title: Hypolocomotive behaviour associated with increased microglia in a prenatal immune activation model with relevance to schizophrenia.
abstract: Over the past decade a neurodevelopmental animal model with high validity for schizophrenia has been developed based on the environmental risk factor known as maternal immune activation (MIA). The immunological basis of this model, together with extensive data from clinical and preclinical context, suggests the involvement of an aberrant neuro-immune system in the pathophysiology of schizophrenia. The goal of this study was to examine microglia activation in adult behaviourally phenotyped MIA offspring. MIA was induced in pregnant rats using viral mimetic Poly I:C at gestational day 15. Adult offspring were behaviourally phenotyped at postnatal days (PND) 56, 90 and 180 through the evaluation of prepulse inhibition (PPI) of the acoustic startle and spontaneous locomotion. Finally, the presence of activated microglia in brain regions associated with schizophrenia was evaluated using post-mortem immunohistochemistry against OX-42 (CD11b) and ED-1 (CD68). Although a deficit in PPI could not be replicated despite the high number of animals tested, we found an overall decrease in basal startle response and spontaneous locomotion in offspring born to Poly I:C- compared to saline-treated dams, accompanied by increased microglial density with characteristics of non-reactive activation in the chronic stage of the model. These findings provide additional evidence for a role played by microglial activation in schizophrenia-related pathology in general and psychomotor slowing in particular, and warrant extensive research on the underlying mechanism in order to establish new drug targets for the treatment of schizophrenia patients with an inflammatory component.
authors.affiliation: Experimental Laboratory of Translational Neuroscience and Otolaryngology, University of Antwerp, Campus Drie Eiken, D.T.420, Universiteitsplein 1, 2610 Wilrijk, Belgium.
authors.forename: Karlien
authors.initials: K
authors.lastname: Van den Eynde
authors.forename: Stephan
authors.initials: S
authors.lastname: Missault
authors.forename: Erik
authors.initials: E
authors.lastname: Fransen
authors.forename: Leen
authors.initials: L
authors.lastname: Raeymaekers
authors.forename: Roland
authors.initials: R
authors.lastname: Willems
authors.forename: Wilhelmus
authors.initials: W
authors.lastname: Drinkenburg
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Timmermans
authors.forename: Samir
authors.initials: S
authors.lastname: Kumar-Singh
authors.forename: Stefanie
authors.initials: S
authors.lastname: Dedeurwaerdere
mesh_terms: D000161:Acoustic Stimulation; D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D017628:Microglia / Q000187:drug effects / Q000276:immunology*; D009043:Motor Activity / Q000187:drug effects / Q000276:immunology*; D011070:Poly I-C / Q000494:pharmacology; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000276:immunology* / Q000503:physiopathology; D051381:Rats; D013216:Reflex, Startle / Q000276:immunology; D012559:Schizophrenia / Q000276:immunology* / Q000503:physiopathology
chemical_list: D011070:Poly I-C
keywords: Autism; Locomotion; Maternal immune activation; Neuroinflammation; Poly I:C; Schizophrenia