title: Altered relaxin family receptors RXFP1 and RXFP3 in the neocortex of depressed Alzheimer's disease patients.
abstract: BACKGROUND
  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.
  
  
  OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: 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.
authors.forename: Jasinda H
authors.initials: JH
authors.lastname: Lee
authors.affiliation: 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.
authors.forename: Shu Qing
authors.initials: SQ
authors.lastname: Koh
authors.affiliation: Wolfson Centre for Age-Related Diseases, King's College London, London, UK.
authors.forename: Simone
authors.initials: S
authors.lastname: Guadagna
authors.affiliation: Wolfson Centre for Age-Related Diseases, King's College London, London, UK.
authors.forename: Paul T
authors.initials: PT
authors.lastname: Francis
authors.affiliation: Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK.
authors.forename: Margaret M
authors.initials: MM
authors.lastname: Esiri
authors.affiliation: 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.
authors.forename: Christopher P
authors.initials: CP
authors.lastname: Chen
authors.affiliation: 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.
authors.forename: Peter T-H
authors.initials: PT
authors.lastname: Wong
authors.affiliation: 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.|Neurobiology and Ageing Programme, Life Science Institute, National University of Singapore, Kent Ridge, Singapore.|Singapore Institute for Neurotechnology (SINAPSE), Kent Ridge, Singapore.
authors.forename: Gavin S
authors.initials: GS
authors.lastname: Dawe
authors.affiliation: 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. mitchell.lai@dementia-research.org.|Wolfson Centre for Age-Related Diseases, King's College London, London, UK. mitchell.lai@dementia-research.org.|Neurobiology and Ageing Programme, Life Science Institute, National University of Singapore, Kent Ridge, Singapore. mitchell.lai@dementia-research.org.
authors.forename: Mitchell K P
authors.initials: MK
authors.lastname: Lai
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology; D015415:Biomarkers / Q000032:analysis / Q000378:metabolism; D015331:Cohort Studies; D003863:Depression / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005500:Follow-Up Studies; D057809:HEK293 Cells; D006801:Humans; D008297:Male; D019579:Neocortex / Q000737:chemistry / Q000378:metabolism* / Q000473:pathology; D043562:Receptors, G-Protein-Coupled / Q000032:analysis / Q000378:metabolism*; D018000:Receptors, Peptide / Q000032:analysis / Q000378:metabolism*; D012065:Relaxin / Q000032:analysis / Q000378:metabolism
chemical_list: D015415:Biomarkers; C417543:RXFP1 protein, human; C410092:RXFP3 protein, human; D043562:Receptors, G-Protein-Coupled; D018000:Receptors, Peptide; D012065:Relaxin
keywords: Alzheimer’s disease; Dementia; Depression; RXFP1 receptors; RXFP3 receptors; Relaxin family peptides