Lalan Thakur

Hypobaric hypoxia modulates brain biogenic amines and disturbs sleep architecture

Sojourners to high altitude experience poor-quality of sleep due to hypobaric hypoxia (HH). Brain neurotransmitters are the key regulators of sleep wakefulness. Scientific literature has limited information on the role of brain neurotransmitters involved in sleep disturbance in HH. The present study aimed to investigate the time dependent changes in neurotransmitter levels and enzymes involved in the biosynthesis of brain neurotransmitters in frontal cortex, brain stem, cerebellum, pons and medulla and the effect of these alterations on sleep architecture in HH. Thirty adult Sprague-Dawley rats, body weight of 230-250 g were exposed to simulated altitude ∼7620 m, 282 mm Hg, partial pressure of O(2) 59 mm Hg for 7 and 14 days continuously in an animal decompression chamber. After 7 and 14 days of HH, brain nor-epinephrine and dopamine levels were significantly increased in frontal cortex, brain stem, cerebellum and pons and medulla whereas serotonin level was significantly reduced in frontal cortex and pons and medulla after 14 days of HH. Tyrosine hydroxylase level in locus coeruleus (LC) was significantly increased whereas Choline Acetyl Transferase and Glutamic Acid Decarboxylase (GAD) levels were significantly reduced in laterodorsal-tegmentum and pedunculopontine-tegmentum after 7 days of HH. GAD was also reduced in LC after 7 days HH. Alteration in these neurotransmitters and enzyme levels was accompanied with reduction in quality and quantity of sleep. There was a significant increase in sleep latency, rapid eye movement (REM) latency, duration of active awake, quiet awake, quiet sleep and a significant decrease in duration of REM sleep and deep sleep on day 7 and 14 of HH. It was concluded that HH alters the expression of enzymes linked to sleep neurotransmitter synthesis pathway and subsequent loss of homeostasis at neurotransmitter level disrupts the sleep pattern in hypobaric hypoxia.

Effect of l-Carnitine Supplementation on Endurance Exercise in Normobaric/Normoxic and Hypobaric/Hypoxic Conditions

Abstract Objective.—To evaluate the effect of l-carnitine supplementation on improving endurance exercise in normobaric/normoxic and hypobaric/hypoxic environments. Methods.—Six-week–endurance-trained male Sprague-Dawley rats (n = 24) were randomly divided into 2 groups: control and experimental; the latter group was supplemented with l-carnitine, administered orally in a dose of 100 mg·kg−1 body weight. The animals were supplemented for 25 days under ambient normobaric/normoxic conditions and thereafter were exposed to 72 hours of hypobaric hypoxia equivalent to 6100 m. The supplementation was continued during the exposure. “Run to exhaustion” was recorded on day 1 (R1) (presupplementation) and on days 7 (R2), 14 (R3), 21 (R4), and 28 (R5, which followed the last 72 hours of hypoxic exposure) of supplementation. Food intake, body weight, and the biochemical measures of plasma glucose, total cholesterol, and high-density lipoprotein (HDL) cholesterol were recorded. Results.—There was a significant improvement in endurance exercise, as indicated by an increase in run to exhaustion following l-carnitine supplementation under normobaric normoxia (36%–39%) and hypobaric hypoxia (50%). l-carnitine supplementation had no effect on plasma glucose levels either at sea level or after hypoxic exposure. Total cholesterol was decreased in normoxic and HDL cholesterol was increased in normoxic and hypoxic conditions, indicating a beneficial effect of exercise. Conclusion.—l-carnitine supplementation improved exercise endurance in rats exposed to normobaric normoxic and hypobaric hypoxic conditions. Such supplementation would be beneficial in delaying the onset of fatigue during prolonged exercise in both conditions, indicating its potentially beneficial use at high altitude.

Modafinil improves event related potentials P300 and contingent negative variation after 24 h sleep deprivation

AIMS The efficacy of modafinil as a countermeasure in the reduction of cognitive decline following 24 h of sleep deprivation (SD) on subjective sleepiness scales, event-related potential (ERP) P300, and contingent negative variation (CNV) was evaluated. MAIN METHODS Eleven healthy males, age 25-30 years participated. The experiment was performed in five sessions on different days between 7 and 8a.m. Session 1, baseline recordings; Session 2, after one nights SD; Session 3, 48 h of recovery from SD; Session 4, after 1 week of Session 1, following one nights SD along with modafinil (400mg/day); Session 5, 48 h of recovery after SD+modafinil. KEY FINDINGS Subjective sleepiness scores increased significantly after SD as compared to baseline (P<0.01), but remained unaltered after modafinil supplementation. There was an increase in N100 and P300 peak latencies of ERP following SD (P<0.01), which was reduced with modafinil (P<0.05). There was an increase in CNV M100 and P300 peak latencies after SD (P<0.01) which decreased with the use of modafinil (P<0.05). The CNV reaction time increased following SD (P<0.01) and decreased with the use of modafinil (P<0.05). No significant effects on ERP N200, P200 latencies and P200, P300 amplitudes and CNV N100, M200 peak latencies and M100, M200 amplitudes were observed. SIGNIFICANCE The results strongly suggest that modafinil in a dose of 400mg/day, reduces the subjective sleepiness and cognitive decline following 24 h of SD.

Tyrosine ameliorates heat induced delay in event related potential P300 and contingent negative variation

The efficacy of tyrosine, a catecholamine precursor, as a countermeasure in the reduction of cognitive decline during heat exposure (HE) using event-related potential P300, and contingent negative variation (CNV) was evaluated. Ten healthy males, age 20-30years participated in the study. Volunteers received placebo or tyrosine (6.5g) 90min prior to HE (1.5h in 45°C+30% RH). P300 latency was significantly increased (p<0.01) during exposure with placebo, which was reduced significantly (p<0.01) after tyrosine supplementation. There was an increase in CNV M100 latency (p<0.05) and reaction time (p<0.01) and decrease in M100 amplitude (p<0.01) during HE with placebo, which returns to near normal level with the tyrosine administration. A significantly higher plasma norepinephrine (p<0.05), dopamine and epinephrine levels were detected in tyrosine supplemented group post heat exposure. HE increases the brain catecholamine activity thereby reduces the plasma norepinephrine and dopamine level leading to a reduction in cognitive performances. Tyrosine supplementation increases the catecholamine level and reduces the impairment of cognitive performance during HE.

Caffeine and Modafinil Ameliorate the Neuroinflammation and Anxious Behavior in Rats during Sleep Deprivation by Inhibiting the Microglia Activation

Background: Sleep deprivation (SD) plagues modern society due to the professional demands. It prevails in patients with mood and neuroinflammatory disorders. Although growing evidence suggests the improvement in the cognitive performance by psychostimulants during sleep-deprived conditions, the impending involved mechanism is rarely studied. Thus, we hypothesized that mood and inflammatory changes might be due to the glial cells activation induced modulation of the inflammatory cytokines during SD, which could be improved by administering psychostimulants. The present study evaluated the role of caffeine/modafinil on SD-induced behavioral and inflammatory consequences. Methods: Adult male Sprague-Dawley rats were sleep deprived for 48 h using automated SD apparatus. Caffeine (60 mg/kg/day) or modafinil (100 mg/kg/day) were administered orally to rats once every day during SD. Rats were subjected to anxious and depressive behavioral evaluation after SD. Subsequently, blood and brain were collected for biochemical, immunohistochemical and molecular studies. Results: Sleep deprived rats presented an increased number of entries and time spent in closed arms in elevated plus maze test and decreased total distance traveled in the open field (OF) test. Caffeine/modafinil treatment significantly improved these anxious consequences. However, we did not observe substantial changes in immobility and anhedonia in sleep-deprived rats. Caffeine/modafinil significantly down-regulated the pro- and up-regulated the anti-inflammatory cytokine mRNA and protein expression in the hippocampus during SD. Similar outcomes were observed in blood plasma cytokine levels. Caffeine/modafinil treatment significantly decreased the microglial immunoreactivity in DG, CA1 and CA3 regions of the hippocampus during SD, however, no significant increase in immunoreactivity of astrocytes was observed. Sholl analysis signified the improvement in the morphological alterations of astrocytes and microglia after caffeine/modafinil administration during SD. Stereological analysis demonstrated a significant improvement in the number of ionized calcium binding adapter molecule I (Iba-1) positive cells (different states) in different regions of the hippocampus after caffeine or modafinil treatment during SD without showing any significant change in total microglial cell number. Eventually, the correlation analysis displayed a positive relationship between anxiety, pro-inflammatory cytokines and activated microglial cell count during SD. Conclusion: The present study suggests the role of caffeine or modafinil in the amelioration of SD-induced inflammatory response and anxious behavior in rats. Highlights - SD induced mood alterations in rats. - Glial cells activated in association with the changes in the inflammatory cytokines. - Caffeine or modafinil improved the mood and restored inflammatory changes during SD. - SD-induced anxious behavior correlated with the inflammatory consequences.

Meditation as a Countermeasure to Reduce Cognitive Decline During Total Sleep Deprivation

Decline in cognitive functions is a major challenge for professionals during sustained wakefulness. We aimed to evaluate the efficacy of meditation as an intervention in the reduction of the cognitive decline during total sleep deprivation (TSD). Healthy male volunteers (n = 10) drawn randomly from the Indian Army participated in a 4-night study design executed before and after 2 months of meditation practice pre-intervention TSD for 24 and 36 h increased dysfunction rating score (DRS) in terms of a decline in remote and recent memory, mental balance, attention/concentration, delayed and immediate recall, verbal retention, and recognition. Visual retention remained unaltered. Stroop color-word interference (SCWI) showed a decline in ‘word’ scores after 36 h, ‘color’ score after 24 h, and ‘color-word’ score after 24 h TSD. Maze tracing test scores decreased after 24 and 36 h TSD. Post-intervention recordings of DRS no longer showed the decline in remote and recent memory, mental balance, attention/concentration, delayed and immediate recall, verbal retention, and recognition, which was seen without intervention. SCWI improved post-intervention with no significant change in ‘word’ scores and ‘color’ scores. However, ‘color-word’ scores remained low after 36 h TSD. Maze tracing test scores improved post-intervention with no significant change after 24 and 36 h TSD. After recovery sleep, there was a significant improvement in all the above measures. It was concluded that meditation could serve as an effective intervention to reduce the cognitive decline during TSD. The study substantiated the potency of meditation in reducing cognitive decline following TSD.