CaltechTHESIS
  A Caltech Library Service

Microglia in the Cerebral and Cerebellar Cortices in Individuals with Autism

Citation

Tetreault, Nicole Anne (2013) Microglia in the Cerebral and Cerebellar Cortices in Individuals with Autism. Dissertation (Ph.D.), California Institute of Technology. doi:10.7907/VGPA-4D87. https://resolver.caltech.edu/CaltechTHESIS:06072013-005232013

Abstract

In this thesis, we explore the density of the microglia in the cerebral and cerebellar cortices of individuals with autism to investigate the hypothesis that neuroinflammation is involved in autism. We describe in our findings an increase in microglial density in two disparate cortical regions, frontal insular cortex and visual cortex, in individuals with autism (Tetreault et al., 2012). Our results imply that there is a global increase in the microglial density and neuroinflammation in the cerebral cortex of individuals with autism.

We expanded our cerebellar study to additional neurodevelopmental disorders that exhibit similar behaviors to autism spectrum disorder and have known cerebellar pathology. We subsequently found a more than threefold increase in the microglial density specific to the molecular layer of the cerebellum, which is the region of the Purkinje and parallel fiber synapses, in individuals with autism and Rett syndrome. Moreover, we report that not only is there an increase in microglia density in the molecular layer, the microglial cell bodies are significantly larger in perimeter and area in individuals with autism spectrum disorder and Rett syndrome compared to controls that implies that the microglia are activated. Additionally, an individual with Angelman syndrome and the sibling of an individual with autism have microglial densities similar to the individuals with autism and Rett syndrome. By contrast, an individual with Joubert syndrome, which is a developmental hypoplasia of the cerebellar vermis, had a normal density of microglia, indicating the specific pathology in the cerebellum does not necessarily result in increased microglial densities. We found a significant decrease in Purkinje cells specific to the cerebellar vermis in individuals with autism.

These findings indicate the importance for investigation of the Purkinje synapses in autism and that the relationship between the microglia and the synapses is of great utility in understanding the pathology in autism. Together, these data provide further evidence for the neuroinflammation hypothesis in autism and a basis for future investigation of neuroinflammation in autism. In particular, investigating the function of microglia in modifying synaptic connectivity in the cerebellum may provide key insights into developing therapeutics in autism spectrum disorder.

Item Type:Thesis (Dissertation (Ph.D.))
Subject Keywords:autism, microglia, neuroinflammation, cerebral cortex, fronto-insular cortex, visual cortex, Purkinje cells, cerebellum, Angelman syndrome, Joubert syndrome, Rett syndrome
Degree Grantor:California Institute of Technology
Division:Biology
Major Option:Biology
Thesis Availability:Public (worldwide access)
Research Advisor(s):
  • Allman, John Morgan (advisor)
  • Wold, Barbara J. (co-advisor)
Thesis Committee:
  • Adolphs, Ralph (chair)
  • Wold, Barbara J.
  • Patterson, Paul H.
  • Allman, John Morgan
Defense Date:23 May 2013
Funders:
Funding AgencyGrant Number
NIHMH089406
Simons FoundationSFARI #137661
James S. McDonnell FoundationUNSPECIFIED
College Women's Club of PasadenaUNSPECIFIED
Kanal FoundationUNSPECIFIED
Caltech SURF programUNSPECIFIED
Record Number:CaltechTHESIS:006072013-005232013
Persistent URL:https://resolver.caltech.edu/CaltechTHESIS:06072013-005232013
DOI:10.7907/VGPA-4D87
Related URLs:
URLURL TypeDescription
http://link.springer.com/article/10.1007/s10803-012-1513-0DOIUNSPECIFIED
Default Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:7876
Collection:CaltechTHESIS
Deposited By: Nicole Tetreault
Deposited On:08 May 2015 16:03
Last Modified:04 Oct 2019 00:02

Thesis Files

[img]
Preview
PDF - Final Version
See Usage Policy.

79MB

Repository Staff Only: item control page