Alterations of GABAergic Neuron-Associated Extracellular Matrix and Synaptic Responses in Gad1 -Heterozygous Mice Subjected to Prenatal Stress

Frontiers in Cellular Neuroscience
Tianying WangAtsuo Fukuda

Abstract

Exposure to prenatal stress (PS) and mutations in Gad1, which encodes GABA synthesizing enzyme glutamate decarboxylase (GAD) 67, are the primary risk factors for psychiatric disorders associated with abnormalities in parvalbumin (PV)-positive GABAergic interneurons in the medial prefrontal cortex (mPFC). Decreased expression of extracellular matrix (ECM) glycoproteins has also been reported in patients with these disorders, raising the possibility that ECM abnormalities may play a role in their pathogenesis. To elucidate pathophysiological changes in ECM induced by the gene-environment interaction, we examined heterozygous GAD67-GFP (Knock-In KI; GAD67+/GFP) mice subjected to PS from embryonic day 15.0 to 17.5. Consistent with our previous study, we confirmed a decrease in the density of PV neurons in the mPFC of postnatal GAD67+/GFP mice with PS, which was concurrent with a decrease in density of PV neurons surrounded by perineuronal nets (PNNs), a specialized ECM important for the maturation, synaptic stabilization and plasticity of PV neurons. Glycosylation of α-dystroglycan (α-DG) and its putative mediator fukutin (Fktn) in the ECM around inhibitory synapses has also been suggested to contribute to disease development. We f...Continue Reading

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Citations

Apr 18, 2020·Pflügers Archiv : European journal of physiology·Tenpei Akita, Atsuo Fukuda
Apr 9, 2020·Frontiers in Cellular Neuroscience·Jinting GuanGuoli Ji
Jul 21, 2020·Neuroscience and Biobehavioral Reviews·Sabine SpijkerDanai Riga
Apr 28, 2021·Progress in Neurobiology·Navneet A Vasistha, Konstantin Khodosevich

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Methods Mentioned

BETA
glycosylation
transgenic
PCR

Software Mentioned

BLAST
Imaris
Primer

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