Age-dependent decrease of GAD65/67 mRNAs but normal densities of GABAergic interneurons in the brain regions of Shank3-overexpressing manic mouse model

Bokyoung Lee, Yinhua Zhang, Yoonhee Kim, Shinhyun Kim, Yeunkum Lee, Kihoon Han

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Dysfunction of inhibitory GABAergic interneurons is considered a major pathophysiological feature of various neurodevelopmental and neuropsychiatric disorders. The variants of SHANK3 gene, encoding a core scaffold protein of the excitatory postsynapse, have been associated with numerous brain disorders. It has been suggested that abnormalities of GABAergic interneurons could contribute to the SHANK3-related disorders, but the limitation of these studies is that they used mainly Shank3 knock-out mice. Notably, Shank3-overexpressing transgenic mice, modeling human hyperkinetic disorders, also show reduced inhibitory synaptic transmission, abnormal electroencephalography, and spontaneous seizures. However, it has not been investigated whether these phenotypes of Shank3 transgenic mice are associated with GABAergic interneuron dysfunction, or solely due to the cell-autonomous postsynaptic changes of principal neurons. To address this issue, we investigated the densities of parvalbumin- and somatostatin-positive interneurons, and the mRNA and protein levels of GAD65/67 GABA-synthesizing enzymes in the medial prefrontal cortex, striatum, and hippocampus of adult Shank3 transgenic mice. We found no significant difference in the measurements performed on wild-type versus Shank3 transgenic mice, except for the decreased GAD65 or GAD67 mRNAs in these brain regions. Interestingly, only GAD65 mRNA was decreased in the hippocampus, but not mPFC and striatum, of juvenile Shank3 transgenic mice which, unlike the adult mice, did not show behavioral hyperactivity. Together, our results suggest age-dependent decrease of GAD65/67 mRNAs but normal densities of certain GABAergic interneurons in the Shank3 transgenic mice.

Original languageEnglish
Pages (from-to)48-54
Number of pages7
JournalNeuroscience Letters
Volume649
DOIs
Publication statusPublished - 2017 May 10

Fingerprint

Interneurons
Transgenic Mice
Messenger RNA
Brain
Hippocampus
Parvalbumins
Brain Diseases
Somatostatin
Prefrontal Cortex
Knockout Mice
Synaptic Transmission
gamma-Aminobutyric Acid
Electroencephalography
Seizures
Proteins
Phenotype
Neurons
Enzymes
Genes

Keywords

  • GABAergic interneuron
  • GAD65
  • GAD67
  • Parvalbumin
  • Shank3

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Age-dependent decrease of GAD65/67 mRNAs but normal densities of GABAergic interneurons in the brain regions of Shank3-overexpressing manic mouse model. / Lee, Bokyoung; Zhang, Yinhua; Kim, Yoonhee; Kim, Shinhyun; Lee, Yeunkum; Han, Kihoon.

In: Neuroscience Letters, Vol. 649, 10.05.2017, p. 48-54.

Research output: Contribution to journalArticle

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