Alteration of brain volume in IL-6 overexpressing mice related to autism
Abnormal neuroimmune responses have been reported to be associated with autism and could be appropriate targets for pharmacologic intervention. Our previous studies showed that neuroimmune factor, interleukin (IL)-6, was significantly elevated in the fontal cortex and cerebellum of autistic subjects. The IL-6 overexpressing mice displayed several autism-like features as well as an abnormal dendritic spine morphology and synaptic function. The purpose of this study was to examine the volumetric differences in the brain of IL-6 overexpressing mice and compare with corresponding control mice using magnetic resonance imaging. Here we show that IL-6 overexpressing mice display an increase in the total brain volume. In addition, the lateral ventricle is also enlarged in the IL-6 overexpressing mice. The brain structures surrounding the lateral ventricle were squeezed and deformed from the normal location. These results indicate that IL-6 elevation in the brain could mediate neuroanatomical abnormalities. Taking together with our previous findings, a mechanism by which IL-6 may be involved in the pathogenesis of autism is proposed.
Available from: Alexei Verkhratsky
- "More specifically, the clinical onset of autism seems to be related to a reduced head size at birth and a sudden and excessive increase in the size of the head between 1 to 2 months and between 6 to 14 months (Courchesne et al., 2003; Wei et al., 2013). Incidentally, mice with higher levels of IL-6 in the brain show an increase in total brain volume and enlargement of the lateral ventricle (Wei et al., 2012). Neuroanatomical abnormalities seen in ASD patients are consistent with the reported neuroimmune alterations, where cytokines like IL-6, IL-8, TNF-␣, GM-CSF, and IFN-␥ were significantly increased in autistic brains when compared to control samples (Li et al., 2009; Wei et al., 2011). "
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ABSTRACT: The aetiology of autism spectrum disorders remains unclear although a growing number of associated genetic abnormalities and environmental factors have been discovered in recent decades. These advancements coincided with a remarkable increase in the comprehension of physiological functions and pathological potential of neuroglia in the central nervous system that led to a notion of fundamental contribution of glial cells into multiple neuropathologies, including neuropsychiatric and developmental disorders. Growing evidence indicates a role for deregulation of astroglial control over homeostasis and plastic potential of neural networks as well as microglial malfunction and neuroinflammatory response in the brains of autistic patients. In this review, we shall summarize the status and pathological potential of neuroglia and argue for neuroglial roots of autistic disorders.
Neuroscience & Biobehavioral Reviews 11/2013; 38:160-172. DOI:10.1016/j.neubiorev.2013.11.008 · 8.80 Impact Factor
Available from: Andrew J Moorhouse
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ABSTRACT: The traditional role of microglia has been in brain infection and disease, phagocytosing debris and secreting factors to modify disease progression. Recent evidence extends their role to healthy brain homeostasis, including the regulation of cell death, synapse elimination, neurogenesis, and neuronal surveillance. These actions contribute to the maturation and plasticity of neural circuits that ultimately shape behavior. Here we review microglial contributions to the development, plasticity, and maintenance of neural circuits with a focus on interactions with synapses. We introduce this topic by reviewing recent studies on the migration and proliferation of microglia within the brain, and conclude with the proposal that microglia dysfunction may adversely affect brain function, and thereby contribute to the development of psychiatric and neurological disorders.
Trends in Neurosciences 12/2012; 36(4). DOI:10.1016/j.tins.2012.11.007 · 13.56 Impact Factor
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ABSTRACT: Autism spectrum disorder(s) (ASDs) is a neurodevelopmental disorder characterized by stereotyped behaviours and impairments in communication and social interactions. This heterogeneity has been a major obstacle in uncovering the aetiology and biomarkers of ASDs. Rodent models with genetic modifications or environmental insults have been created to study particular endophenotypes and bridge the gap between genetics and behavioural phenotypes. Translational neuroimaging modalities with their ability to screen the brain noninvasively and yield structural, biochemical and functional information provide a unique platform for discovery and evaluation of such endophenotypes in preclinical and clinical research.
We reviewed literature on translational neuroimaging in rodent models of ASDs. The most prominent models will be described and the respective neuroimaging endophenotypes will be discussed with reference to human data. A perspective on future directions of translational neuroimaging in animal models of ASDs will be given.
To date, we experience a proliferation of rodent models which recapitulate specific liabilities identified in ASDs patients. Translational neuroimaging in these models is emerging but is skewed towards magnetic resonance imaging (MRI) modalities. Volumetric and structural assessments of the brain are dominating and a host of endophenotypes have been reported that allude to findings in ASDs patients but with only few to converge among the models. Caveats of current studies are the diverging biological conditions related to genetic background and age of the animals. It is anticipated that longitudinal and functional assessments will gain much importance and will help elucidating mechanistic relationship between behavioural and structural endophenotypes.
Psychopharmacology 07/2013; 231(6). DOI:10.1007/s00213-013-3200-z · 3.88 Impact Factor
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