Microglia , the brain and Autism – Immune System Connections.

Microglia in the Cerebral Cortex in Autism

http://link.springer.com/article/10.1007/s10803-012-1513-0/fulltext.html

Division of Biology, California Institute of Technology

Comprehensive Autism Center

Abstract

We immunocytochemically identified microglia in fronto-insular (FI) and visual cortex (VC) in autopsy brains of well-phenotyped subjects with autism and matched controls, and stereologically quantified the microglial densities.

Densities were determined blind to phenotype using an optical fractionator probe. In FI, individuals with autism had significantly more microglia compared to controls (p = 0.02). One such subject had a microglial density in FI within the control range and was also an outlier behaviorally with respect to other subjects with autism.

In VC, microglial densities were also significantly greater in individuals with autism versus controls (p = 0.0002).

Since we observed increased densities of microglia in two functionally and anatomically disparate cortical areas, we suggest that these immune cells are probably denser throughout cerebral cortex in brains of people with autism.

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From full paper

“We observed increased densities of microglia in two disparate cortical areas. One possibility is that these increased densities reflect abnormalities specific to these particular cortical areas, since there is evidence that each is involved in autism, or alternatively these results may reflect a widespread difference that occurs throughout the cortex or even much of the brain. Consistent with the possibility that the effect is pan-cortical, Morgan et al. (2010) reported an increase in microglia in subjects with autism in dorsal lateral prefrontal cortex (dlPFC) compared to controls, and found an increase in somal size in microglia in subjects with autism in grey and white matter.”

How and when does the increased density of autistic microglial arrays arise, and how is it maintained? Of course we have no data prior to the time of death, but the consistency of results among 10 subjects with autism of differing ages argues that people with autism have developed a remarkably stable steady-state microglial density.”

“It seems possible that some persistent stimulus is the cause of this sustained higher level of microglial density in the subjects with autism.”

“There is evidence that maternal viral infection in the first trimester and bacterial infection in the second trimester are correlated with an increase in offspring reported to have autism (Atladóttir et al. 2010).”

“Voineagu et al. (2011) conclude that the enriched gene expression of immune and microglial genes observed in their study has a non-genetic etiology and may reflect internal or external environmental influences, which suggests the possibility that the sustained higher levels of microglia density in people with autism may also be environmentally mediated.”

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There is a lot more information to be garnered from a detailed look at the full paper.

I’m sure this paper that builds upon the work of Vargas et al will attract quite a degree of interest in the autism community.

 

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2 Responses to Microglia , the brain and Autism – Immune System Connections.

  1. Hi ASD Research Initiative –

    Indeed, we are quickly leaving behind the time when we continue to ask ‘are there different numbers of microglia in the autism population?’, and instead begin to ask, ‘why are there different numbers of microglia in the autism population?’.

    A ‘persistent stimulus’ as a possible mechanism is one that I like quite a bit, as we have gradually replaced infection with inflammation as a population, though this is a dangerous notion towards the idea of a static rate of autism. The fact that the colonization of microglia from the periphery into the different parts of the brain appears to occur postnatally is a finding that I’m sure is going to be a big hit soon enough; the skeptics are going to have fun getting around that one.

    On a related note, this landed in my inbox this week:

    Distribution of microglia in the postnatal murine nigrostriatal system

    We clearly show that the microglia numbers in the SN and in the striatum dramatically increase from P0 to P15 and significantly decrease in both areas in 18-month-old and 24-month-old animals.

    It seems to be different from region to region, and as always, the jump from rodent to human is fraught with the peril of assumptions, but there are other studies with similar findings.

    – pD

  2. Thanks pD for your comments. 2012 is a tipping point year in ASD research. So many converging lines of research point to the immune system , systemic inflammation and the role of pathogens as major players in autism. Perhaps the most telling evidence setting aside Paul Patterson’s remarkable “mouse” and the one most fresh in my mind is the genetic evidence from Saxena et al. Summed up in this comment below …

    “Others have talked about immune function contributions to autism, but in our study immune involvement has been identified through a completely nonbiased approach,” says Vishal Saxena, PhD, of the Massachusetts General Hospital (MGH) Department of Neurology, first, corresponding and co-senior author of the PLOS ONE paper. “We let the data tell us what was most important; and most tellingly, viral infection pathways were most important in this immune-related mechanism behind autism.”

    https://asdresearchinitiative.wordpress.com/2012/12/08/autism-its-the-immune-system-genetic-pathways-confirmation/

    Cheers and all the best to you and your family over the holiday season. See you in 2013.

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