The Laboratory of Autism Neuroscience Research

Overview

CalbindinCalbindin-Positive Interneuron in the fusiform gyrus, an area associated with object and face recognition. (1000x)

Autism is a developmental neurologic disorder that is characterized by impaired social interaction, delayed and disordered language, abnormal responses to sensory stimuli, and an insistence on sameness in the environment. While the etiology of autism is unknown the disorder is thought to be highly genetic: recent findings in the field have pointed to key genes suspected to be involved in the pathology of the disorder. In the Blatt laboratory for Autism Neuroscience Research, we investigate the role and significance of specific biomarkers as products of these abnormalities in genetic expression. Our focus has been to explore the GABAergic and Glutamatergic systems in parallel, investigating the balance of excitation and inhibition in affected areas of the autistic brain. We study the neuropathology and neuropharmacology of autism in postmortem human brain tissue utilizing modern methods such as in situ hybridization, immunohistochemistry, and in vitro ligand binding for neurotransmitter receptors. Current motor and cognitive regions of interest include the cerebellum, limbic system and cerebral cortex. We have previously demonstrated alterations in the GABAergic system in multiple brain regions, and our studies are now revealing abnormal expression of specific types of serotonergic and glutamatergic receptors. By characterizing abnormalities in the key neurotransmitter systems involved in early brain development, we hope to better understand the formation of aberrant circuitry and developmental timing of the pathology of autism. In doing so, we aim to quantify novel biomarkers of the disorder, thus identifying specific targets for the development of pharmacological therapies for this complex disorder.

3H 

 

Recent Books and Publications

Blatt, G.J., ed., (2010) The Neurochemical Basis of Autism: Molecules to Minicolumns, Springer Publishers, N.Y., Berlin.

Blatt GJ, Fatemi SH. (2011) Alterations in GABAergic biomarkers in the autism brain: research findings and clinical implications. Anat Rec. 294(10):1646-52

Oblak, A., Gibbs T.T. and Blatt,G.J. (2011) Reduced GABAA receptors and benzodiazepine binding sites in the posterior cingulate cortex and fusiform gyrus in autism. Brain Res. 1380:218-228.

Oblak, A., Kemper, T.L., Bauman, M.L. and Blatt, G.J. (2011) Altered posterior cingulate cortical cytoarchitecture, but normal density of neurons and interneurons in the posterior cingulate cortex and fusiform gyrus in autism. Autism Res. 4(3):200-211.

Lawrence, Y.L., Kemper, T.L., Bauman, M.L., and Blatt, G.J.  (2010) Parvalbumin, Calbindin, and Calretinin Immunoreactive Interneuron Density in Autism.  Acta Neurol. Scan. 121(2):99-108.

Oblak, A., Gibbs, T.T., and Blatt, G.J.  (2010) Decreased GABAB receptors in the cingulate cortex and fusiform gyrus in autism. J. Neurochem. 114(5):1414-1423.

Oblak, A, Gibbs, T.T., and Blatt, G.J.  (2009) Decreased GABAA receptors and benzodiazepine binding sites in the anterior cingulate cortex in autism.  Autism Res. 2:205-219.

Yip, J., Soghomonian, J-J. and Blatt, G.J. (2009) Decreased GAD65 mRNA levels in select subpopulations of neurons in the cerebellar dentate nuclei in autism: an in situ hybridization study. Autism Res. 2:50-59.

Yip, J., Soghomonian, J-J. and Blatt, G.J. (2008) Increased GAD67 mRNA expression in cerebellar interneurons in autism:implications for Purkinje cell dysfunction. J. Neurosci. Res. 86:525-530.

Yip, J., Soghomonian, J-J. and Blatt, G.J. (2007)  Decreased GAD67 mRNA levels in cerebellar Purkinje cells in autism: pathophysiological implications. Acta Neuropath. 113:559-568.

Methodology

Purkinje Cell

Purkinje cell in the cerebellum of a control brain, immuno-labeled with Calcium binding protein Calbindin-D28K. (1000x)

The Laboratory of Autism Neuroscience Research utilizes a wide array of methods investigating the neuropathologic and neurochemical basis of autism. Fresh-frozen and fixed tissue sections from individuals with autism and matched controls are used in our studies. Standard Nissl stains are used to stain cytoarchitecture of brain areas. Stereological principles are used for neuronal counts on computer-linked microscopes. Immunocytochemistry is used to label GABAergic and glutamatergic biomarkers on specific cell types and fibers. In situ hybridization is performed in collaboration with our colleague Dr. Jean-Jacques Soghomonian to label mRNA expression of key synthesizing enzymes and receptor subtypes. Ligand binding autoradiography is utilized to label the density and distribution of different types of neurotransmitter uptake sites and receptors.”

People

Blatt Lab photo

Gene J. Blatt, PhD, Professor
Dr. Blatt is the Director of all research projects in the laboratory. He has extensive experience in neuroanatomy of the primate brain. Through his previous work on the olivocerebellar projections and on the primate limbic system, he is able to investigate many brain regions in the autistic brain and approach autism research from a unique perspective.

Caitlin Clancy, Research technician
Ms. Clancy is proficient in immunohistochemistry, receptor binding autoradiography, and is currently using stereological analysis to quantify Purkinje cell densities in the cerebellum, specifically Vermis lobule VI and Crus II. Ms. Clancy is also gaining proficiency in in situ hybridization techniques.

Shiela Kern, Research Technician
Ms. Kern is proficient in immunohistochemistry, receptor binding autoradiography, and is currently using stereological analysis to quantify subpopulations of GABAergic interneurons in autism and controls in the speech and language areas, specifically Wernicke’s and Broca’s Area.

Megan Moretti, Master’s Student (Vesalius Program)
Ms. Moretti is a student in the Department of Anatomy and Neurobiology, and is conducting research in the glutamatergic system in autism, for her master’s thesis.

Natalie Copeland, BU Junior
Ms. Copeland assists with several different lab projects and is gaining proficiency in immunhistochemistry and ligand binding techniques in post mortem autism tissue.

Laboratory of Autism Neuroscience Alumni

Anna Paola Piras, Post Doctorate Research Fellow
Dr. Piras’s project focused on determining abnormalities in mRNA levels in the Glutamate receptor subunits within the cerebellum in autistic post-mortem tissue compared to matched controls. She is an expert in ligand binding, in situ hybridization, and immunohistochemistry techniques.

Adrian Oblak, PhD.
Dr. Oblak’s PhD thesis project examined the neuropathology and neurochemical changes in the cingulate cortex and fusiform gyrus in individuals with autism compared to matched controls. She recently published four journal articles on her findings (See publication list). Dr. Oblak is currently a Post Doctorate Research Fellow in the Department of Anatomy and Neurobiology.

Elizabeth Whitney, PhD.
Dr. Whitney completed her PhD. in the laboratory resulting in the publication of three recent journal articles on cerebellar neurons in the autism brain. She is currently an Assistant Professor in the Department of Anatomy and Neurobiology.

Monika Chitre, BU Senior
Ms. Chitre was a summer intern and conducted her UROP project in our laboratory, in which she utilized immunohistochemistry to investigate the preservation of the Purkinje cells in the cerebellum of individuals with autism.