The neuropathology of autism - neuronal cytoarchitectural alterations and glial cell responses

Schmitz, C. and Rezaie, Payam (2007). The neuropathology of autism - neuronal cytoarchitectural alterations and glial cell responses. In: Autism Research in the UK - from diagnosis to intervention (National Conference), 11-12 May 2007, Milton Keynes, UK.



Structural and pathological abnormalities affecting the brainstem (particularly the olivary nuclei), cerebellum, limbic system (hippocampus and amygdala) and the neocortex have been described to varying degrees in cases of autism examined at post-mortem (Palmen et al. 2004). Evidence for neurodevelopmental disturbances in autism may be further derived from reports of altered brain volume (megalencephaly), cortical dysgenesis and abnormalities in neuronal alignment within the cerebral cortex, as well as cytoarchitectural changes within the amygdala (with fewer neurons particularly in the lateral nucleus), and the cerebellum (loss of Purkinje neurons). Preliminary reports have also suggested that white matter abnormalities, neuroinflammation (Vargas et al. 2005), neuroglial activation (Vargas et al. 2005; Rezaie et al. 2006) and oxidative stress are further components associated with autism. Nevertheless, with the exception of Purkinje cell loss within the cerebellum (which is not in itself a pathological hallmark for autism), the neuropathology of autism still remains largely undefined, with inconsistent findings possibly reflecting (i) interindividual differences (the autism spectrum), (ii) analysis of small sample sizes, (iii) biases in results (co-occurrence of epilepsy, ‘high’ or ‘low’-functioning status, and pathology related to agonal changes pre-mortem), and/or (iv) aetio-pathological differences in the development of the condition (i.e. altered development of a distributed neural network involving a number of brain regions or ‘systems’ rather than localised, neurodevelopmental alterations). For the past few years, we have been investigating aspects of the neuropathology of autism in cohorts of individuals whose brain had been donated for research, to the MRC London Neurodegenerative Diseases Brain Bank at the Institute of Psychiatry in the UK, and the Autism Tissue Program (ATP) in the US. The ATP was established in 1998 to oversee and manage brain donations related to neurological research in autism in the US (Pickett 2001; Pickett and London 2005). Research data from studies utilising these precious resources are integrated into a database – the ATP Informatics Portal (Brimacombe et al. 2007), which enables detailed targeted comparison of neurological and neuroinformatic data to be accessed for each individual case and cross-referenced. Together with other investigators, we are engaged in a collaborative research effort referred to as the ‘ATP Brain Atlas Project’ which attempts to address questions relating to the neuropathology of autism in a defined cohort of cases. Our ongoing collaborative studies have been funded by the National Alliance for Autism Research (NAAR) and are currently funded by Autism Speaks. Our findings in relation to (i) minicolumnar arrangements within the neocortex (Poster 9; Casanova et al. 2006), (ii) neuronal cytoarchitectural alterations within the fusiform gyrus, and (iii) glial cell responses within the cerebral cortex in autism, will be presented at the meeting.

Brimacombe MB et al. (2007) Autism post-mortem neuroinformatic resource: the autism tissue program (ATP) informatics portal. J Autism Dev Disord 37: 574-579.
Casanova MF et al. (2006) Minicolumnar abnormalities in autism. Acta Neuropathol 112: 287-303.
Palmen SJ et al. (2004) Neuropathological findings in autism. Brain 127: 2572-2583.
Pickett J (2001) Current investigations in autism brain tissue research. J Autism Dev Disord 31: 521-527.
Pickett J, London E (2005) The neuropathology of autism: a review. J Neuropathol Exp Neurol 64: 925-935.
Rezaie P et al. (2006) Assessment of glial cell reactivity within the frontal lobe in autism. Neuropathol Appl Neurobiol 32:226-227.
Vargas DL et al. (2005) Neuroglial activation and neuroinflammation in the brain of patients with autism. Ann Neurol 57: 67-81.

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