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Differential involvement of hippocampal serotonin1A receptors and re-uptake sites in non-cognitive behaviors of Alzheimer’s disease

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Abstract

Rationale

Previous studies have shown extensive serotonergic deficits in the hippocampus of Alzheimer’s disease (AD) patients. However, it is unclear whether such deficits play a role in non-cognitive, neuropsychiatric behaviors that occur frequently in AD and cause significant caregiver distress.

Objectives

In this study, we aimed to correlate serotonergic markers in the AD hippocampus with neuropsychiatric behaviors.

Methods

Using postmortem hippocampal homogenates from aged controls as well as a cohort of longitudinally assessed AD patients, measurements of 5-HT1A receptors, 5-HT2A receptors, and serotonin re-uptake (5-HTT) sites were performed by binding with 3H-labeled 8-OH-DPAT, ketanserin, and citalopram, respectively.

Results

Alterations of 5-HT1A receptors and 5-HTT were found to be differentially involved in neuropsychiatric behaviors, with loss of 5-HT1A receptors specifically correlated with depressive symptoms, while 5-HTT sites were preserved or up-regulated in patients with aggressive behaviors.

Conclusions

Our data suggest that neuropsychiatric behaviors in AD share certain neurochemical features with psychiatric disorders like major depression and that serotonergic drugs used in psychiatric disorders may also be efficacious against behavioral symptoms in AD.

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Acknowledgments

The authors would like to acknowledge Dr. J Keene and Prof. T Hope for providing clinical data. This study was supported by a center grant (NMRC/CG/NUHS/2010) from the National Medical Research Council of Singapore to MKP Lai, PTH Wong and CP Chen, as well as a faculty start-up grant to CP Chen by the Yong Loo Lin School of Medicine, National University of Singapore. MKP Lai would like to thank Yung-Yueh Lai for helpful interactions.

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Authors and Affiliations

  1. Memory, Aging and Cognition Centre, National University Health System, Kent Ridge, 117597, Singapore

    Mitchell K. P. Lai, Peter T.-H. Wong & Christopher P. Chen

  2. Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Kent Ridge, 117597, Singapore

    Mitchell K. P. Lai, Shirley W. Tsang, Peter T.-H. Wong & Christopher P. Chen

  3. Department of Clinical Neurology and Neuropathology, John Radcliffe Hospital, University of Oxford, OX3 9DU, Oxford, UK

    Margaret M. Esiri

  4. Wolfson Centre for Age Related Diseases, King’s College London, SE1 1UL, London, UK

    Paul T. Francis

Authors
  1. Mitchell K. P. Lai
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  2. Shirley W. Tsang
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  3. Margaret M. Esiri
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  4. Paul T. Francis
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  5. Peter T.-H. Wong
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  6. Christopher P. Chen
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Corresponding author

Correspondence to Mitchell K. P. Lai.

Electronic supplementary materials

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Supplementary Table S1

Effects of psychotropic medication on hippocampal serotonergic variables in a cohort of AD patients (DOC 35 kb)

Supplementary Figure S1

Loss of median raphe neuronal densities in a cohort of AD patients (DOC 97 kb)

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Lai, M.K.P., Tsang, S.W., Esiri, M.M. et al. Differential involvement of hippocampal serotonin1A receptors and re-uptake sites in non-cognitive behaviors of Alzheimer’s disease. Psychopharmacology 213, 431–439 (2011). https://doi.org/10.1007/s00213-010-1936-2

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  • DOI: https://doi.org/10.1007/s00213-010-1936-2

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