Jasinda H Lee1, Shu Qing Koh1, Simone Guadagna2, Paul T Francis2, Margaret M Esiri3, Christopher P Chen1, Peter T-H Wong1, Gavin S Dawe1,4,5, Mitchell K P Lai6,7,8. 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. 2. Wolfson Centre for Age-Related Diseases, King's College London, London, UK. 3. Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK. 4. Neurobiology and Ageing Programme, Life Science Institute, National University of Singapore, Kent Ridge, Singapore. 5. Singapore Institute for Neurotechnology (SINAPSE), Kent Ridge, Singapore. 6. 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. 7. Wolfson Centre for Age-Related Diseases, King's College London, London, UK. mitchell.lai@dementia-research.org. 8. Neurobiology and Ageing Programme, Life Science Institute, National University of Singapore, Kent Ridge, Singapore. mitchell.lai@dementia-research.org.
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.
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.
Authors: Paul B Rosenberg; Lea T Drye; Barbara K Martin; Constantine Frangakis; Jacobo E Mintzer; Daniel Weintraub; Anton P Porsteinsson; Lon S Schneider; Peter V Rabins; Cynthia A Munro; Curtis L Meinert; Constantine G Lyketsos Journal: Am J Geriatr Psychiatry Date: 2010-02 Impact factor: 4.105
Authors: Craig M Smith; Pei-Juan Shen; Avantika Banerjee; Pascal Bonaventure; Sherie Ma; Ross A D Bathgate; Steven W Sutton; Andrew L Gundlach Journal: J Comp Neurol Date: 2010-10-01 Impact factor: 3.215