Abstract:
GABAergic interneurons and perineuronal nets (PNNs) are important regulators of plasticity throughout life and their dysfunction has been implicated in the pathogenesis of several neuropsychiatric conditions, including autism spectrum disorders (ASD). PNNs are condensed portions of the extracellular matrix (ECM) that are crucial for neural development and proper formation of synaptic connections. We previously showed a reduced expression of GABAergic interneuron markers in the hippocampus and somatosensory cortex of adult mice lacking the Engrailed2 gene (En2-/- mice), a mouse model of ASD. Since alterations in PNNs have been proposed as a possible pathogenic mechanism in ASD, we hypothesized that the PNN dysfunction may contribute to the neural and behavioral abnormalities of En2-/- mice. Here, we show an increase in the PNN fluorescence intensity, evaluated by Wisteria floribunda agglutinin, in brain regions involved in social behavior and somatosensory processing. In addition, we found that En2-/- mice exhibit altered texture discrimination through whiskers and display a marked decrease in the preference for social novelty. Our results raise the possibility that altered expression of PNNs, together with defects of GABAergic interneurons, might contribute to the pathogenesis of social and sensory behavioral abnormalities.
摘要:
GABA能中间神经元和神经神经网(PNN)是整个生命可塑性的重要调节因子,它们的功能障碍与几种神经精神疾病的发病机理有关。包括自闭症谱系障碍(ASD)。PNN是细胞外基质(ECM)的浓缩部分,对于神经发育和突触连接的正确形成至关重要。我们先前显示缺乏Engrailed2基因的成年小鼠(En2-/-小鼠)的海马和体感皮层中GABA能中间神经元标记物的表达降低,ASD的小鼠模型。由于PNN的改变已被提出作为ASD的可能致病机制,我们假设PNN功能障碍可能导致En2-/-小鼠的神经和行为异常。这里,我们显示了PNN荧光强度的增加,由紫藤凝集素评估,涉及社会行为和体感加工的大脑区域。此外,我们发现En2-/-小鼠通过胡须表现出改变的质地辨别能力,并且对社会新颖性的偏好显着下降。我们的结果提高了PNN表达改变的可能性,连同GABA能中间神经元的缺陷,可能有助于社会和感觉行为异常的发病机制。