Document Detail


Increased GAD67 mRNA expression in cerebellar interneurons in autism: implications for Purkinje cell dysfunction.
MedLine Citation:
PMID:  17918742     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
It has been widely reported that in autism, the number of Purkinje cells (PCs) is decreased, and recently, decreased expression of glutamic acid decarboxylase 67 (GAD67) mRNA in Purkinje cells also has been observed. However, the autism literature has not addressed key GABAergic inputs into Purkinje cells. Inhibitory basket and stellate cell interneurons in the molecular layer of the cerebellar cortex provide direct key GABAergic input into Purkinje cells and could potently influence the output of Purkinje cells to deep cerebellar nuclei. We investigated the capacity for interneuronal synthesis of gamma-amino butyric acid (GABA) in both types of interneurons that innervate the remaining PCs in the posterolateral cerebellar hemisphere in autism. The level of GAD67 mRNA, one of the isoforms of the key synthesizing enzymes for GABA, was quantified at the single-cell level using in situ hybridization in brains of autistic and aged-matched controls. The National Institutes of Health imaging system showed that expression of GAD67 mRNA in basket cells was significantly up-regulated, by 28%, in eight autistic brains compared with that in eight control brains (mean +/- SEM pixels per cell, 1.03 +/- 0.05 versus 0.69 +/- 0.05, respectively; P < 0.0001 by independent t test). Stellate cells showed a trend toward a small increase in GAD67 mRNA levels, but this did not reach significance. The results suggest that basket cells likely provide increased GABAergic feed-forward inhibition to PCs in autism, directly affecting PC output to target neurons in the dentate nucleus and potentially disrupting its modulatory role in key motor and/or cognitive behaviors in autistic individuals.
Authors:
Jane Yip; Jean-Jacques Soghomonian; Gene J Blatt
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural    
Journal Detail:
Title:  Journal of neuroscience research     Volume:  86     ISSN:  1097-4547     ISO Abbreviation:  J. Neurosci. Res.     Publication Date:  2008 Feb 
Date Detail:
Created Date:  2008-01-28     Completed Date:  2008-04-28     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7600111     Medline TA:  J Neurosci Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  525-30     Citation Subset:  IM    
Copyright Information:
(c) 2007 Wiley-Liss, Inc.
Affiliation:
Department of Anatomy and Neurobiology, Boston University School of Medicine, Boston, Massachusetts 02118, USA. jyip@bu.edu
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MeSH Terms
Descriptor/Qualifier:
Autistic Disorder / metabolism*,  pathology,  physiopathology
Brain / metabolism,  pathology
Cerebellar Cortex / metabolism*
Glutamate Decarboxylase / genetics*
Humans
In Situ Hybridization
Interneurons / metabolism
Neurons / metabolism*
Purkinje Cells
RNA, Messenger / metabolism*
Tissue Distribution
Up-Regulation
gamma-Aminobutyric Acid / biosynthesis
Grant Support
ID/Acronym/Agency:
HD39459-04/HD/NICHD NIH HHS
Chemical
Reg. No./Substance:
0/RNA, Messenger; 56-12-2/gamma-Aminobutyric Acid; EC 4.1.1.15/Glutamate Decarboxylase; EC 4.1.1.15/glutamate decarboxylase 1

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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