Abstract
Propofol inhibits long-term potentiation (LTP) in the hippocampal CA1 region and impedes episodic memory formation. However, the molecular mechanisms involved in the effect of propofol are still poorly understood. It had been reported that propofol inhibited cAMP response element binding protein signaling, which was proposed to contribute to memory retention impairment in rats. Here, we first demonstrated that propofol perfusion could inhibit forskolin induced LTP in the rat hippocampal CA1 slices. Propofol also reduced the level of cAMP, which could be reversed by non-selective PDE inhibitor IBMX. We further discovered that propofol could increase both PDE4 activity and PDE4AX protein expressions in the hippocampal CA1 region. Furthermore, pretreatment of rolipram, a PDE4 inhibitor, rescued propofol induced inhibition of CA1 LTP and the impairment of hippocampus-dependent memory formation in rats. Thus, our results suggest that reduced levels of cAMP by increasing PDE4 activity and PDE4AX protein expressions in the hippocampal CA1 region plays an important role in the propofol-induced amnesia.
Highlights
Propofol, the most widely used intravenous general anesthetic, can impede episodic memory formation even at sedative doses (Pang et al, 1993; Veselis et al, 2004; Zhang et al, 2013)
We investigated whether the differentiation of propofol on two different protocols induced Long-term potentiation (LTP) was due to modulation of the cAMP levels in hippocampal neurons
Propofol (50 μM) pretreatment for 20 min significantly inhibited the FSK induced increases of the field excitatory post-synaptic potentials (fEPSPs) slope (108 ± 8% (n = 6) of baseline vs. 139 ± 8% (n = 6) in FSK alone group, p < 0.05) (Figure 1). These results suggest that propofol is likely to influence the cAMP pathway during the LTP induction in the hippocampal CA1 region
Summary
The most widely used intravenous general anesthetic, can impede episodic memory formation even at sedative doses (Pang et al, 1993; Veselis et al, 2004; Zhang et al, 2013). Theta burst stimulation induced LTP in hippocampal CA1 region is reported cAMP signaling dependent and sensitive to be affected by GABA receptor activation (Nguyen and Kandel, 1997; Staubli et al, 1999; Costa and Grybko, 2005). High frequency stimulation induced LTP is cAMP signaling independent and not sensitive to being affected by GABA receptor activation. One of the differences, such as cAMP signaling and effect by the GABA receptor activation between these two forms of LTP, could likely be a contributor to this differential effect of propofol on LTP as well as memory formation
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