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Perineuronal Nets and Parvalbumin Interneurons in the PolyI:C Model of Schizophrenia Open Access

Descriptions

Other title
Subject/Keyword
Extracellular Matrix
Perineuronal Nets
Schizophrenia
Type of item
Thesis
Degree grantor
University of Alberta
Author or creator
Paylor, John W
Supervisor and department
Winship, Ian R (Psychiatry)
Examining committee member and department
Kerr, Bradley (Neuroscience, Pharmacology)
Dursun, Serdar (Psychiatry)
Fouad, Karim (Neuroscience, Rehabilitation Medicine)
Winship, Ian (Neuroscience, Psychiatry)
Department
Centre for Neuroscience
Specialization

Date accepted
2015-12-24T13:31:44Z
Graduation date
2016-06
Degree
Master of Science
Degree level
Master's
Abstract
Schizophrenia (SCZ) is a psychiatric disorder that, despite a high prevalence (1% population worldwide) and burden of disease (1% global burden of disease), has a poorly understood etiology. While symptoms of SCZ typically manifest during adolescence and early adulthood, there is a substantial body of research linking prenatal events (e.g. early infection) to one’s risk for developing SCZ. Human post-mortem analyses have suggested perineuronal nets (PNNs) as a potential biomarker for SCZ, as PNNs are deficient in a number of disease-specific regions of SCZ patients. PNNs, which surround parvalbumin positive (PV) inhibitory interneurons, typically mature during late adolescence and early adulthood when SCZ symptoms often first present. As such, I sought to examine whether a developmental PNN deficit is present in a maternal immune activation model of SCZ in rats. Long-Evans rat dams were treated at gestational day 15 with polyriboinosinic-polyribocytidilic acid (PolyI:C) to induce a strong maternal immune response. The litters were carried to birth and offspring allowed to develop to postnatal days 7 (PND7), 21, 35, and 90. I used histochemistry to assess PNNs, staining with the lectin Wisteria Floribunda Agglutinin, and examined their integrity using epifluorescent and confocal microscopy across a number of brain regions: frontal association cortex, prelimbic cortex, reticular thalamic nucleus, primary auditory cortex, amygdala, and the dorsal and ventral hippocampus. Additionally, I stained for microglia (anti-IBA1) and astrocytes (GFAP) as well as PV interneurons (anti-PV) to assess immune activation and PV neuronal integrity respectively. Consistent with previous research, I find that PNNs increase throughout postnatal development in all regions examined. During adolescence a deficit emerged in the number of PNNs in both the frontal association cortex and medial prelimbic cortex of PolyI:C treated animals. I did not however replicate previous human studies showing PNN associated dysfunction in the primary auditory cortex or amygdala. My examination of PV+ interneurons also showed developmental effects of reduced PV+ interneurons within the basolateral amygdala and a trend towards a reduction in the frontal association cortex. I found that there were no differences in microglial cell density and only minor changes to GFAP immunoreactivity, neither of which were associated with the PNN deficits in the prefrontal cortex. Remarkably, this study shows that a prenatal immune challenge event can result in deficits in PNNs that are not apparent until much later in development during adulthood. Furthermore, my results add to the list of shared pathological features between the PolyI:C model and SCZ itself, as PNNs are disturbed in the prefrontal cortex in both. PNNs along with PV+ interneurons are important regulators of critical windows of heightened plasticity during development. A deficit in PNNs could lead to a permanent pathological upregulation of structural plasticity into adulthood, as well as PV interneuron and cortical inhibitory network dysfunction. These deficits may contribute to a number of behavioural symptoms that appear within the same developmental periods, many of which are associated with the prefrontal cortex.
Language
English
DOI
doi:10.7939/R3F18SP36
Rights
This thesis is made available by the University of Alberta Libraries with permission of the copyright owner solely for the purpose of private, scholarly or scientific research. This thesis, or any portion thereof, may not otherwise be copied or reproduced without the written consent of the copyright owner, except to the extent permitted by Canadian copyright law.
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