Mechanisms of Memory Dysfunction during High Altitude Hypoxia Training in Military Aircrew.

OBJECTIVES: Cognitive dysfunction from high altitude exposure is a major cause of civilian and military air disasters. Pilot training improves recognition of the early symptoms of altitude exposure so that countermeasures may be taken before loss of consciousness. Little is known regarding the nature of cognitive impairments manifesting within this critical window when life-saving measures may still be taken. Prior studies evaluating cognition during high altitude simulation have predominantly focused on measures of reaction time and other basic attention or motor processes. Memory encoding, retention, and retrieval represent critical cognitive functions that may be vulnerable to acute hypoxic/ischemic events and could play a major role in survival of air emergencies, yet these processes have not been studied in the context of high altitude simulation training. METHODS: In a series of experiments, military aircrew underwent neuropsychological testing before, during, and after brief (15 min) exposure to high altitude simulation (20,000 ft) in a pressure-controlled chamber. RESULTS: Acute exposure to high altitude simulation caused rapid impairment in learning and memory with relative preservation of basic visual and auditory attention. Memory dysfunction was predominantly characterized by deficiencies in memory encoding, as memory for information learned during high altitude exposure did not improve after washout at sea level. Retrieval and retention of memories learned shortly before altitude exposure were also impaired, suggesting further impairment in memory retention. CONCLUSIONS: Deficits in memory encoding and retention are rapidly induced upon exposure to high altitude, an effect that could impact life-saving situational awareness and response. (JINS, 2017, 23, 1-10).

Effects of long and short simulated flights on the saccadic eye movement velocity of aviators.

Aircrew fatigue is a major contributor to operational errors in civil and military aviation. Objective detection of pilot fatigue is thus critical to prevent aviation catastrophes. Previous work has linked fatigue to changes in oculomotor dynamics, but few studies have studied this relationship in critical safety environments. Here we measured the eye movements of US Marine Corps combat helicopter pilots before and after simulated flight missions of different durations.We found a decrease in saccadic velocities after long simulated flights compared to short simulated flights. These results suggest that saccadic velocity could serve as a biomarker of aviator fatigue.

Phenotypic profile of SWR/J and A/J mice compared to control strains: possible mechanisms underlying resistance to obesity on a high-fat diet.

To understand mechanisms underlying a resistance to obesity, two obesity-resistant inbred mouse strains, SWR/J and A/J, were compared to 3 inbred "control" strains, C3H/HeJ, BALB/cByJ and C57L/J. These 5 strains, studied at 5 weeks of age when similar in body weight, were maintained for 3 weeks on a 3-diet feeding paradigm, with separate jars of carbohydrate, protein and fat, or for 1 week on a single high-fat or low-fat diet. The control strains each chose a balanced diet, with 50% carbohydrate and 15-25% fat, and they had a similar, normal range of scores for measures of body weight, adiposity, endocrine parameters and metabolic enzyme activity. Compared to these control strains, the obesity-resistant SWR/J and A/J strains consumed more total calories and selected a diet with significantly more fat (35-45%) and less carbohydrate (35%). Despite overeating, they weighed less and had significantly reduced adiposity. They also had lower levels of insulin and exhibited increased capacity of skeletal muscle to metabolize fat, as indicated by measures beta-hydroxyacyl-CoA dehydrogenase activity or its ratio to citrate synthase. Measurements of hypothalamic peptides via radioimmunoassay or real-time quantitative PCR revealed markedly enhanced galanin (GAL) in the paraventricular nucleus and reduced neuropeptide Y (NPY) expression in the arcuate nucleus of obesity-resistant mice. These patterns in SWR/J and A/J strains, seen on a low-fat as well as high-fat diet, may reflect mechanisms involving excess GAL and reduced NPY that contribute early, respectively, to the over-consumption of a high-fat diet and a resistance to the obesity-promoting effects of this diet.

The effects of chronic ethanol consumption on energy balance in rats.

It remains unclear how ethanol truly impacts body weight and energy balance. Dietary intake studies suggest that energy intake is greater in ethanol consumers; however, large population studies have shown that ethanol intake is in fact not associated with increased body weight. Energy expenditure (EE) has been shown to be either mildly increased or unchanged after acute ethanol intake, but the effects of chronic ethanol intake on energy balance have not been well studied. The following study was performed to prospectively examine the effects of chronic moderate ethanol consumption and its interactions with the macronutrient composition of the diet on energy balance. Male Sprague-Dawley rats (n = 16) were first randomized to either a low-fat diet (LF = 10% fat, 70% carbohydrate, 20% protein) or a high-fat diet (HF = 30% fat, 50% carbohydrate, 20% protein). Rats were then randomized to receive either a 5% ethanol solution (ethanol) or water (control) as their drinking supply (day 14) for a total of 4 groups (LF-ethanol, LF-control, HF-ethanol, HF-control; n = 4 per group). On days 7, 21, and 42, indirect calorimetry was performed. Body weight and energy intake were measured throughout the study period. The rate of weight gain was unaffected by ethanol but was increased on the HF diet. Ethanol intake averaged 14.56% +/- 1.16% of total caloric intake. Both ethanol groups compensated for added ethanol calories by reducing their intake of diet, so that total energy intake was similar in all groups. As expected, respiratory quotient decreased in both ethanol groups (LF: 0.92 to 0.88; HF: 0.88 to 0.86; P <.05). However, EE was not affected by ethanol intake. These findings demonstrate that male Sprague-Dawley rats fully compensate for the calories associated with moderate chronic ethanol consumption and maintain energy balance regardless of the fat content of the baseline diet. This compensation suggests that ethanol calories are sensed, producing an appropriate reduction in the intake of other nutrients, and/or that ethanol impacts the regulation of dietary intake mediators.

Acute high-fat diet paradigms link galanin to triglycerides and their transport and metabolism in muscle.

To compare the effects of acute exposure to dietary fat to those of chronic exposure, Sprague-Dawley rats were given a high-fat diet (50% fat) or moderate-fat diet (25% fat) for 1 day, 2 h or 3 weeks. With measurements of various parameters, the high-fat diet for 21 days produced the expected changes of: (1) a significant increase in total caloric intake and dissected fat pad weights; (2) a rise in leptin and the metabolites, triglycerides (TG), non-esterified fatty acids and glucose; (3) an increase in muscle beta-hydroxyacyl-CoA dehydrogenase (HADH) and adipose lipoprotein lipase (aLPL) activity, along with a decrease in LPL activity in muscle (mLPL); and (4) elevated galanin (GAL) expression and peptide levels in the anterior region of the paraventricular nucleus (PVN), with no change in the arcuate nucleus. The acute 1-day or 2-h high-fat diet similarly increased circulating lipids, HADH activity and PVN GAL mRNA but stimulated rather than suppressed mLPL activity. These effects occurred in the absence of a change in total caloric intake, fat pad weights, and adipose-related measures, suggesting that they resulted more from the rise in dietary fat from 25% to 50% than from increased adiposity or hyperphagia. Moreover, PVN GAL mRNA in the different groups was consistently and positively correlated with the specific measures of TG levels and both HADH and mLPL activity, linking it to metabolic processes related to the transport and capacity for oxidation of TG in muscle, rather than adipose tissue.