Adenosine modulates excitatory synaptic transmission and suppresses neuronal death induced by ischaemia in rat spinal motoneurones

Abstract

Although adenosine is an important neuromodulator, its role in modulating motor functions at the level of the spinal cord is poorly understood. In the present study, we investigated the effects of adenosine on excitatory synaptic transmission and neuronal death induced by experimental ischaemia by using whole-cell patch-clamp recordings from lamina IX neurones in spinal cord slices. Adenosine significantly decreased the frequency of miniature excitatory postsynaptic currents (mEPSCs) in almost all neurones examined that could be mimicked by an A(1) receptor agonist, N (6)-cyclopentyladenosine (CPA), and inhibited by an A(1) receptor antagonist, 8-cyclopentyl-1, 3-dipropylxanthine (DPCPX). Interestingly, adenosine increased mEPSC frequency in the presence of DPCPX in a subpopulation of neurones. In these neurones, an A(2A) receptor agonist, 2-[4-(2-carbonylethyl)-phenethylamino]-5'-N-ethylcarboxamidoadenosine (CGS21680), increased mEPSC frequency. Adenosine also induced an outward current that was blocked by the addition of Cs(+) and tetraethylammonium into the patch-pipette solution and inhibited in the presence of Ba(2+). The adenosine-induced outward current was mimicked by CPA, but not CGS21680, and inhibited by DPCPX. Moreover, superfusing with ischaemia simulating medium (ISM) generated an agonal inward current in all of the neurones tested. The latencies of the inward currents induced by ISM were significantly prolonged by adenosine or CPA, but not by CGS21680. These results suggest that adenosine receptors are functionally expressed in both the pre- and postsynaptic sites of lamina IX neurones and that their activation may exert multiple effects on motor function. Moreover, this study has provided a cellular basis for an involvement of A(1) receptors in the neuroprotective actions of adenosine.

Hydrogen peroxide modulates synaptic transmission in ventral horn neurons of the rat spinal cord

“…), leading to presynaptic inhibition of excitatory transmission and eliciting an outward current in spinal VH neurons (Miyazaki et al . ). However, it is unclear why H 2 O 2 treatment in the presence of 2‐APB had no effect on R in even though an outward current and decrease of mEPSCs frequency were observed.…”

Suppression of adenosine 2a receptor (A2aR)-mediated adenosine signaling improves disease phenotypes in a mouse model of amyotrophic lateral sclerosis

“…How adenosine-induced A 2a R activation is toxic to spinal motor neurons remains unclear. As A 2a R activation is excitatory to spinal motor neurons (Miyazaki et al, 2008) and excitotoxicity is considered one of the primary mechanisms for spinal motor neuron degeneration (Cleveland and Rothstein, 2001), it is likely that elevated adenosine extensively stimulates pathologically increased A 2a R and subsequently contributes to motor neuron excitotoxicity. In addition, pharmacological inhibition of A 2a R-mediated transactivation of TrkB protects primary motor neurons from excitotoxic insults in cultures (Mojsilovic-Petrovic et al, 2006).…”

Selective adenosine A2Areceptor agonists and antagonists protect against spinal cord injury through peripheral and central effects

“…The A 2A receptor agonist, CGS21680, increases miniature excitatory postsynaptic currents in SC in the lamina IX neurones of spinal motoneurons, indicating that A 2A receptors modulate excitatory synaptic transmission [40]. We have demonstrated that A 2A antagonists reduce glutamate outflow in the first hours after brain ischemia [20].…”