Increased GAD67 mRNA expression in cerebellar interneurons in autism: Implications for Purkinje cell dysfunction.

Increased GAD67 mRNA expression in cerebellar interneurons in autism: Implications for Purkinje cell dysfunction. Research Abstract Details 

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Increased GAD67 mRNA expression in cerebellar interneurons in autism: Implications for Purkinje cell dysfunction. Abstract Text:

Jane Yip,Jean-Jacques Soghomonian,Gene J Blatt,Jane Yip,Jean-Jacques Soghomonian,Gene J Blatt,

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. (c) 2007 Wiley-Liss, Inc.

Increased GAD67 mRNA expression in cerebellar interneurons in autism: Implications for Purkinje cell dysfunction. Publishing Authors By Initials

J Yip,JJ Soghomonian,GJ Blatt,J Yip,JJ Soghomonian,GJ Blatt,

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Increased GAD67 mRNA expression in cerebellar interneurons in autism: Implications for Purkinje cell dysfunction. Journal Published:

PUBLICATION TYPE: Journal Article

Journal: Journal of neuroscience research

VOLUME: 86

Page Numbers: 525-30

Journal Abbreviation: J. Neurosci. Res.

ISSN: 0360-4012

DAY: 15

MONTH: Feb

YEAR: 2008

Increased GAD67 mRNA expression in cerebellar interneurons in autism: Implications for Purkinje cell dysfunction. Information

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LANGUAGE: eng

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Grant and Affiliation Information for Increased GAD67 mRNA expression in cerebellar interneurons in autism: Implications for Purkinje cell dysfunction.

AFFILIATION: Department of Anatomy and Neurobiology, Boston University School of Medicine, Boston, Massachusetts.

Country: United States

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MEDLINETA: J Neurosci Res

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