Electroconvulsive therapy: a novel hypothesis for the involvement of purinergic signalling

Abstract

It is proposed that ATP is released from both neurons and glia during electroconvulsive therapy (ECT) and that this leads to reduction of depressive behaviour via complex stimulation of neurons and glia directly via P2X and P2Y receptors and also via P1 receptors after extracellular breakdown of ATP to adenosine. In particular, A 1 adenosine receptors inhibit release of excitatory transmitters, and A 2A and P2Y receptors may modulate the release of dopamine. Sequential ECT may lead to changes in purinoceptor expression in mesolimbic and mesocortical regions of the brain implicated in depression and other mood disorders. In particular, increased expression of P2X7 receptors on glial cells would lead to increased release of cytokines, chemokines and neurotrophins. In summary, we suggest that ATP release following ECT involves neurons, glial cells and neuron-glial interactions acting via both P2 and after breakdown to adenosine via P1 receptors. We suggest that ecto-nucleotidase inhibitors (increasing available amounts of ATP) and purinoceptor agonists may enhance the antidepressive effect of ECT.

Signaling pathways regulating Homer1a expression: implications for antidepressant therapy

“…Conversely, A 1 RKO mice displayed an increased depressive-like behavior and were resistant to the antidepressant effects of SD (Serchov et al, 2015a). Interestingly, Homer1a is up-regulated by SD and ECT, antidepressant therapies also associated with increased A 1 R signaling (Sakagami et al, 2005;Conti et al, 2007;Elmenhorst et al, 2007Elmenhorst et al, , 2009Sadek et al, 2011). We described that Homer1a expression is increased in the brain of A1 mice, while A 1 RKO mice have low Homer1a levels and display no induction of Homer1a in mPFC after SD (Serchov et al, 2015a).…”

“…However, the upstream signaling pathways that regulate or induce Homer1a expression are still not well investigated. (van Calker and Biber, 2005;Burnstock et al, 2011;Sadek et al, 2011). Adenosine is a neuromodulator in the central nervous system exhibiting anticonvulsive, neuroprotective and sleep regulating properties (Fredholm et al, 2005 (Fredholm et al, 2001).…”

“…It is known that SD evokes an increased release of adenosine in the brain and up-regulation of adenosine A 1 receptors (A 1 R) in rodents and humans Elmenhorst et al, 2007Elmenhorst et al, , 2009. Two other non-pharmacological interventions for depression ECT and deep brain stimulation are associated with an increased release of adenosine and stimulation of A 1 R (van Calker and Biber, 2005;Bekar et al, 2008;Hamani et al, 2010;Sadek et al, 2011). Furthermore, direct experimental data indicate that adenosine agonists have antidepressant activity (Hines et al, 2013).…”

Purinergic system dysfunction in mood disorders: a key target for developing improved therapeutics

“…Moreover, ATP release is thought to occur from neurons and glial cells during electroconvulsive therapy (ECT), resulting in the initial activation of P2 receptors and subsequent activation of P1 receptors following degradation of ATP into adenosine. Sadek and colleagues proposed that the antidepressant effects of this therapy would result from the co-release of ATP with dopamine (Sadek et al, 2011). On the one hand, the released ATP could stimulate P2X7 receptors, thereby affecting depressive symptoms (Sadek et al, 2011).…”

“…Sadek and colleagues proposed that the antidepressant effects of this therapy would result from the co-release of ATP with dopamine (Sadek et al, 2011). On the one hand, the released ATP could stimulate P2X7 receptors, thereby affecting depressive symptoms (Sadek et al, 2011). On the other hand, P2Y1 receptors expressed by neuronal cells have also been associated with both anxiolytic and antidepressant effects (Kittner et al, 2003; Taayedi, 2007).…”