Functional Autoradiography Shows Unaltered Cannabinoid CB1 Receptor Signalling in Hippocampus and Cortex of APP/PS1 Transgenic Mice

Title:Functional Autoradiography Shows Unaltered Cannabinoid CB1 Receptor Signalling in Hippocampus and Cortex of APP/PS1 Transgenic Mice

Volume: 11 Issue: 8

Author(s): E. Karkkainen, H. Tanila and J. T. Laitinen

Affiliation:

Keywords: Alzheimers disease, cannabinoid signalling, CB1 receptor, endocannabinoid, [35S]GTPγS autoradiography, APPswe, PS1dE9.

Abstract: The cannabinoid CB1-receptor is among the most abundant G-protein-coupled receptors in the mammalian brain. Whereas post-mortem studies in Alzheimer´s disease (AD) brains compared to age-matched controls have reported decreased CB1-receptor binding but no change in their protein levels (immunoreactivity), decreased or increased CB1- receptor protein levels have been reported in APP/PS1 transgenic mice modelling AD. To complete the picture, the present study used functional autoradiography to assess CB1-receptor-dependent Gi protein activation in the hippocampus, entorhinal cortex and medial frontal cortex of 13- to14-month-old female APPswe/PS1dE9 transgenic and wild-type littermate control mice. The mouse brains were processed for [35S]GTPλS autoradiography so that brain sections were analysed in pairs of one transgenic and one control mouse brain. The autoradiography protocol was completed for each pair both in the absence and presence of dithiotreitol (DTT) to reveal possible redox-dependent alterations in CB1 receptor function. Five treatments were used: baseline, incubation with 10 μM GTPλS to assess nonspecific binding, and CB1 receptor agonist CP55,940 in three concentrations.

Cite this article as:

Karkkainen E., Tanila H. and T. Laitinen J., Functional Autoradiography Shows Unaltered Cannabinoid CB1 Receptor Signalling in Hippocampus and Cortex of APP/PS1 Transgenic Mice, CNS & Neurological Disorders - Drug Targets 2012; 11 (8) . https://dx.doi.org/10.2174/1871527311211080014