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Altered relaxin family receptors RXFP1 and RXFP3 in the neocortex of depressed Alzheimer’s disease patients

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Abstract

Rationale

The G-protein-coupled relaxin family receptors RXFP1 and RXFP3 are widely expressed in the cortex and are involved in stress responses and memory and emotional processing. However, the identification of these receptors in human cortex and their status in Alzheimer’s disease (AD), which is characterized by both cognitive impairments and neuropsychiatric behaviours, have not been reported.

Objectives

In this study, we characterized RXFP receptors for immunoblotting and measured RXFP1 and RXFP3 immunoreactivities in the postmortem neocortex of AD patients longitudinally assessed for depressive symptoms.

Methods

RXFP1 and RXFP3 antibodies were characterized by immunoblotting with lysates from transfected HEK cells and preadsorption with RXFP3 peptides. Also, postmortem neocortical tissues from behaviourally assessed AD and age-matched controls were processed for immunoblotting with RXFP1 and RXFP3 antibodies.

Results

Compared to controls, putative RXFP1 immunoreactivity was reduced in parietal cortex of non-depressed AD patients but unchanged in depressed patients. Furthermore, putative RXFP3 immunoreactivity was increased only in depressed AD patients. RXFP1 levels in the parietal cortex also correlated with severity of depression symptoms. In contrast, RXFP1 and RXFP3 levels did not correlate with dementia severity or β-amyloid burden.

Conclusion

Alterations of RXFP1 and RXFP3 may be neurochemical markers of depression in AD, and relaxin family receptors warrant further preclinical investigations as possible therapeutic targets for neuropsychiatric symptoms in dementia.

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Acknowledgments

This study was supported by grants from the National Medical Research Council of Singapore (NMRC/CSA/032/2011; NMRC/IRG/1287/2011), Biomedical Research Council, Agency for Science, Technology and Research (BMRC10/21/19/645) and NUSMed (R184-000-223-133). The authors would like to thank Prof. Tony Hope and Dr Janet Keene for the data of clinical assessments.

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Authors and Affiliations

  1. Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Unit 09-01, Centre for Translational Medicine (MD6), 14 Medical Drive, Kent Ridge, 117599, Singapore

    Jasinda H. Lee, Shu Qing Koh, Christopher P. Chen, Peter T.-H. Wong, Gavin S. Dawe & Mitchell K. P. Lai

  2. Wolfson Centre for Age-Related Diseases, King’s College London, London, UK

    Simone Guadagna, Paul T. Francis & Mitchell K. P. Lai

  3. Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK

    Margaret M. Esiri

  4. Neurobiology and Ageing Programme, Life Science Institute, National University of Singapore, Kent Ridge, Singapore

    Gavin S. Dawe & Mitchell K. P. Lai

  5. Singapore Institute for Neurotechnology (SINAPSE), Kent Ridge, Singapore

    Gavin S. Dawe

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  1. Jasinda H. Lee
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  2. Shu Qing Koh
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  3. Simone Guadagna
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  4. Paul T. Francis
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  9. Mitchell K. P. Lai
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Correspondence to Mitchell K. P. Lai.

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Lee, J.H., Koh, S.Q., Guadagna, S. et al. Altered relaxin family receptors RXFP1 and RXFP3 in the neocortex of depressed Alzheimer’s disease patients. Psychopharmacology 233, 591–598 (2016). https://doi.org/10.1007/s00213-015-4131-7

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  • DOI: https://doi.org/10.1007/s00213-015-4131-7

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