Astroglial Control of the Antidepressant-Like Effects of Prefrontal Cortex Deep Brain Stimulation

TY - JOUR

T1 - Astroglial Control of the Antidepressant-Like Effects of Prefrontal Cortex Deep Brain Stimulation

AU - Etiévant, A

AU - Oosterhof, C

AU - Bétry, C

AU - Abrial, E

AU - Novo-Perez, M

AU - Rovera, R

AU - Scarna, H

AU - Devader, C

AU - Mazella, J

AU - Wegener, G

AU - Sánchez, C

AU - Dkhissi-Benyahya, O

AU - Gronfier, C

AU - Coizet, V

AU - Beaulieu, J M

AU - Blier, P

AU - Lucas, G

AU - Haddjeri, N

PY - 2015/8

Y1 - 2015/8

N2 - Although deep brain stimulation (DBS) shows promising efficacy as a therapy for intractable depression, the neurobiological bases underlying its therapeutic action remain largely unknown. The present study was aimed at characterizing the effects of infralimbic prefrontal cortex (IL-PFC) DBS on several pre-clinical markers of the antidepressant-like response and at investigating putative non-neuronal mechanism underlying DBS action. We found that DBS induced an antidepressant-like response that was prevented by IL-PFC neuronal lesion and by adenosine A1 receptor antagonists including caffeine. Moreover, high frequency DBS induced a rapid increase of hippocampal mitosis and reversed the effects of stress on hippocampal synaptic metaplasticity. In addition, DBS increased spontaneous IL-PFC low-frequency oscillations and both raphe 5-HT firing activity and synaptogenesis. Unambiguously, a local glial lesion counteracted all these neurobiological effects of DBS. Further in vivo electrophysiological results revealed that this astrocytic modulation of DBS involved adenosine A1 receptors and K(+) buffering system. Finally, a glial lesion within the site of stimulation failed to counteract the beneficial effects of low frequency (30 Hz) DBS. It is proposed that an unaltered neuronal-glial system constitutes a major prerequisite to optimize antidepressant DBS efficacy. It is also suggested that decreasing frequency could heighten antidepressant response of partial responders.

AB - Although deep brain stimulation (DBS) shows promising efficacy as a therapy for intractable depression, the neurobiological bases underlying its therapeutic action remain largely unknown. The present study was aimed at characterizing the effects of infralimbic prefrontal cortex (IL-PFC) DBS on several pre-clinical markers of the antidepressant-like response and at investigating putative non-neuronal mechanism underlying DBS action. We found that DBS induced an antidepressant-like response that was prevented by IL-PFC neuronal lesion and by adenosine A1 receptor antagonists including caffeine. Moreover, high frequency DBS induced a rapid increase of hippocampal mitosis and reversed the effects of stress on hippocampal synaptic metaplasticity. In addition, DBS increased spontaneous IL-PFC low-frequency oscillations and both raphe 5-HT firing activity and synaptogenesis. Unambiguously, a local glial lesion counteracted all these neurobiological effects of DBS. Further in vivo electrophysiological results revealed that this astrocytic modulation of DBS involved adenosine A1 receptors and K(+) buffering system. Finally, a glial lesion within the site of stimulation failed to counteract the beneficial effects of low frequency (30 Hz) DBS. It is proposed that an unaltered neuronal-glial system constitutes a major prerequisite to optimize antidepressant DBS efficacy. It is also suggested that decreasing frequency could heighten antidepressant response of partial responders.

U2 - 10.1016/j.ebiom.2015.06.023

DO - 10.1016/j.ebiom.2015.06.023

M3 - Journal article

C2 - 26425697

SN - 2352-3964

VL - 2

SP - 896

EP - 906

JO - EBioMedicine

JF - EBioMedicine

IS - 8

ER -