TY - JOUR
T1 - Obstructive sleep apnea is associated with altered midbrain chemical concentrations
AU - Macey, Paul M.
AU - Sarma, Manoj K.
AU - Prasad, Janani P.
AU - Ogren, Jennifer A.
AU - Aysola, Ravi
AU - Harper, Ronald M.
AU - Thomas, M. Albert
N1 - Funding Information:
Funding: This work was supported by the National Institutes of Health – United States [ NR-013693 , HL-131010 ].
Publisher Copyright:
© 2017 IBRO
PY - 2017/11/5
Y1 - 2017/11/5
N2 - Obstructive sleep apnea (OSA) is accompanied by altered structure and function in cortical, limbic, brainstem, and cerebellar regions. The midbrain is relatively unexamined, but contains many integrative nuclei which mediate physiological functions that are disrupted in OSA. We therefore assessed the chemistry of the midbrain in OSA in this exploratory study. We used a recently developed accelerated 2D magnetic resonance spectroscopy (2D-MRS) technique, compressed sensing-based 4D echo-planar J-resolved spectroscopic imaging (4D-EP-JRESI), to measure metabolites in the midbrain of 14 OSA (mean age ± SD:54.6 ± 10.6 years; AHI:35.0 ± 19.4; SAO2 min:83 ± 7%) and 26 healthy control (50.7 ± 8.5 years) subjects. High-resolution T1-weighted scans allowed voxel localization. MRS data were processed with custom MATLAB-based software, and metabolite ratios calculated with respect to the creatine peak using a prior knowledge fitting (ProFit) algorithm. The midbrain in OSA showed decreased N-acetylaspartate (NAA; OSA:1.24 ± 0.43, Control:1.47 ± 0.41; p = 0.03; independent samples t-test), a marker of neuronal viability. Increased levels in OSA over control subjects appeared in glutamate (Glu; OSA:1.23 ± 0.57, Control:0.98 ± 0.33; p = 0.03), ascorbate (Asc; OSA:0.56 ± 0.28, Control:0.42 ± 0.20; (50.7 ± 8.5 years; p = 0.03), and myo-inositol (mI; OSA:0.96 ± 0.48, Control:0.72 ± 0.35; p = 0.03). No differences between groups appeared in γ-aminobutyric acid (GABA) or taurine. The midbrain in OSA patients shows decreased NAA, indicating neuronal injury or dysfunction. Higher Glu levels may reflect excitotoxic processes and astrocyte activation, and higher mI is also consistent with glial activation. Higher Asc levels may result from oxidative stress induced by intermittent hypoxia in OSA. Additionally, Asc and Glu are involved with glutamatergic processes, which are likely upregulated in the midbrain nuclei of OSA patients. The altered metabolite levels help explain dysfunction and structural deficits in the midbrain of OSA patients.
AB - Obstructive sleep apnea (OSA) is accompanied by altered structure and function in cortical, limbic, brainstem, and cerebellar regions. The midbrain is relatively unexamined, but contains many integrative nuclei which mediate physiological functions that are disrupted in OSA. We therefore assessed the chemistry of the midbrain in OSA in this exploratory study. We used a recently developed accelerated 2D magnetic resonance spectroscopy (2D-MRS) technique, compressed sensing-based 4D echo-planar J-resolved spectroscopic imaging (4D-EP-JRESI), to measure metabolites in the midbrain of 14 OSA (mean age ± SD:54.6 ± 10.6 years; AHI:35.0 ± 19.4; SAO2 min:83 ± 7%) and 26 healthy control (50.7 ± 8.5 years) subjects. High-resolution T1-weighted scans allowed voxel localization. MRS data were processed with custom MATLAB-based software, and metabolite ratios calculated with respect to the creatine peak using a prior knowledge fitting (ProFit) algorithm. The midbrain in OSA showed decreased N-acetylaspartate (NAA; OSA:1.24 ± 0.43, Control:1.47 ± 0.41; p = 0.03; independent samples t-test), a marker of neuronal viability. Increased levels in OSA over control subjects appeared in glutamate (Glu; OSA:1.23 ± 0.57, Control:0.98 ± 0.33; p = 0.03), ascorbate (Asc; OSA:0.56 ± 0.28, Control:0.42 ± 0.20; (50.7 ± 8.5 years; p = 0.03), and myo-inositol (mI; OSA:0.96 ± 0.48, Control:0.72 ± 0.35; p = 0.03). No differences between groups appeared in γ-aminobutyric acid (GABA) or taurine. The midbrain in OSA patients shows decreased NAA, indicating neuronal injury or dysfunction. Higher Glu levels may reflect excitotoxic processes and astrocyte activation, and higher mI is also consistent with glial activation. Higher Asc levels may result from oxidative stress induced by intermittent hypoxia in OSA. Additionally, Asc and Glu are involved with glutamatergic processes, which are likely upregulated in the midbrain nuclei of OSA patients. The altered metabolite levels help explain dysfunction and structural deficits in the midbrain of OSA patients.
KW - autonomic
KW - intermittent hypoxia
KW - magnetic resonance spectroscopy
KW - periaqueductal gray
KW - respiration
KW - sleep-disordered breathing
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U2 - 10.1016/j.neuroscience.2017.09.001
DO - 10.1016/j.neuroscience.2017.09.001
M3 - Article
C2 - 28893651
AN - SCOPUS:85029676250
SN - 0306-4522
VL - 363
SP - 76
EP - 86
JO - Neuroscience
JF - Neuroscience
ER -