Altered Sigma-1 Receptor Expression in Two Animal Models of Cognitive Impairment

Nisha Kuzhuppilly Ramakrishnan, Krisztina Marosi, Csaba J. Nyakas, Chantal Kwizera, Philip H. Elsinga, Kiichi Ishiwata, Paul G M Luiten, Rudi A. J. O. Dierckx, Aren van Waarde*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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Abstract

PURPOSE: Sigma-1 receptors are involved in learning and memory processes. We assessed sigma-1 receptor expression and memory function in two animal models of cognitive impairment.

PROCEDURES: Male Wistar-Hannover rats were either lesioned by unilateral injection of N-methyl-D-aspartic acid in the nucleus basalis, or deprived of rapid eye movement sleep for 48 h, using the modified multiple platform method. Sigma-1 receptor expression was examined with the positron emission tomography radiotracer [(11)C]SA4503, immunohistochemistry, and Western blotting.

RESULTS: Cortical tracer uptake after 1 week was not significantly affected by lesioning. Immunohistochemistry revealed moderate increases of sigma-1 receptors at bregma level -2.8, in parietal cortex layer V of the lesioned hemisphere. Sleep deprivation lowered passive avoidance test scores and reduced [(11)C]SA4503 accumulation and sigma-1 receptor expression in pons.

CONCLUSIONS: Cholinergic lesioning causes an increase of sigma-1 receptor expression in a small cortical area which may be neuroprotective. Sleep deprivation decreases receptor expression in midbrain and pons.

Original languageEnglish
Pages (from-to)231-238
Number of pages8
JournalMolecular Imaging and Biology
Volume17
Issue number2
DOIs
Publication statusPublished - Apr-2015

Keywords

  • Cholinergic lesion
  • microPET
  • Novel object recognition
  • Passive avoidance
  • REM sleep deprivation
  • [C-11]SA4503
  • Sigma-1 receptor
  • NUCLEUS BASALIS MAGNOCELLULARIS
  • SELECTIVE CHOLINERGIC LESION
  • UNFOLDED PROTEIN RESPONSE
  • EYE-MOVEMENT SLEEP
  • INDUCED CELL-DEATH
  • REM-SLEEP
  • RAT-BRAIN
  • DONEPEZIL
  • DEPRIVATION
  • MICE

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