, Heck AL, Leonard JE, et al. Disruption of estrogen receptor beta gene impairs spatial learning in female mice. Proc Natl Acad Sci U S A. 2002; 99(6): 3996–4001.
- Hutson DD, Gurrala R, Ogola BO, et al. Estrogen receptor profiles across tissues from male and female Rattus norvegicus. Biol Sex Differ. 2019; 10(1): 4.
- Maioli S, Leander K, Nilsson P, et al. Estrogen receptors and the aging brain. Essays Biochem. 2021; 65(6): 913–925.
- Sullivan PF, Fan C, Perou CM. Evaluating the comparability of gene expression in blood and brain. Am J Med Genet B Neuropsychiatr Genet. 2006; 141B(3): 261–268.
- Pop A, Lupu DI, Cherfan J, et al. Estrogenic/antiestrogenic activity of selected selective serotonin reuptake inhibitors. Clujul Med. 2015; 88(3): 381–385.
- Higgins A, Nash M, Lynch AM. Antidepressant-associated sexual dysfunction: impact, effects, and treatment. Drug Healthc Patient Saf. 2010; 2: 141–150.
- Domingues RR, Wiltbank MC, Hernandez LL. The antidepressant fluoxetine (Prozac®) modulates estrogen signaling in the uterus and alters estrous cycles in mice. Mol Cell Endocrinol. 2023; 559: 111783.
