Format

Send to

Choose Destination
See comment in PubMed Commons below
J Cent Nerv Syst Dis. 2014 Apr 7;6:21-8. doi: 10.4137/JCNSD.S14012. eCollection 2014.

Temporal- and Location-Specific Alterations of the GABA Recycling System in Mecp2 KO Mouse Brains.

Author information

1
Neuroscience Laboratory, Hugo Moser Research Institute at Kennedy Krieger.
2
Neuroscience Laboratory, Hugo Moser Research Institute at Kennedy Krieger. ; Departments of Neurology, Johns Hopkins University School of Medicine; Baltimore, USA. ; Department of Pediatrics, Johns Hopkins University School of Medicine; Baltimore, USA.
3
Neuroscience Laboratory, Hugo Moser Research Institute at Kennedy Krieger. ; Departments of Neurology, Johns Hopkins University School of Medicine; Baltimore, USA.

Abstract

Rett syndrome (RTT), associated with mutations in methyl-CpG-binding protein 2 (Mecp2), is linked to diverse neurological symptoms such as seizures, motor disabilities, and cognitive impairments. An altered GABAergic system has been proposed as one of many underlying pathologies of progressive neurodegeneration in several RTT studies. This study for the first time investigated the temporal- and location-specific alterations in the expression of γ-amino butyric acid (GABA) transporter 1 (GAT-1), vesicular GABA transporter (vGAT), and glutamic acid decarboxylase 67kD (GAD67) in wild type (WT) and knockout (KO) mice in the Mecp2(tm1.1Bird/y) mouse model of RTT. Immunohistochemistry (IHC) co-labeling of GAT-1 with vGAT identified GABAergic synapses that were quantitated for mid-sagittal sections in the frontal cortex (FC), hippocampal dentate gyrus (DG), and striatum (Str). An age-dependent increase in the expression of synaptic GABA transporters, GAT-1, and vGAT, was observed in the FC and DG in WT brains. Mecp2 KO mice showed a significant alteration in this temporal profile that was location-specific, only in the FC. GAD67-positive cell densities also showed an age-dependent increase in the FC, but a decrease in the DG in WT mice. However, these densities were not significantly altered in the KO mice in the regions examined in this study. Therefore, the significant location-specific downregulation of synaptic GABA transporters in Mecp2 KO brains with unaltered densities of GAD67-positive interneurons may highlight the location-specific synaptic pathophysiology in this model of RTT.

KEYWORDS:

GABAergic neurons; GAT-1; MeCP2 mutation; Rett syndrome; lipofuscin; synapse

PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Libertas Academica Icon for PubMed Central
    Loading ...
    Support Center