Citations

AbstractMitochondrial defects associated with respiratory chain complex I deficiency lead to heterogeneous fatal syndromes. While the role of NDUFS8, an essential subunit of the core assembly of the complex I, is established in mitochondrial diseases, the mechanisms underlying neuropathology are poorly understood. We developed a Drosophila model of NDUFS8 deficiency by knocking down the expression of its fly homologue in neurons or in glial cells. Downregulating ND23 in neurons resulted in shortened lifespan, and decreased locomotion. Although total brain ATP levels were decreased, histological analysis did not reveal any signs of neurodegeneration except for photoreceptors of the retina. Interestingly, ND23 deficiency‐associated phenotypes were rescued by overexpressing the glucose transporter hGluT3 demonstrating that boosting glucose metabolism in neurons was sufficient to bypass altered mitochondrial functions and to confer neuroprotection. We then analyzed the consequences of ND23 knockdown in glial cells. In contrast to neuronal knockdown, loss of ND23 in glia did not lead to significant behavioral defects nor to reduced lifespan, but induced brain degeneration, as visualized by numerous vacuoles found all over the nervous tissue. This phenotype was accompanied by the massive accumulation of lipid droplets at the cortex‐neuropile boundaries, suggesting an alteration of lipid metabolism in glia. These results demonstrate that complex I deficiency triggers metabolic alterations both in neurons and glial cells which may contribute to the neuropathology.

Background: The human sulfatase 1 (SULF1) and sulfatase 2 (SULF2) genes modulate cell signaling and homeostasis in many tissues. Gene expression analyses have implicated SULF2 in disease pathogenesis, including Alzheimer’s disease (AD), but changes in brain SULF2 expression have not been directly established. Objective: To investigate the expression of SULF1 and SULF2 in brain tissues from AD cases and cognitively normal controls. Methods: Autopsy tissue from AD cases ( n = 20) and age-and gender-matched cognitively normal controls ( n = 20) were identified from the Mayo Clinic Alzheimer’s Disease Patient Registry neuropathology database. Tissue slides were stained for SULF1 and SULF2 protein expression in the hippocampus and frontal lobe and an expression score computed from the proportion of cells stained and the intensity of staining (range 0 [no expression] to 9 [marked expression]). Results: SULF2 expression was reduced in AD cases. Compared to cognitively normal controls, SULF2 expression in AD cases was significantly decreased in the hippocampal Cornu Ammonis (CA) (mean score of 6.5 in cases versus 8.3 in controls; p = 0.003), in the gray matter of the parahippocampal gyrus (5.6 in cases versus 7.6 in controls; p = 0.003), and in the frontal lobe gray matter (5.4 in cases versus 7.4 in controls; p = 0.002). There was no difference in SULF1 expression in the hippocampus or frontal lobe of AD cases and controls. As expected there were no differences in SULF1 or SULF2 expression in white matter in AD cases compared to cognitively normal controls. Conclusion: Decreased SULF2 in specific regions of the brain occurs in AD.

Resting-state functional magnetic resonance imaging (rs-fMRI) is used to interrogate the functional connectivity and network organization amongst brain regions. Functional connectivity is determined by measuring the extent of synchronization in the spontaneous fluctuations of blood oxygenation level dependent (BOLD) signal. Here, we review current rs-fMRI studies in headache disorders including migraine, trigeminal autonomic cephalalgias, and medication overuse headache. We discuss (1) brain network alterations that are shared amongst the different headache disorders and (2) network abnormalities distinct to each headache disorder. In order to focus the section on migraine, the headache disorder that has been most extensively studied, we chose to include articles that interrogated functional connectivity: (i) during the attack phase; (ii) in migraine patients with aura compared to migraine patients without aura; and (iii) of regions within limbic, sensory, motor, executive and default mode networks and those which participate in multisensory integration. The results of this review show that headache disorders are associated with atypical functional connectivity of regions associated with pain processing as well as atypical functional connectivity of multiple core resting state networks such as the salience, sensorimotor, executive, attention, limbic, visual, and default mode networks.

Objective To investigate differences in cortical thickness in patients with persistent post‐traumatic headache (PPTH) relative to healthy controls and to interrogate whether cortical morphology relates to headache burden (headache frequency, years with post‐traumatic headache, PTH) in patients with PPTH. Background PTHs are one of the most common symptoms following concussion. In some patients, PTHs continue for longer than three months and are classified as PPTH. This study has two main goals: (1) To delineate the neuropathology of PPTH, by interrogating differences in cortical thickness in patients with PPTH relative to healthy controls. (2) To interrogate potential associations between brain morphology and headache burden in patients with PPTH by examining whether cortical thickness relates to frequency of headaches or years lived with PTH. Methods Adults with PPTH diagnosed according to ICHD 3 beta diagnostic criteria and healthy controls underwent brain MRI on a 3 Tesla scanner. Vertex‐by‐vertex whole brain estimates of cortical thickness were automatically calculated using FreeSurfer v5.3. Differences in cortical thickness in patients with PPTH relative to healthy controls were determined using a general linear model design. Associations were explored between regional clusters where patients with PPTH showed cortical thickness differences compared with healthy controls with headache frequency and years lived with PPTH. Results This study included 33 patients with PPTH and 33 healthy control subjects (healthy controls: median age = 33.0, IQR = 15.5; patients with PPTH: median age = 36.0, IQR = 20.5; P = .56). Patients with PPTH had less cortical thickness relative to healthy controls in the left and right superior frontal, caudal middle frontal, and precentral cortex as well as less cortical thickness in the right supramarginal, right superior and inferior parietal, and right precuneus region ( P < .05, Monte Carlo corrected for multiple comparisons). There were no regions where patients with PPTH had more cortical thickness relative to healthy controls. A correlation analysis of regions that showed less cortical thickness in patients with PPTH demonstrated a negative correlation between left and right superior frontal thickness with headache frequency ( P < .05). There was no association between regional cortical thickness and years lived with PPTH. Conclusion Compared with healthy controls, patients with PPTH had less cortical thickness in bilateral frontal regions and right hemisphere parietal regions. For patients with PPTH, more frequent headaches were related to less thickness in the left and right superior frontal regions, potentially indicating that brain morphology changes in the superior frontal regions in patients with PPTH are modified by headache frequency.

AbstractObjective:The aim of the study was to determine the association between self-reported vasomotor symptoms (VMS) and obstructive sleep apnea (OSA) risk.Methods:The STOP-BANG to evaluate OSA and Menopause Rating Scale (MRS) were administered to 2,935 women seen in the Women's Health Clinic at Mayo Clinic in Rochester, MN, between May 2015 and December 2016. Of these, 1,691 women were included in the analysis. Total MRS and VMS ratings were compared using logistic regression, with age, smoking, and body mass index (BMI) included as covariates between women at intermediate/high risk versus low risk for OSA.Results:Total MRS scores were significantly higher in women with intermediate/high-risk OSA scores versus those with low-risk scores [mean (SD): 16.8 (8.0) vs 12.9 (7.0),P < 0.001]. Women at intermediate/high OSA risk were older, had more education, self-reported hypertension, BMI >35 kg/m2, and were less likely to be married or employed. Self-reported severe/very severe VMS were significantly associated with intermediate/high risk versus low risk for OSA (26.6% vs 15.0%;P < 0.001). After adjusting for age, BMI, smoking status, and self-reported hypertension, the odds of having intermediate/high risk for OSA were 1.87 times higher for those with severe/very severe VMS compared with those with none/mild/moderate VMS (95% CI, 1.29-2.71,P < 0.001). This association persisted upon subgroup analysis based on BMI <25 kg/m2(odds ratio 2.15; 95% CI, 1.12-4.16,P= 0.022).Conclusions:Self-reported severe/very severe VMS were associated with intermediate/high risk for OSA in midlife women, even in women with BMI <25 kg/m2. Given the limitations of the STOP-BANG tool, OSA risk may, however, have been overestimated.

SummaryThis paper is a result of work of the AES/ILAE Translational Task Force of the International League Against Epilepsy. The aim is to provide acceptable standards and interpretation of results of electrophysiological depth recordings in vivo in control rodents.