Prenatal poly I:C age-dependently alters cannabinoid type 1 receptors in offspring: a longitudinal small animal PET study using [18F]MK-9470

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dc.contributor.authorVerdurand, Men_AU
dc.contributor.authorDalton, VSen_AU
dc.contributor.authorNguyen, VHen_AU
dc.contributor.authorGrégoire, MCen_AU
dc.contributor.authorZahra, Den_AU
dc.contributor.authorWyatt, NAen_AU
dc.contributor.authorBurgess, Len_AU
dc.contributor.authorGreguric, Ien_AU
dc.contributor.authorZavitsanou, Ken_AU
dc.date.accessioned2018-09-16T22:48:00Zen_AU
dc.date.available2018-09-16T22:48:00Zen_AU
dc.date.issued2014-05-10en_AU
dc.date.statistics2018-07-27en_AU
dc.description.abstractEvidence suggests that there is a link between the endocannabinoid system (ECS) and neuropsychiatric illnesses, including schizophrenia. Whilst the ECS has been shown to be involved in immune system regulation in various ways, it is known that infections during pregnancy can modulate the immune system of the mother and increase the risk for schizophrenia in offspring. In animal studies, maternal immune activation following administration of viral or bacterial mimics has been shown to reproduce many key structural, behavioural, and pharmacological abnormalities in offspring that resemble schizophrenia. In the present study, we used Positron Emission Tomography (PET) and [18F]MK-9470, a selective high-affinity inverse agonist radioligand for cannabinoid type 1 receptors (CB1R), to longitudinally assess CB1R expression in the progeny of female rats exposed to the viral mimic polyriboinosinic–polyribocytidilic acid (poly I:C) (4 mg/kg i.v.) or vehicle at gestational day 15 (GD 15). PET scans were performed in offspring at postnatal days (PND) 32–42 (adolescence) and in the same animals again at PNDs 75–79 (adulthood). Sixteen regions of interest were assessed, encompassing the whole rat brain. At adolescence, offspring exposed prenatally to poly I:C had significantly lower CB1R relative Standard Uptake Values (rSUV) compared to controls in the globus pallidus (p = 0.046). In adulthood, however, poly I:C exposed offspring had higher levels of CB1R rSUV in sensory cortex (p = 0.034) and hypothalamus (p = 0.032) compared to controls. Our results suggest that prenatal poly I:C leads to long term alterations in the integrity of the ECS that are age and region-specific. The increased CB1R expression in adulthood following poly I:C mirrors the increased CB1R observed in patients with schizophrenia in post-mortem and in vivo PET studies. © Elsevieren_AU
dc.identifier.citationVerdurand, M., Dalton, V. S., Nguyen, V., Grégoire, M.-C., Zahra, D., Wyatt, N., Burgess, L., Greguric, I. & Zavitsanou, K. (2014). Prenatal poly I:C age-dependently alters cannabinoid type 1 receptors in offspring: A longitudinal small animal PET study using [18F]MK-9470. Experimental Neurology, 257, 162-169. doi:10.1016/j.expneurol.2014.05.004en_AU
dc.identifier.govdoc9106en_AU
dc.identifier.issn0014-4886en_AU
dc.identifier.journaltitleExperimental Neurologyen_AU
dc.identifier.pagination162-169en_AU
dc.identifier.urihttps://doi.org/10.1016/j.expneurol.2014.05.004en_AU
dc.identifier.urihttp://apo.ansto.gov.au/dspace/handle/10238/8997en_AU
dc.identifier.volume257en_AU
dc.language.isoenen_AU
dc.publisherElsevieren_AU
dc.subjectImmune system diseasesen_AU
dc.subjectMental disordersen_AU
dc.subjectPositron computed tomographyen_AU
dc.subjectReceptorsen_AU
dc.subjectBrainen_AU
dc.subjectIn vivoen_AU
dc.titlePrenatal poly I:C age-dependently alters cannabinoid type 1 receptors in offspring: a longitudinal small animal PET study using [18F]MK-9470en_AU
dc.typeJournal Articleen_AU
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