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EBioMedicine. 2015 Jul 7;2(8):898-908. doi: 10.1016/j.ebiom.2015.06.023. eCollection 2015 Aug.

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

Author information

1
Stem Cell and Brain Research Institute, INSERM U846, 69500 Bron, France ; Université de Lyon, Université Lyon 1, 69373 Lyon, France ; Department of Psychiatry and Neurosciences, Faculty of Medicine, Laval University-IUSMQ, Québec City, Québec, Canada.
2
Institute of Mental Health Research, University of Ottawa, Ottawa, Ontario, Canada.
3
Stem Cell and Brain Research Institute, INSERM U846, 69500 Bron, France ; Université de Lyon, Université Lyon 1, 69373 Lyon, France.
4
Institut de Pharmacologie Moléculaire et Cellulaire, Centre National de la Recherche Scientifique, UMR6097, Université de Nice Sophia Antipolis, 06560 Valbonne, France.
5
Department of Clinical Medicine, Translational Neuropsychiatry Unit, Aarhus University, Skovagervej 2, DK-8240 Risskov, Denmark.
6
Neuropharmacology, Lundbeck Research USA, Paramus, NJ, USA.
7
INSERM U836, GIN, Univ. Grenoble Alpes, F-38000 Grenoble, France.
8
Department of Psychiatry and Neurosciences, Faculty of Medicine, Laval University-IUSMQ, Québec City, Québec, Canada.
9
Stem Cell and Brain Research Institute, INSERM U846, 69500 Bron, France ; Université de Lyon, Université Lyon 1, 69373 Lyon, France ; Institut François Magendie, INSERM U862, Université de Bordeaux, 33077 Bordeaux, France.

Abstract

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.

KEYWORDS:

Astrocytes; DBS, deep brain stimulation; Deep brain stimulation; Depression; HFS, high frequency stimulation; IL-PFC, infralimbic prefrontal cortex; LFS, low frequency stimulation; PCPA, 4-chloro-dl-phenylalanine methyl ester; Prefrontal cortex; Serotonin; fEPSP, field excitatory post-synaptic potential; l-AAA, l-alpha-aminoadipic acid

PMID:
26425697
PMCID:
PMC4563138
DOI:
10.1016/j.ebiom.2015.06.023
[Indexed for MEDLINE]
Free PMC Article

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