Down syndrome (DS) is the most common genetic cause of intellectual disability but the neuroanatomical abnormalities that contribute to specific cognitive deficits in individuals with DS have not been well defined. Histopathological observations, though limited, have consistently implicated reduced neuron number as a major defect in the DS cerebral cortex. Yet the identity of the neuron subtype that is affected is not known and this lack of information lessens both our knowledge of DS neuropathology and our ability to define potential therapies. It is therefore critical to our understanding of the neurobiological basis of intellectual disability in DS to define the neurons that are reduced in DS cerebral cortex. This small self-contained proposal aims to test the simple hypothesis that there are fewer interneurons in human DS cortex. Inhibitory interneurons will be identified and counted in post-mortem DS human brain and compared to controls using modern techniques for immunostaining and quantification.

Public Health Relevance

As the most common genetic cause of intellectual disability, Down syndrome is a public health concern. The proposed research aims to define the basis for neuroanatomical differences in Down syndrome brain. Specifically, the aim of the research is to identify which neurons are lacking in the human post-mortem Down syndrome brain.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Small Research Grants (R03)
Project #
1R03HD083538-01A1
Application #
9034147
Study Section
Biobehavioral and Behavioral Sciences Subcommittee (CHHD)
Program Officer
Parisi, Melissa
Project Start
2015-12-01
Project End
2017-11-30
Budget Start
2015-12-01
Budget End
2016-11-30
Support Year
1
Fiscal Year
2016
Total Cost
Indirect Cost
Name
University of Wisconsin Madison
Department
Pediatrics
Type
Graduate Schools
DUNS #
161202122
City
Madison
State
WI
Country
United States
Zip Code
53715