Office for People With Developmental Disabilities

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Morphometry Laboratory

07/11/12

Jerzy Wegiel, VMD, PhD, Head

[email protected]

The first group of projects of the Morphometry Laboratory is focused on the detection of markers of mechanistic overlap leading to autistic behavior, intellectual deficits, and epilepsy in different neurodevelopmental disorders. The overall goal is to identify the core pathology common for different disorders and targets for treatment alleviating the clinical phenotype regardless of disorder etiology. This concept is supported by complex studies of the pattern of global encephalopathy in autism of unknown origin and autism caused by mutations, including duplication of chromosome 15 and Fragile X syndrome. One study revealed similarities of global and brain region–specific patterns of abnormal neuronal growth, developmental defects of the corpus callosum, and severe deficits of long-distance axonal connections in idiopathic and syndromic autism. Moreover, a deficit of fragile X mental retardation protein 1 (FMRP1) associated with a reduced size of neurons in idiopathic and syndromic autism revealed a mechanistic overlap with Fragile X syndrome.  

Our study of neurologically intact aging subjects identified an index of age-associated neuronal loss up to 40%, which corresponds to a loss of the neuronal reserve without a significant loss of function. The second cluster of projects is concentrated on estimation of the reduction of neuronal reserve in subjects with intellectual deficits caused by trisomy 21 and diagnosed with Down syndrome, a statistical model of further reduction of the number of neurons during accelerated aging in 30- to 40-year-old subjects with Down syndrome, and the rate of neuronal loss due to early onset of beta amyloidosis and neurofibrillary degeneration. These statistical models will identify different targets for treatment in different age groups of individuals with Down syndrome.   

The third cluster of projects is focused on brain inflammation with activated microglial cells in autism and Down syndrome. The first goal is to determine the type and topography of microglial cell infiltration in autism, and their impact on neurons and the contribution to clinical autism phenotype. The second goal is to define a Down syndrome–specific pattern of microglial cell infiltration and the contribution of this process to functional deterioration in the third decade of life and dementia in 40- to 50-year-old subjects with Down syndrome. Parallel studies of the human brain and tg mice are focused on testing the hypothesis that reduction of microglial infiltration reduces neurodegeneration and improves synaptic connections and function.