Dopamine/BDNF loss underscores narcosis cognitive impairment in divers: a proof of concept in a dry condition

Abstract

Purpose: Divers can experience cognitive impairment due to inert gas narcosis (IGN) at depth. Brain-derived neurotrophic factor (BDNF) rules neuronal connectivity/metabolism to maintain cognitive function and protect tissues against oxidative stress (OxS). Dopamine and glutamate enhance BDNF bioavailability. Thus, we hypothesized that lower circulating BDNF levels (via lessened dopamine and/or glutamate release) underpin IGN in divers, while testing if BDNF loss is associated with increased OxS.

Methods: To mimic IGN, we administered a deep narcosis test via a dry dive test (DDT) at 48 msw in a multiplace hyperbaric chamber to six well-trained divers. We collected: (1) saliva samples before DDT (T0), 25 msw (descending, T1), 48 msw (depth, T2), 25 msw (ascending, T3), 10 min after decompression (T4) to dopamine and/or reactive oxygen species (ROS) levels; (2) blood and urine samples at T0 and T4 for OxS too. We administered cognitive tests at T0, T2, and re-evaluated the divers at T4.

Results: At 48 msw, all subjects experienced IGN, as revealed by the cognitive test failure. Dopamine and total antioxidant capacity (TAC) reached a nadir at T2 when ROS emission was maximal. At decompression (T4), a marked drop of BDNF/glutamate content was evidenced, coinciding with a persisting decline in dopamine and cognitive capacity.

Conclusions: Divers encounter IGN at - 48 msw, exhibiting a marked loss in circulating dopamine levels, likely accounting for BDNF-dependent impairment of mental capacity and heightened OxS. The decline in dopamine and BDNF appears to persist at decompression; thus, boosting dopamine/BDNF signaling via pharmacological or other intervention types might attenuate IGN in deep dives.

Keywords: Brain-derived neurotrophic factor (BDNF); Deep diving; Dopamine; Narcosis; Reactive oxygen species (ROS).

Fig. 1

Experimental study design

Fig. 2

Bar charts (mean ± SD) of A labyrinth test score), B picture construction test score, at T0, T2, and T4; C BDNF, D glutamate, and E dopamine concentration in plasma collected at T0 and T4. Time course of F dopamine concentration in saliva at T0, T1, T2, T3, and T4. *p < 0.05, **p < 0.01 significantly different

Fig. 3

Bar chart (mean ± SD) of A ROS production rate. B Time course of ROS production rate. C Stacked plots of the EPR spectra show an increase of the signal amplitude (a. u.) at T4 (blu lines) with respect to T0 (black lines). The spectra are centered at g = 1.997. *p < 0.05 and **p < 0.0 are significantly different. D Bar chart of total antioxidant capacity (TAC). E Time course of total antioxidant capacity in saliva at T0, T1, T2, T3, and T4. F Bar chart of lipid peroxidation (8-isoprostane) in plasma collected at T0 and T4

Fig. 4

Panel plot of the relationship between ROS production rate and dopamine recorded at pre- (T0, gray circles) and post- (T4, green circles) session. The linear regression line (solid line) and the correlation coefficient (r) with statistical significance (*p < 0.05) is reported

Fig. 5

Bar charts (mean ± SD) of A NO metabolites (NOx), B nitrite (NO₂), and C inducible nitric oxide synthase (iNOS), collected at T0 and T4 *p < 0.05, significantly different

Fig. 6

Bar charts (mean ± SD) of A neopterin and B creatinine concentration, collected at T0 and T4. *p < 0.05, significantly different

Fig. 7

Scheme of deep narcosis test via a dry dive test (DDT) at 48 m in a multiplace hyperbaric chamber. The Inert Gas Narcosis (IGN) consists in a reversible depression of neuronal excitatory signaling - BDNF (−47%), Glutamate (−35%), Dopamine (−23%) -, and an imbalance between ROS and antioxidant defenses (i.e., ROS: +43% and TAC −10%), caused in particular by nitrogen and oxygen breathing at higher partial pressures. The influence on clinical presentation can include decreased cognitive performance. The onset varies, but can be seen around 30 msw or deeper