Back to Search
Start Over
Prenatal poly I:C age-dependently alters cannabinoid type 1 receptors in offspring: a longitudinal small animal PET study using [(18)F]MK-9470.
- Source :
-
Experimental neurology [Exp Neurol] 2014 Jul; Vol. 257, pp. 162-9. Date of Electronic Publication: 2014 May 10. - Publication Year :
- 2014
-
Abstract
- Evidence 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 [(18)F]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) (4mg/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.<br /> (Copyright © 2014 Elsevier Inc. All rights reserved.)
- Subjects :
- Age Factors
Animals
Body Weight drug effects
Brain Mapping
Disease Models, Animal
Female
Gene Expression Regulation, Developmental drug effects
Magnetic Resonance Imaging
Male
Positron-Emission Tomography
Pregnancy
Protein Binding drug effects
Pyridines pharmacokinetics
Rats
Rats, Wistar
Receptor, Cannabinoid, CB1 metabolism
Brain diagnostic imaging
Brain drug effects
Brain growth & development
Gene Expression Regulation, Developmental physiology
Poly I-C pharmacology
Prenatal Exposure Delayed Effects physiopathology
Receptor, Cannabinoid, CB1 drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 1090-2430
- Volume :
- 257
- Database :
- MEDLINE
- Journal :
- Experimental neurology
- Publication Type :
- Academic Journal
- Accession number :
- 24825369
- Full Text :
- https://doi.org/10.1016/j.expneurol.2014.05.004