Sigma-1 agonist binding in the aging rat brain: A microPET study with [11C]SA4503

Nisha Kuzhuppilly Ramakrishnan, Anniek Visser, Anna Rybczynska, Csaba Nyakas, Paulus Luiten, Chantal Kwizera, Jurgen Sijbesma, Philippus Elsinga, Kiichi Ishiwata, Rudi Dierckx, Aren van Waarde*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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Abstract

Sigma-1 receptor ligands modulate the release of several neurotransmitters and intracellular calcium signaling. We examined the binding of a radiolabeled sigma-1 agonist in the aging rat brain with positron emission tomography (PET).

Time-dependent uptake of [C-11]SA4503 was measured in the brain of young (1.5 to 3 months) and aged (18 to 32 months) Wistar Hannover rats, and tracer-kinetic models were fitted to this data, using metabolite-corrected plasma radioactivity as input function.

In aged animals, the injected probe was less rapidly metabolized and cleared. Logan graphical analysis and a 2-tissue compartment model (2-TCM) fit indicated changes of total distribution volume (V (T)) and binding potential (BP (ND)) of the tracer. BP (ND) was reduced particularly in the (hypo)thalamus, pons, and medulla.

Some areas showed reductions of ligand binding with aging whereas binding in other areas (cortex) was not significantly affected.

Original languageEnglish
Pages (from-to)588-597
Number of pages10
JournalMolecular Imaging and Biology
Volume18
Issue number4
DOIs
Publication statusPublished - Aug-2016

Keywords

  • Senescence
  • Sigma-1 receptor
  • Agonist binding
  • Positron emission tomography
  • Kinetic modeling
  • Brainstem
  • Hypothalamus
  • EXTRACELLULAR ACETYLCHOLINE LEVEL
  • SPONTANEOUS GLUTAMATE RELEASE
  • POSITRON-EMISSION-TOMOGRAPHY
  • CENTRAL-NERVOUS-SYSTEM
  • AGE-RELATED-CHANGES
  • RECEPTOR LIGANDS
  • PRELIMBIC CORTEX
  • FRONTAL-CORTEX
  • IN-VIVO
  • SITES

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