Transforming Growth Factor β1 (TGF-β1) is a cytokine involved in the control of cell growth, differentiation as well as immune suppression and repair after injury. In addition to its well-known neuroprotective and neurotrophic properties, it has been recently reported a possible role of TGF-β1 in synaptic transmission. However, its involvement in physiological mechanisms underlying synaptic plasticity and memory at hippocampal level has not been thoroughly investigated. We examined the role of TGF-β1 in hippocampal long-term potentiation (LTP) and memory in adult wild type mice. We first assessed the effect of exogenous TGF-β1 on CA1 LTP and phosphorylation of the transcription factor CREB. Then, we investigated the role of endogenous TGF-β1 in hippocampal synaptic plasticity, recognition memory and p-CREB levels by blocking its signaling pathway with the selective inhibitor SB431542. Finally, we examined the involvement of p-SMAD2, a TGF-β1 downstream pathway effector. We found that exogenous TGF-β1 converted early-phase-LTP into late-phase-LTP. Furthermore, the block of the endogenous TGF-β1 signaling pathway by SB431542, impaired LTP and object recognition memory that were rescued by administration of exogenous TGF-β1. These TGF-β1 functional effects correlated with the expression of phospho-CREB and phospho-SMAD2. Our findings suggest that endogenously produced TGF-β1 plays a role in physiological mechanisms underlying LTP and memory.

Physiological role of TGF-β1 in hippocampal synaptic plasticity and memory

PUZZO, DANIELA;DRAGO, Filippo;PALMERI, Agostino;CARACI, FILIPPO
2015-01-01

Abstract

Transforming Growth Factor β1 (TGF-β1) is a cytokine involved in the control of cell growth, differentiation as well as immune suppression and repair after injury. In addition to its well-known neuroprotective and neurotrophic properties, it has been recently reported a possible role of TGF-β1 in synaptic transmission. However, its involvement in physiological mechanisms underlying synaptic plasticity and memory at hippocampal level has not been thoroughly investigated. We examined the role of TGF-β1 in hippocampal long-term potentiation (LTP) and memory in adult wild type mice. We first assessed the effect of exogenous TGF-β1 on CA1 LTP and phosphorylation of the transcription factor CREB. Then, we investigated the role of endogenous TGF-β1 in hippocampal synaptic plasticity, recognition memory and p-CREB levels by blocking its signaling pathway with the selective inhibitor SB431542. Finally, we examined the involvement of p-SMAD2, a TGF-β1 downstream pathway effector. We found that exogenous TGF-β1 converted early-phase-LTP into late-phase-LTP. Furthermore, the block of the endogenous TGF-β1 signaling pathway by SB431542, impaired LTP and object recognition memory that were rescued by administration of exogenous TGF-β1. These TGF-β1 functional effects correlated with the expression of phospho-CREB and phospho-SMAD2. Our findings suggest that endogenously produced TGF-β1 plays a role in physiological mechanisms underlying LTP and memory.
TGF-β1; long-term potentiation; memory
File in questo prodotto:
Non ci sono file associati a questo prodotto.

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/20.500.11769/73353
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus ND
  • ???jsp.display-item.citation.isi??? ND
social impact