Caraci Filippo, Gulisano Walter, Guida Chiara A, Impellizzeri Agata A R, Drago Filippo, Puzzo Daniela, Palmeri Agostino
1] Department of Drug Sciences, University of Catania, Catania, Italy [2] IRCCS Associazione Oasi Maria S.S., Institute for Research on Mental Retardation and Brain Aging, Troina, Italy.
Department of Biomedical and Biotechnological Sciences - Section of Physiology, University of Catania, Catania, Italy.
Sci Rep. 2015 Jun 10;5:11252. doi: 10.1038/srep11252.
Transforming Growth Factor β1 (TGF-β1) is a well-known neuroprotective and neurotrophic factor demonstrated to play a role in synaptic transmission. However, its involvement in physiological mechanisms underlying synaptic plasticity and memory at hippocampal level has not been thoroughly investigated. Here, we examine the role of TGF-β1 in hippocampal long-term potentiation (LTP) and memory in adult wild type mice. Our data provide evidence that administration of exogenous TGF-β1 is able to convert early-phase-LTP into late-phase-LTP. Furthermore, we show that the block of the endogenous TGF-β1 signaling pathway by the specific TGF-β1 inhibitor SB431542, impairs LTP and object recognition memory. The latter impairment was rescued by administration of exogenous TGF-β1, suggesting that endogenously produced TGF-β1 plays a role in physiological mechanisms underlying LTP and memory. Finally, TGF-β1 functional effect correlates with an increased expression of the phosphorylated transcription factor cAMP-Responsive Element Binding protein.
转化生长因子β1（TGF-β1）是一种著名的神经保护和神经营养因子，已被证明在突触传递中发挥作用。然而，其在海马水平上参与突触可塑性和记忆的生理机制尚未得到充分研究。在此，我们研究了TGF-β1在成年野生型小鼠海马长时程增强（LTP）和记忆中的作用。我们的数据表明，外源性TGF-β1的给药能够将早期LTP转化为晚期LTP。此外，我们发现特异性TGF-β1抑制剂SB431542阻断内源性TGF-β1信号通路会损害LTP和物体识别记忆。外源性TGF-β1的给药挽救了后者的损伤，表明内源性产生的TGF-β1在LTP和记忆的生理机制中发挥作用。最后，TGF-β1的功能效应与磷酸化转录因子环磷酸腺苷反应元件结合蛋白的表达增加相关。
