Transcutaneous spinal direct current stimulation (tsDCS) improves ventilation in obesity hypoventilation syndrome mice models - 17/02/23

Central hypoventilation syndromes (CHS) are genetic or acquired neurorespiratory pathologies characterized by central hypoventilation which can be associated with reduction or absence of CO2/pH chemosensitivity; without known curative treatment, management is assisted ventilation. Of the various documented CHS, obesity hypoventilation syndrome (OHS) is defined by a body mass index>30kg/m² and day-time pCO2>45mm Hg in absence of other known causes of alveolar hypoventilation. OHS and leptinergic systems are closely linked but causes of central hypoventilation are yet to be explained. Its prevalence is 10–20% amongst obese patients. In this context, we aim to search for a respiratory benefit in OHS preclinical mice model induced by cervical tsDCS, a non-invasive approach for which our unit has provided clinical proof of interest to increase ventilation in healthy subjects.

In all, 10 to 25-week-old B6. V Lepob/ob JRj male mice were used as OHS preclinical models. Under isoflurane anesthesia mice either received a cutaneous cervical tsDCS for 20minutes at 2mA during 5 consecutive days (tsDCS) or none (sham). Ventilation was recorded by plethysmography (DSI system) and O2 saturation was measured (StarrLab MouseOx Plus system). tsDCS effects were explored by comparing tsDCS with sham values (intergroup comparisons) for minute ventilation (V̇E), hypopnea duration and O2 saturation. cFOS and ΔFOSB immunohistodetections were made to search for neuroplasticity in the ponto-medullary respiratory network by comparing tsDCS and sham tissues. These detections were associated with phenotypical detections (tyrosine hydroxylase, serotonin…) to characterize the neurons engaged in neuroplasticity. RNAsequencing was performed in the pons and medulla oblongata to search for modification of gene expression induced by tsDCS.

In all, 5-day tsDCS (D1-5) procedures significantly improved Lepob/ob mice's ventilation: 1/V̇E increased on D5 in tsDCS mice compared to sham mice (+118.2%); 2/hypopnea significantly diminished on D1 and D3 in tsDCS mice compared to sham mice (11.09% and 9.81%). 3/tsDCS mice spent fewer time with SpO2<0.95% than sham mice on D4 (36.84%). P<0.05.

Our data suggest that cervical tsDCS applied for 5 consecutive days leads to ventilatory plasticity through an increase in ventilation. This was confirmed by a decrease in time spent with SpO2 under 95%. In this context, our immunohistochemical studies should allow us to identify and characterize the neuronal groups of the ponto-medullary respiratory network involved in the implementation of ventilatory plasticity induced by tsDCS. In parallel, data obtained by RNAsequencing should allow us to identify the molecular pathways involved in this neuroplasticity.