Perineuronal Nets in the Prefrontal Cortex of a Schizophrenia Mouse Model: Assessment of Neuroanatomical, Electrophysiological, and Behavioral Contributions.
Perineuronal Nets in the Prefrontal Cortex of a Schizophrenia Mouse Model: Assessment of Neuroanatomical, Electrophysiological, and Behavioral Contributions.
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DOI：
10.3390/ijms222011140
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发表时间：
2021-10-15
影响因子：
5.6
通讯作者：
Lee CC
中科院分区：
文献类型：
--
作者：
Sultana R;Brooks CB;Shrestha A;Ogundele OM;Lee CC
精神分裂症是一种神经发育障碍，其发病机制包括细胞和细胞外结构的变化。精神分裂症患者与前额叶皮层（PFC）中小清蛋白阳性中间神经元（PV）相关的神经元周围网络（PNNs）失调。然而，这些结构的出生后发育沿着与其相关的神经元在PFC是未探索的，因为是他们的行为和神经活动的影响。因此，在这项研究中，我们采用了DISC 1（分裂症的破坏）突变的精神分裂症小鼠模型，以评估这些发展变化，并测试是否酶消化PNNs在PFC影响精神分裂症样行为和神经活动。在发育过程中，我们发现PNNs、PV的正常形成以及这两个在PFC中的共定位在PND 22（出生后第22天）左右达到峰值。然而，在DISC 1中，突变动物从PND 0至PND 60，PNN和PV均显著降低。在成年动物中用软骨素酶酶消化PNN后，对照动物的行为模式模仿DISC 1突变动物的行为模式，表现出社交性降低、新奇和超声发声增加，而其他行为几乎没有变化，比如工作记忆（Y-迷宫任务涉及内侧颞叶）或抑郁样行为（尾悬挂试验涉及通过下丘脑垂体肾上腺（HPA）轴的处理）。此外，软骨素酶治疗后，PFC的电生理记录显示自发性，高频放电神经元的比例减少，不规则放电神经元的比例增加，与对照组动物的棘波计数增加和棘波间隔减少。这些结果支持的命题，PNNs和PV的异常发展影响PFC的正常神经操作，并有助于精神分裂症DISC 1突变模型中观察到的一些行为表型的出现。
Schizophrenia is a neurodevelopmental disorder whose etiopathogenesis includes changes in cellular as well as extracellular structures. Perineuronal nets (PNNs) associated with parvalbumin-positive interneurons (PVs) in the prefrontal cortex (PFC) are dysregulated in schizophrenia. However, the postnatal development of these structures along with their associated neurons in the PFC is unexplored, as is their effects on behavior and neural activity. Therefore, in this study, we employed a DISC1 (Disruption in Schizophrenia) mutation mouse model of schizophrenia to assess these developmental changes and tested whether enzymatic digestion of PNNs in the PFC affected schizophrenia-like behaviors and neural activity. Developmentally, we found that the normal formation of PNNs, PVs, and colocalization of these two in the PFC, peaked around PND 22 (postnatal day 22). However, in DISC1, mutation animals from PND 0 to PND 60, both PNNs and PVs were significantly reduced. After enzymatic digestion of PNNs with chondroitinase in adult animals, the behavioral pattern of control animals mimicked that of DISC1 mutation animals, exhibiting reduced sociability, novelty and increased ultrasonic vocalizations, while there was very little change in other behaviors, such as working memory (Y-maze task involving medial temporal lobe) or depression-like behavior (tail-suspension test involving processing via the hypothalamic pituitary adrenal (HPA) axis). Moreover, following chondroitinase treatment, electrophysiological recordings from the PFC exhibited a reduced proportion of spontaneous, high-frequency firing neurons, and an increased proportion of irregularly firing neurons, with increased spike count and reduced inter-spike intervals in control animals. These results support the proposition that the aberrant development of PNNs and PVs affects normal neural operations in the PFC and contributes to the emergence of some of the behavioral phenotypes observed in the DISC1 mutation model of schizophrenia.
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影响因子：
3.3
作者：
Fader SM;Imaizumi K;Yanagawa Y;Lee CC
通讯作者：
Lee CC
影响因子：
16.2
作者：
Atallah BV;Bruns W;Carandini M;Scanziani M
通讯作者：
Scanziani M
成人神经系统的塑性和疾病中的信号素。
影响因子：
3.7
作者：
Carulli D;de Winter F;Verhaagen J
通讯作者：
Verhaagen J
影响因子：
3.8
作者：
Bicks LK;Koike H;Akbarian S;Morishita H
通讯作者：
Morishita H
影响因子：
16.2
作者：
Amilhon, Benedicte;Huh, Carey Y. L.;Williams, Sylvain
通讯作者：
Williams, Sylvain