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

作者：Etievant A; Oosterhof C; Betry C; Abrial E; Novo Perez M; Rovera R; Scarna H; Devader C; Mazella J; Wegener G; Sanchez C; Dkhissi Benyahya O; Gronfier C; Coizet V; Beaulieu J M; Blier P; Lucas G; Haddjeri N^*

来源：EBioMedicine, 2015, 2(8): 898-908.

DOI：10.1016/j.ebiom.2015.06.023

• Deep brain stimulation
• Depression
• Astrocytes
• Prefrontal cortex
• Serotonin

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 A(1) 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 synapto-genesis. 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.

• 出版日期2015-8