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Disruption to the 5-HT7 Receptor Following Hypoxia–Ischemia in the Immature Rodent Brain

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Abstract

It has become increasingly evident the serotonergic (5-hydroxytryptamine, 5-HT) system is an important central neuronal network disrupted following neonatal hypoxic–ischemic (HI) insults. Serotonin acts via a variety of receptor subtypes that are differentially associated with behavioural and cognitive mechanisms. The 5-HT7 receptor is purported to play a key role in epilepsy, anxiety, learning and memory and neuropsychiatric disorders. Furthermore, the 5-HT7 receptor is highly localized in brain regions damaged following neonatal HI insults. Utilising our well-established neonatal HI model in the postnatal day 3 (P3) rat pup we demonstrated a significant decrease in levels of the 5-HT7 protein in the frontal cortex, thalamus and brainstem one week after insult. We also observed a relative decrease in both the cytosolic and membrane fractions of 5-HT7. The 5-HT7 receptor was detected on neurons throughout the cortex and thalamus, and 5-HT cell bodies in the brainstem. However we found no evidence of 5-HT7 co-localisation on microglia or astrocytes. Moreover, minocycline treatment did not significantly prevent the HI-induced reductions in 5-HT7. In conclusion, neonatal HI injury caused significant disruption to 5-HT7 receptors in the forebrain and brainstem. Yet the use of minocycline to inhibit activated microglia, did not prevent the HI-induced changes in 5-HT7 expression.

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Acknowledgements

This work was partially funded by the Royal Brisbane and Women’s Foundation. JAW was supported by an Australian Postgraduate Award. HER was supported by a University of Queensland Research Tuition Award and University of Queensland Scholarship.

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  1. Hanna E. Reinebrant

    Present address: Mater Research Institute, The University of Queensland (MRI-UQ), Brisbane, Australia

Authors and Affiliations

  1. Centre for Clinical Research, Faculty of Medicine, The University of Queensland, Herston, QLD, 4029, Australia

    Julie A. Wixey, Hanna E. Reinebrant, Kirat K. Chand & Kathryn M. Buller

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Wixey, J.A., Reinebrant, H.E., Chand, K.K. et al. Disruption to the 5-HT7 Receptor Following Hypoxia–Ischemia in the Immature Rodent Brain. Neurochem Res 43, 711–720 (2018). https://doi.org/10.1007/s11064-018-2473-3

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