Altered Expression of GABAergic Markers in the Forebrain of Young and Adult <i>Engrailed-2</i> Knockout Mice

• Main Authors: Giovanni Provenzano, Angela Gilardoni, Marika Maggia, Mattia Pernigo, Paola Sgadò, Simona Casarosa, Yuri Bozzi
• Format: Article
• Language: English
• Published: MDPI AG 2020-04-01
• Series: Genes
• Subjects: interneuron; parvalbumin; somatostatin; GABA; receptor; hippocampus
• Online Access: https://www.mdpi.com/2073-4425/11/4/384

Impaired function of GABAergic interneurons, and the subsequent alteration of excitation/inhibition balance, is thought to contribute to autism spectrum disorders (ASD). Altered numbers of GABAergic interneurons and reduced expression of GABA receptors has been detected in the brain of ASD subjects and mouse models of ASD. We previously showed a reduced expression of GABAergic interneuron markers parvalbumin (PV) and somatostatin (SST) in the forebrain of adult mice lacking the <i>Engrailed2</i> gene (<i>En2</i>^-/- mice). Here, we extended this analysis to postnatal day (P) 30 by using in situ hybridization, immunohistochemistry, and quantitative RT-PCR to study the expression of GABAergic interneuron markers in the hippocampus and somatosensory cortex of <i>En2</i>^-/- and wild type (WT) mice. In addition, GABA receptor subunit mRNA expression was investigated by quantitative RT-PCR in the same brain regions of P30 and adult <i>En2</i>^-/- and WT mice. As observed in adult animals, PV and SST expression was decreased in <i>En2</i>^-/- forebrain of P30 mice. The expression of GABA receptor subunits (including the ASD-relevant <i>Gabrb3</i>) was also altered in young and adult <i>En2</i>^-/- forebrain. Our results suggest that GABAergic neurotransmission deficits are already evident at P30, confirming that neurodevelopmental defects of GABAergic interneurons occur in the <i>En2</i> mouse model of ASD.