Abstract
The serotoninergic system plays a key role in environmental sensitivity, potentially through down-stream effects on the GABAergic and glutamatergic systems. We previously demonstrated that juvenile serotonin transporter knockout (SERT−/−) rats, showing increased environmental sensitivity, exhibit a decreased GABA-mediated inhibitory tone in the cortex. Since the GABAergic and glutamatergic systems are tightly interconnected, we here analyzed glutamatergic markers in the prefrontal cortex of SERT−/− rats, from the early stages of life until adulthood. We found that SERT inactivation in pre-weaning, juvenile, and adult rats was associated with reduced expression of proteins essential for the glutamatergic synapses such as GluN1, PSD95, CDC42, and SEPT7. These lifelong molecular changes may destabilize glutamatergic signaling and possibly contribute to stress sensitivity and vulnerability to stress-related disorders associated with SERT alteration.
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Acknowledgements
PB was supported by cycle XXXI of the doctorate in Experimental and Clinical Pharmacological Sciences, Department of Pharmacological and Biomolecular Sciences, Universita’ degli Studi di Milano. This work is furthermore supported by and the ERANID Grant “STANDUP” and the ERANET Grant “RESPOND” awarded to JH.
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FC, JRH, and MAR and were responsible for the study concept and design. PB performed and analyzed the molecular analysis. Data analysis and interpretation were done by PB, FC, JRH, and MAR. PB drafted the manuscript and FC and JRH critically revised the manuscript.
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M.A.R. has received compensation as speaker/consultant from Lundbeck, Otzuka, Sumitomo Dainippon Pharma and Sunovion, and he has received research grants from Lundbeck, Sumitomo Dainippon Pharma and Sunovion. F.C., P.B., and J.R.H. have nothing to declare.
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All procedures used in this study were compliant with the rules and principles of the 2010/63/EU Directive and were approved by the Committee for Animal Experiments of the Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
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Brivio, P., Homberg, J.R., Riva, M.A. et al. Alterations of Glutamatergic Markers in the Prefrontal Cortex of Serotonin Transporter Knockout Rats: A Developmental Timeline. Cell Mol Neurobiol 39, 715–720 (2019). https://doi.org/10.1007/s10571-019-00673-9
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DOI: https://doi.org/10.1007/s10571-019-00673-9