A key role for TGF-ß1 in hippocampal synaptic plasticity and memory.

ABSTRACT

Transforming Growth Factor ß1 (TGF-ß1) 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-ß1 in hippocampal long-term potentiation (LTP) and memory in adult wild type mice. Our data provide evidence that administration of exogenous TGF-ß1 is able to convert early-phase-LTP into late-phase-LTP. Furthermore, we show that the block of the endogenous TGF-ß1 signaling pathway by the specific TGF-ß1 inhibitor SB431542, impairs LTP and object recognition memory. The latter impairment was rescued by administration of exogenous TGF-ß1, suggesting that endogenously produced TGF-ß1 plays a role in physiological mechanisms underlying LTP and memory. Finally, TGF-ß1 functional effect correlates with an increased expression of the phosphorylated transcription factor cAMP-Responsive Element Binding protein.