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

Etiévant A, Oosterhof C, Bétry C, Abrial E, Novo-Perez M, Rovera R, Scarna H, Devader C, Mazella J, Wegener G, Sánchez C, Dkhissi-Benyahya O, Gronfier C, Coizet V, Beaulieu JM, Blier P, Lucas G, Haddjeri N - EBioMedicine (2015)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: 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.

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.

No MeSH data available.


Related in: MedlinePlus

Effects of a glial lesion on IL-DBS-induced enhancement of slow oscillatory activity. Spontaneous local field potentials and relative power spectra of low frequency bands (0–21 Hz) within the IL PFC in sham (A) and IL-DBS-treated rats (B). (C) Percentage of total power spectrum showed that IL-DBS significantly enhanced the δ, θ, α, and β frequencies, an effect abolished by glial lesion (***p < 0.001 vs sham, n = 4–5 rats per group).
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f0020: Effects of a glial lesion on IL-DBS-induced enhancement of slow oscillatory activity. Spontaneous local field potentials and relative power spectra of low frequency bands (0–21 Hz) within the IL PFC in sham (A) and IL-DBS-treated rats (B). (C) Percentage of total power spectrum showed that IL-DBS significantly enhanced the δ, θ, α, and β frequencies, an effect abolished by glial lesion (***p < 0.001 vs sham, n = 4–5 rats per group).

Mentions: Disrupted low oscillatory activity has been reported in animal model of depression (Voget et al., 2015, Gazit et al., 2015). As illustrated in Fig. 4, analysis of spontaneous local field potentials and relative power spectra revealed that IL-DBS increased low frequency bands (0–21 Hz) within the IL PFC compared to sham rats (Fig. 4A and B). Analysis of the percentage of total power spectrum (Fig. 4C) showed that IL-DBS significantly enhanced the δ, θ, α, and β frequencies in comparison to non-stimulated animals. Importantly, the latter effect was significantly abolished in l-AAA infused animals while a glial lesion had no effect by itself on slow waves activities recorded in the IL-PFC.


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

Etiévant A, Oosterhof C, Bétry C, Abrial E, Novo-Perez M, Rovera R, Scarna H, Devader C, Mazella J, Wegener G, Sánchez C, Dkhissi-Benyahya O, Gronfier C, Coizet V, Beaulieu JM, Blier P, Lucas G, Haddjeri N - EBioMedicine (2015)

Effects of a glial lesion on IL-DBS-induced enhancement of slow oscillatory activity. Spontaneous local field potentials and relative power spectra of low frequency bands (0–21 Hz) within the IL PFC in sham (A) and IL-DBS-treated rats (B). (C) Percentage of total power spectrum showed that IL-DBS significantly enhanced the δ, θ, α, and β frequencies, an effect abolished by glial lesion (***p < 0.001 vs sham, n = 4–5 rats per group).
© Copyright Policy - CC BY-NC-ND
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4563138&req=5

f0020: Effects of a glial lesion on IL-DBS-induced enhancement of slow oscillatory activity. Spontaneous local field potentials and relative power spectra of low frequency bands (0–21 Hz) within the IL PFC in sham (A) and IL-DBS-treated rats (B). (C) Percentage of total power spectrum showed that IL-DBS significantly enhanced the δ, θ, α, and β frequencies, an effect abolished by glial lesion (***p < 0.001 vs sham, n = 4–5 rats per group).
Mentions: Disrupted low oscillatory activity has been reported in animal model of depression (Voget et al., 2015, Gazit et al., 2015). As illustrated in Fig. 4, analysis of spontaneous local field potentials and relative power spectra revealed that IL-DBS increased low frequency bands (0–21 Hz) within the IL PFC compared to sham rats (Fig. 4A and B). Analysis of the percentage of total power spectrum (Fig. 4C) showed that IL-DBS significantly enhanced the δ, θ, α, and β frequencies in comparison to non-stimulated animals. Importantly, the latter effect was significantly abolished in l-AAA infused animals while a glial lesion had no effect by itself on slow waves activities recorded in the IL-PFC.

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: 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.

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.

No MeSH data available.


Related in: MedlinePlus