Integrin β1/FAK/SRC signal pathway is involved in autism spectrum disorder in Tspan7 knockout rats.
Integrin β1/FAK/SRC signal pathway is involved in autism spectrum disorder in Tspan7 knockout rats.
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整合素β1/FAK/SRC信号通路参与Tspan7敲除大鼠自闭症谱系障碍
DOI：
10.26508/lsa.202201616
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发表时间：
2023-03
影响因子：
4.4
通讯作者：
Zhang L
中科院分区：
文献类型：
--
作者：
Pang S;Luo Z;Dong W;Gao S;Chen W;Liu N;Zhang X;Gao X;Li J;Gao K;Shi X;Guan F;Zhang L;Zhang L
TSPAN7敲除通过整合素β1/FAK/SRC信号通路在大鼠中引起asd样表型，这为TSPAN7在精神疾病中的作用提供了新的见解，突出了SRC作为潜在靶点。TSPAN7与包括自闭症谱系障碍（ASD）在内的多种神经系统疾病有关。然而，TSPAN7在ASD中的潜在突触机制尚不清楚。在这里，我们发现Tspan7基因敲除大鼠表现出asd样和id样的行为表型，大脑结构改变，包括海马和皮质体积减少，以及相关的病理改变，包括海马神经元数量减少，神经元复杂性，树突棘和突触相关蛋白减少。然后，我们发现TSPAN7缺失中断了整合素β1/FAK/SRC信号通路，随后PSD95、SYN和GluR1/2下调，这是突触完整性相关的关键蛋白。此外，SRC的再激活恢复了TSPAN7敲除脑原代神经元中突触完整性相关蛋白的表达。综上所述，我们的研究结果表明，敲除TSPAN7可能通过下调整合素β1/FAK/SRC信号通路导致大鼠ASD样行为和id样行为以及神经元突触受损，这可能是TSPAN7突变调控突触蛋白表达和ASD发病的新机制。这些发现为TSPAN7在精神疾病中的作用提供了新的见解，并突出了整合素β1/FAK/SRC作为ASD治疗的潜在靶点。
TSPAN7 knockout causes ASD-like phenotypes in rats through the integrin β1/FAK/SRC signal pathway, which provides novel insights into the role of TSPAN7 in psychiatric diseases, highlighting SRC as a potential target. TSPAN7 is related to various neurological disorders including autism spectrum disorder (ASD). However, the underlying synaptic mechanism of TSPAN7 in ASD is still unclear. Here, we showed that Tspan7 knockout rats exhibited ASD-like and ID-like behavioral phenotypes, brain structure alterations including decreased hippocampal and cortical volume, and related pathological changes including reduced hippocampal neurons number, neuronal complexity, dendritic spines, and synapse-associated proteins. Then, we found that TSPAN7 deletion interrupted the integrin β1/FAK/SRC signal pathway that was followed by the down-regulation of PSD95, SYN, and GluR1/2, which are key synaptic integrity-related proteins. Furthermore, reactivation of SRC restored the expression of synaptic integrity-related proteins in primary neurons of TSPAN7 knockout brains. Taken together, our results suggested that TSPAN7 knockout caused ASD-like and ID-like behaviors in rats and impaired neuronal synapses possibly through the down-regulation of the integrin β1/FAK/SRC signal pathway, which might be a new mechanism on regulation of synaptic proteins expression and on ASD pathogenesis by mutated TSPAN7. These findings provide novel insights into the role of TSPAN7 in psychiatric diseases and highlight integrin β1/FAK/SRC as a potential target for ASD therapy.
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影响因子：
3
作者：
Kadar, Andrea;Wittmann, Gabor;Liposits, Zsolt;Fekete, Csaba
通讯作者：
Fekete, Csaba
影响因子：
8.8
作者：
Block, Carina L.;Eroglu, Oznur;Mague, Stephen D.;Smith, Caroline J.;Ceasrine, Alexis M.;Sriworarat, Chaichontat;Blount, Cameron;Beben, Kathleen A.;Malacon, Karen E.;Ndubuizu, Nkemdilim;Talbot, Austin;Gallagher, Neil M.;Jo, Young Chan;Nyangacha, Timothy;Carlson, David E.;Dzirasa, Kafui;Eroglu, Cagla;Bilbo, Staci D.
通讯作者：
Bilbo, Staci D.
影响因子：
3.5
作者：
Berkel S;Tang W;Treviño M;Vogt M;Obenhaus HA;Gass P;Scherer SW;Sprengel R;Schratt G;Rappold GA
通讯作者：
Rappold GA
DOI：
10.3791/2270
发表时间：
2010-11-16
期刊：
Journal of visualized experiments : JoVE
影响因子：
--
作者：
Ippolito, Dominic M;Eroglu, Cagla
通讯作者：
Eroglu, Cagla
影响因子：
4
作者：
Abidi, FE;Holinski-Feder, E;Schwartz, CE
通讯作者：
Schwartz, CE