Comprehensive Analysis of Glial Abnormalities in the Amygdala in Autism

Thursday, May 17, 2012
Sheraton Hall (Sheraton Centre Toronto)
11:00 AM
J. T. Morgan, D. G. Amaral and C. M. Schumann, Psychiatry and Behavioral Sciences, UC Davis M.I.N.D. Institute, Sacramento, CA
Background: The amygdala plays a modulatory role in social and emotional processing, which are core deficits in autism, and has been strongly implicated as structurally and functionally abnormal in the disorder. In a previous postmortem brain tissue study, we reported a reduction in the number of neurons in the amygdala in a cohort of seizure-free, age-matched adolescents and adults with an autism spectrum disorder. Microglia are innate immune effector cells in the brain that when activated carry out an array of functions ranging from phagocytosis of apoptotic neurons to neuroprotection. Increased microglial activation has been found in other brain regions in autism, but microglia have not been assessed in the amygdala. In addition, the other major glial populations, oligodendrocytes, astrocytes, and endothelial cells, have yet to be stereologically assessed for abnormalities in individuals with autism.

Objectives: The primary goal of this study was to comprehensively examine glial cell abnormalities in the amygdala of adolescents and adults with autism. In addition, we wanted to investigate if the reduction in neuron number we previously observed might be related to glial pathology. 

Methods: We carried out a comprehensive stereological study of the number of microglia, oligodendrocytes, astrocytes, and endothelial cells in the same defined regions of the amygdala and in the same cases (n = 8 autism, n = 10 control, ranging in age from 10-44 years of age) as the prior stereological study of neuron number. We also measured microglial cell body size, as somal enlargement is indicative of substantial activation. 

Results: We observed significant increases in both the number of microglia and the proportion of large microglial cell bodies in the autism cases, indicative of increased microglial activation; there was marked heterogeneity in the level of activation among the autism cases. A striking reduction of oligodendrocytes was noted in the subgroup of autism cases with pronounced microglial activation, and reduced oligodendrocyte number was significantly correlated with increased microglial cell body size. However, there was no relationship between the increased microglial activation and the reduction in neuron number previously observed in these autism cases.  

Conclusions: Increased microglial activation is present in the amygdala of some but not all adult and adolescent subjects with autism. The autism subgroup that displays strong microglial activation may also demonstrate reduced oligodendrocyte number. This may reflect oligodendrocyte susceptibility to factors produced by microglial activation or another perturbation that causes both oligodendrocyte loss and microglial activation. These findings may define a distinct phenotype of autism with multiple related glial abnormalities, and confirm the presence of heterogeneity at the cellular level in autism. We found no association between microglial activation and reduced neuron number, suggesting that microglial activation in autism is not strongly associated with neuron loss as would be expected in a classic neurodegenerative profile such as that in Alzheimer's disease. Additional studies are needed to explore if increased microglial activation and its relationship to reduced oligodendrocyte number is present in children with autism or is a phenomenon that occurs later, during adolescence and adulthood.

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