The effects of testosterone on gene expression of cell-adhesion molecules and scaffolding proteins: The role of sex in early development.


Journal

Andrologia
ISSN: 1439-0272
Titre abrégé: Andrologia
Pays: Germany
ID NLM: 0423506

Informations de publication

Date de publication:
Oct 2021
Historique:
revised: 28 05 2021
received: 10 03 2021
accepted: 02 06 2021
pubmed: 18 6 2021
medline: 14 9 2021
entrez: 17 6 2021
Statut: ppublish

Résumé

Sex-specific differences in brain plasticity appear to be organised by testosterone, which is particularly important during the early stages of development. The main purpose of the present study was to examine the sex differences in mRNA and protein levels of selected cell-adhesion molecules and scaffolding proteins on postnatal days 5 (P5) and 9 (P9) in the rat hippocampus, as well as evaluate the effects of testosterone treatment (100 nM, 48 hr) on synaptic proteins in SH-SY5Y (neuron-like) and U-87MG (astrocyte-like) cells. The gene expression levels of Neuroligin 3 and 'SH3 and multiple ankyrin repeat domains protein' 1 and 3 (SHANK1 and SHANK3) were significantly lower in males compared to females at P5. At P9, a similar significant trend towards a decrease in mRNA expression and protein levels of SHANK3 was found in males. Testosterone treatment induced a significant decrease of Neuroligin 1-3 mRNA expression in both SH-SY5Y and U-87MG cells. SHANK1 and SHANK3 mRNA levels significantly decreased in U-87MG cells response to testosterone presence. The presented results demonstrate that the association of selected postsynaptic cell-adhesion molecules and scaffolding proteins is sex-related. Testosterone appears to be particularly involved in the developmental mechanisms related to neuroplasticity.

Identifiants

pubmed: 34138481
doi: 10.1111/and.14153
doi:

Substances chimiques

RNA, Messenger 0
Testosterone 3XMK78S47O

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

e14153

Subventions

Organisme : Grant Agency of the Ministry of Education and the Slovak Academy of Sciences
ID : VEGA 2/0155/20

Informations de copyright

© 2021 Wiley-VCH GmbH.

Références

Bakos, J., Hlavacova, N., Rajman, M., Ondicova, K., Koros, C., Kitraki, E., Steinbusch, H. W., & Jezova, D. (2009). Enriched environment influences hormonal status and hippocampal brain derived neurotrophic factor in a sex dependent manner. Neuroscience, 164(2), 788-797. https://doi.org/10.1016/j.neuroscience.2009.08.054
Baron-Cohen, S. (2002). The extreme male brain theory of autism. Trends in Cognitive Sciences, 6(6), 248-254. https://doi.org/10.1016/s1364-6613(02)01904-6
Berkel, S., Eltokhi, A., Fröhlich, H., Porras-Gonzalez, D., Rafiullah, R., Sprengel, R., & Rappold, G. A. (2018). Sex hormones regulate SHANK expression. Frontiers in Molecular Neuroscience, 11, 337. https://doi.org/10.3389/fnmol.2018.00337
Bowers, J. M., Waddell, J., & McCarthy, M. M. (2010). A developmental sex difference in hippocampal neurogenesis is mediated by endogenous oestradiol. Biology of Sex Differences, 1(1), 8. https://doi.org/10.1186/2042-6410-1-8
Bramble, M. S., Roach, L., Lipson, A., Vashist, N., Eskin, A., Ngun, T., Gosschalk, J. E., Klein, S., Barseghyan, H., Arboleda, V. A., & Vilain, E. (2016). Sex-specific effects of testosterone on the sexually dimorphic transcriptome and epigenome of embryonic neural stem/progenitor cells. Scientific Reports, 6, 36916. https://doi.org/10.1038/srep36916
Chiocchetti, A. G., Haslinger, D., Stein, J. L., de la Torre-Ubieta, L., Cocchi, E., Rothämel, T., Lindlar, S., Waltes, R., Fulda, S., Geschwind, D. H., & Freitag, C. M. (2016). Transcriptomic signatures of neuronal differentiation and their association with risk genes for autism spectrum and related neuropsychiatric disorders. Translational Psychiatry, 6(8), e864. https://doi.org/10.1038/tp.2016.119
Clarkson, J., & Herbison, A. E. (2016). Hypothalamic control of the male neonatal testosterone surge. Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences, 371(1688), 20150115. https://doi.org/10.1098/rstb.2015.0115
Duerden, E. G., Chakravarty, M. M., Lerch, J. P., & Taylor, M. J. (2020). Sex-based differences in cortical and subcortical development in 436 individuals aged 4-54 years. Cerebral Cortex, 30(5), 2854-2866. https://doi.org/10.1093/cercor/bhz279
Fombonne, E. (2009). Epidemiology of pervasive developmental disorders. Pediatric Research, 65(6), 591-598. https://doi.org/10.1203/PDR.0b013e31819e7203
Gao, S., Fei, M., Cheng, C., Yu, X., Chen, M., Shi, S., Qin, J., Guo, Z., & Shen, A. (2008). Spatiotemporal expression of PSD-95 and nNOS after rat sciatic nerve injury. Neurochemical Research, 33(6), 1090-1100. https://doi.org/10.1007/s11064-007-9555-y
Gehrand, A. L., Phillips, J., Malott, K., & Raff, H. (2020). Corticosterone, adrenal, and the pituitary-gonadal axis in neonatal rats: Effect of maternal separation and hypoxia. Endocrinology, 161(7), bqaa085. https://doi.org/10.1210/endocr/bqaa085
Grassi, D., Bellini, M. J., Acaz-Fonseca, E., Panzica, G., & Garcia-Segura, L. M. (2013). Estradiol and testosterone regulate arginine-vasopressin expression in SH-SY5Y human female neuroblastoma cells through estrogen receptors-α and -β. Endocrinology, 154(6), 2092-2100. https://doi.org/10.1210/en.2012-2137
Guo, G., Kang, L., Geng, D., Han, S., Li, S., Du, J., Wang, C., & Cui, H. (2020). Testosterone modulates structural synaptic plasticity of primary cultured hippocampal neurons through ERK - CREB signalling pathways. Molecular and Cellular Endocrinology, 503, 110671. https://doi.org/10.1016/j.mce.2019.110671
Hashemi, A., Roohvand, F., & Ghahremani, M. H. (2012). Selection of valid reference genes for expression studies of hepatic cell lines under IFN-α treatment. Biochemical and Biophysical Research Communications, 426(4), 649-653. https://doi.org/10.1016/j.bbrc.2012.09.009
Hill, R. A., Klug, M., Kiss Von Soly, S., Binder, M. D., Hannan, A. J., & van den Buuse, M. (2014). Sex-specific disruptions in spatial memory and anhedonia in a "two hit" rat model correspond with alterations in hippocampal brain-derived neurotrophic factor expression and signaling. Hippocampus, 24(10), 1197-1211. https://doi.org/10.1002/hipo.22302
Hillerer, K. M., Slattery, D. A., & Pletzer, B. (2019). Neurobiological mechanisms underlying sex-related differences in stress-related disorders: Effects of neuroactive steroids on the hippocampus. Frontiers in Neuroendocrinology, 55, 100796. https://doi.org/10.1016/j.yfrne.2019.100796
Hyer, M. M., Phillips, L. L., & Neigh, G. N. (2018). Sex Differences in synaptic plasticity: Hormones and beyond. Frontiers in Molecular Neuroscience, 11, 266. https://doi.org/10.3389/fnmol.2018.00266
Jeong, J., Pandey, S., Li, Y., Badger, J. D. 2nd, Lu, W., & Roche, K. W. (2019). PSD-95 binding dynamically regulates NLGN1 trafficking and function. Proceedings of the National Academy of Sciences of the United States of America, 116(24), 12035-12044. https://doi.org/10.1073/pnas.1821775116
Kight, K. E., & McCarthy, M. M. (2017). Sex differences and estrogen regulation of BDNF gene expression, but not propeptide content, in the developing hippocampus. Journal of Neuroscience Research, 95(1-2), 345-354. https://doi.org/10.1002/jnr.23920
Kight, K. E., & McCarthy, M. M. (2020). Androgens and the developing hippocampus. Biology of Sex Differences, 11(1), 30. https://doi.org/10.1186/s13293-020-00307-6
Konopka, G., Wexler, E., Rosen, E., Mukamel, Z., Osborn, G. E., Chen, L., Lu, D., Gao, F., Gao, K., Lowe, J. K., & Geschwind, D. H. (2012). Modeling the functional genomics of autism using human neurons. Molecular Psychiatry, 17(2), 202-214. https://doi.org/10.1038/mp.2011.60
Koss, W. A., & Frick, K. M. (2017). Sex differences in hippocampal function. Journal of Neuroscience Research, 95(1-2), 539-562. https://doi.org/10.1002/jnr.23864
Lau, C. F., Ho, Y. S., Hung, C. H., Wuwongse, S., Poon, C. H., Chiu, K., Yang, X., Chu, L. W., & Chang, R. C. (2014). Protective effects of testosterone on presynaptic terminals against oligomeric β-amyloid peptide in primary culture of hippocampal neurons. BioMed Research International, 2014, https://doi.org/10.1155/2014/103906
Laube, C., van den Bos, W., & Fandakova, Y. (2020). The relationship between pubertal hormones and brain plasticity: Implications for cognitive training in adolescence. Developmental Cognitive Neuroscience, 42, 100753. https://doi.org/10.1016/j.dcn.2020.100753
Laukova, M., Vargovic, P., Rokytova, I., Manz, G., & Kvetnansky, R. (2018). Repeated stress exaggerates lipopolysaccharide-induced inflammatory response in the rat spleen. Cellular and Molecular Neurobiology, 38(1), 195-208. https://doi.org/10.1007/s10571-017-0546-5
Littlejohn, E. L., Fedorchak, S., & Boychuk, C. R. (2020). Sex-steroid-dependent plasticity of brain-stem autonomic circuits. American Journal of Physiology-Regulatory, Integrative and Comparative Physiology, 319(1), R60-R68. https://doi.org/10.1152/ajpregu.00357.2019
Livak, K. J., & Schmittgen, T. D. (2001). Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods (San Diego, Calif.), 25(4), 402-408. https://doi.org/10.1006/meth.2001.1262
Meyer, G., Ferres-Torres, R., & Mas, M. (1978). The effects of puberty and castration on hippocampal dendritic spines of mice. A Golgi study. Brain Research, 155(1), 108-112. https://doi.org/10.1016/0006-8993(78)90309-8
Mizuno, K., Ris, L., Sánchez-Capelo, A., Godaux, E., & Giese, K. P. (2006). Ca2+/calmodulin kinase kinase alpha is dispensable for brain development but is required for distinct memories in male, though not in female, mice. Molecular and Cellular Biology, 26(23), 9094-9104. https://doi.org/10.1128/MCB.01221-06
Nakamura, S., Uenoyama, Y., Ikegami, K., Dai, M., Watanabe, Y., Takahashi, C., Hirabayashi, M., Tsukamura, H., & Maeda, K. I. (2016). Neonatal kisspeptin is steroid-independently required for defeminisation and peripubertal kisspeptin-induced testosterone is required for masculinisation of the brain: A behavioural study using kiss1 knockout rats. Journal of Neuroendocrinology, 28(10), https://doi.org/10.1111/jne.12409
Naskar, S., Narducci, R., Balzani, E., Cwetsch, A. W., Tucci, V., & Cancedda, L. (2019). The development of synaptic transmission is time-locked to early social behaviors in rats. Nature Communications, 10(1), 1195. https://doi.org/10.1038/s41467-019-09156-3
Nava, N., Treccani, G., Müller, H. K., Popoli, M., Wegener, G., & Elfving, B. (2017). The expression of plasticity-related genes in an acute model of stress is modulated by chronic desipramine in a time-dependent manner within medial prefrontal cortex. European Neuropsychopharmacology, 27(1), 19-28. https://doi.org/10.1016/j.euroneuro.2016.11.010
Piechota, M., Korostynski, M., Golda, S., Ficek, J., Jantas, D., Barbara, Z., & Przewlocki, R. (2017). Transcriptional signatures of steroid hormones in the striatal neurons and astrocytes. BMC Neuroscience, 18(1), 37. https://doi.org/10.1186/s12868-017-0352-5
Pillai, A. (2008). Decreased expression of Sprouty2 in the dorsolateral prefrontal cortex in schizophrenia and bipolar disorder: A correlation with BDNF expression. PLoS One, 3(3), e1784. https://doi.org/10.1371/journal.pone.0001784
Qiu, S., Li, Y., Li, Y., Zhong, W., Shi, M., Zhao, Q., Zhang, K., Wang, Y., Lu, M., Zhu, X., Jiang, H., Yu, Y., Cheng, Y., & Liu, Y. (2018). Association between SHANK3 polymorphisms and susceptibility to autism spectrum disorder. Gene, 651, 100-105. https://doi.org/10.1016/j.gene.2018.01.078
Rapanelli, M., Lew, S. E., Frick, L. R., & Zanutto, B. S. (2010). Plasticity in the rat prefrontal cortex: Linking gene expression and an operant learning with a computational theory. PLoS One, 5(1), e8656. https://doi.org/10.1371/journal.pone.0008656
Reichova, A., Bacova, Z., Bukatova, S., Kokavcova, M., Meliskova, V., Frimmel, K., Ostatnikova, D., & Bakos, J. (2020). Abnormal neuronal morphology and altered synaptic proteins are restored by oxytocin in autism-related SHANK3 deficient model. Molecular and Cellular Endocrinology, 518, 110924. https://doi.org/10.1016/j.mce.2020.110924
Ricci, A., Felici, L., Mariotta, S., Mannino, F., Schmid, G., Terzano, C., Cardillo, G., Amenta, F., & Bronzetti, E. (2004). Neurotrophin and neurotrophin receptor protein expression in the human lung. American Journal of Respiratory Cell and Molecular Biology, 30(1), 12-19. https://doi.org/10.1165/rcmb.2002-0110OC
Sacai, H., Sakoori, K., Konno, K., Nagahama, K., Suzuki, H., Watanabe, T., Watanabe, M., Uesaka, N., & Kano, M. (2020). Autism spectrum disorder-like behavior caused by reduced excitatory synaptic transmission in pyramidal neurons of mouse prefrontal cortex. Nature Communications, 11(1), 5140. https://doi.org/10.1038/s41467-020-18861-3
Sarkey, S., Azcoitia, I., Garcia-Segura, L. M., Garcia-Ovejero, D., & DonCarlos, L. L. (2008). Classical androgen receptors in non-classical sites in the brain. Hormones and Behavior, 53(5), 753-764. https://doi.org/10.1016/j.yhbeh.2008.02.015
Sarowar, T., & Grabrucker, A. M. (2016). Actin-dependent alterations of dendritic spine morphology in shankopathies. Neural Plasticity, 2016, 1-15. https://doi.org/10.1155/2016/8051861
Schulz, K. M., & Sisk, C. L. (2016). The organizing actions of adolescent gonadal steroid hormones on brain and behavioral development. Neuroscience and Biobehavioral Reviews, 70, 148-158. https://doi.org/10.1016/j.neubiorev.2016.07.036
Sengupta, P. (2013). The laboratory rat: Relating its age with human's. International Journal of Preventive Medicine, 4(6), 624-630.
Shcheglovitov, A., Shcheglovitova, O., Yazawa, M., Portmann, T., Shu, R., Sebastiano, V., Krawisz, A., Froehlich, W., Bernstein, J. A., Hallmayer, J. F., & Dolmetsch, R. E. (2013). SHANK3 and IGF1 restore synaptic deficits in neurons from 22q13 deletion syndrome patients. Nature, 503(7475), 267-271. https://doi.org/10.1038/nature12618
Suckow, A. T., Comoletti, D., Waldrop, M. A., Mosedale, M., Egodage, S., Taylor, P., & Chessler, S. D. (2008). Expression of neurexin, neuroligin, and their cytoplasmic binding partners in the pancreatic beta-cells and the involvement of neuroligin in insulin secretion. Endocrinology, 149(12), 6006-6017. https://doi.org/10.1210/en.2008-0274
Szapacs, M. E., Mathews, T. A., Tessarollo, L., Ernest Lyons, W., Mamounas, L. A., & Andrews, A. M. (2004). Exploring the relationship between serotonin and brain-derived neurotrophic factor: Analysis of BDNF protein and extraneuronal 5-HT in mice with reduced serotonin transporter or BDNF expression. Journal of Neuroscience Methods, 140(1-2), 81-92. https://doi.org/10.1016/j.jneumeth.2004.03.026
Werling, D. M., & Geschwind, D. H. (2013). Sex differences in autism spectrum disorders. Current Opinion in Neurology, 26(2), 146-153. https://doi.org/10.1097/WCO.0b013e32835ee548
Yi, F., Danko, T., Botelho, S. C., Patzke, C., Pak, C., Wernig, M., & Südhof, T. C. (2016). Autism-associated SHANK3 haploinsufficiency causes Ih channelopathy in human neurons. Science, 352(6286), aaf2669. https://doi.org/10.1126/science.aaf2669
Yu, S., Yang, S., Holsboer, F., Sousa, N., & Almeida, O. F. (2011). Glucocorticoid regulation of astrocytic fate and function. PLoS One, 6(7), e22419. https://doi.org/10.1371/journal.pone.0022419
Zalcman, N., Canello, T., Ovadia, H., Charbit, H., Zelikovitch, B., Mordechai, A., Fellig, Y., Rabani, S., Shahar, T., Lossos, A., & Lavon, I. (2018). Androgen receptor: A potential therapeutic target for glioblastoma. Oncotarget, 9(28), 19980-19993. https://doi.org/10.18632/oncotarget.25007

Auteurs

Annamaria Srancikova (A)

Institute of Experimental Endocrinology, Biomedical Research Center, Slovak Academy of Sciences, Bratislava, Slovakia.

Denisa Mihalj (D)

Institute of Experimental Endocrinology, Biomedical Research Center, Slovak Academy of Sciences, Bratislava, Slovakia.

Zuzana Bacova (Z)

Institute of Experimental Endocrinology, Biomedical Research Center, Slovak Academy of Sciences, Bratislava, Slovakia.

Jan Bakos (J)

Institute of Experimental Endocrinology, Biomedical Research Center, Slovak Academy of Sciences, Bratislava, Slovakia.
Faculty of Medicine, Comenius University, Bratislava, Slovakia.

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