CRIP1a switches cannabinoid receptor agonist/antagonist-mediated protection from glutamate excitotoxicity

A shared pathology among many neurological and neurodegenerative disorders is neuronal loss. Cannabinoids have been shown to be neuroprotective in multiple systems. However, both agonists and antagonists of the CB1 cannabinoid receptor are neuroprotective, but the mechanisms responsible for these actions remain unclear. Recently a CB1 receptor interacting protein, CRIP1a, was identified and found to alter CB1 activity. Here we show that in an assay of glutamate neurotoxicity in primary neuronal cortical cultures CRIP1a disrupts agonist-induced neuroprotection and confers antagonist-induced neuroprotection.

► CB1 is expressed in embryonic cortical neurons in vitro and in vivo.
► CRIP1a mRNA and protein are expressed in cortical neurons in vitro and in vivo.
► CRIP1a, CB1 agonist, and CB1 antagonist did not alter basal neuronal cell death.
► CRIP1a reversed CB1 agonist mediated neuroprotection from glutamate excitotoxicity.
► CRIP1a conferred to a CB1 antagonist neuroprotection from glutamate excitotoxicity.