Munder A. Zagaar

Exercise prevents sleep deprivation-associated anxiety-like behavior in rats: Potential role of oxidative stress mechanisms

Our previous work suggests that pharmacological induction of oxidative stress causes anxiety-like behavior in rats. Interestingly, sleep deprivation is reported to cause oxidative damage in the brain and is also reported to be anxiogenic. Minimal mechanistic insights are available. In this study, using a behavioral and biochemical approach, we investigated involvement of oxidative stress mechanisms in sleep deprivation-induced anxiety-like behavior of rats and the protective role of treadmill exercise in this process. We report that acute sleep deprivation (SD) increases oxidative stress in the cortex, hippocampus and amygdala while prior treadmill exercise prevents this increase. Serum corticosterones also increase with SD but its levels are normalized in exercised sleep-deprived rats. Also, anxiety-like behavior of rats significantly increases with SD while prior treadmill exercise prevents this increase. Protein expression of two enzymes involved in antioxidant defense, glyoxalase (GLO)-1 and glutathione reductase (GSR)-1 increased after 24h SD in the hippocampus, cortex and amygdala while their levels were normalized in exercised sleep-deprived rats. It is plausible that oxidative stress via regulation of GLO1 and GSR1 is involved in sleep deprivation-induced anxiety-like behavior of rats.

Treadmill Exercise Prevents Learning and Memory Impairment in Alzheimer’s Disease-Like Pathology

Alzheimers disease (AD) is a neurodegenerative disorder that is characterized by progressive memory loss. In contrast, accumulating evidence suggests a neuroprotective role of regular exercise in aging associated memory impairment. In this study, we investigated the ability of regular exercise to prevent impairments of short-term memory (STM) and early long-term potentiation (E-LTP) in area CA1 of the hippocampus in a rat model of AD (i.c.v. infusion of 250 pmol/day Aβ1-42 peptides). We utilized behavioral assessment, in vivo electrophysiological recording, and immunoblotting in 4 groups of adult Wistar rats: control, treadmill exercise (Ex), β-amyloid-infused (Aβ), and amyloid-infused/treadmill exercised (Ex/Aβ). Our findings indicated that Aβ rats made significantly more errors in the radial arm water maze (RAWM) compared to all other groups and exhibited suppressed E-LTP in area CA1, which correlated with deleterious alterations in the levels of memory and E-LTP-related signaling molecules including calcineurin (PP2B), brain derivedneurotrophic factor (BDNF) and phosphorylated CaMKII (p-CaMKII). Compared to controls, Ex and Ex/Aβ rats showed a similar behavioral performance and a normal E-LTP with no detrimental changes in the levels of PP2B, BDNF, and p- CaMKII. We conclude that treadmill exercise maybe able to prevent cognitive impairment associated with AD pathology.

Neurobiological Consequences of Sleep Deprivation

Although the physiological function of sleep is not completely understood, it is well documented that it contributes significantly to the process of learning and memory. Ample evidence suggests that adequate sleep is essential for fostering connections among neuronal networks for memory consolidation in the hippocampus. Sleep deprivation studies are extremely valuable in understanding why we sleep and what are the consequences of sleep loss. Experimental sleep deprivation in animals allows us to gain insight into the mechanism of sleep at levels not possible to study in human subjects. Many useful approaches have been utilized to evaluate the effect of sleep loss on cognitive function, each with relative advantages and disadvantages. In this review we discuss sleep and the detrimental effects of sleep deprivation mostly in experimental animals. The negative effects of sleep deprivation on various aspects of brain function including learning and memory, synaptic plasticity and the state of cognition-related signaling molecules are discussed.

Regular Exercise Prevents Sleep Deprivation Associated Impairment of Long-Term Memory and Synaptic Plasticity in The CA1 Area of the Hippocampus

STUDY OBJECTIVES The present study aimed to investigate the effects of treadmill exercise on sleep deprivation (S-D)-induced impairment of hippocampal dependent long-term memory, late phase long-term potentiation (L-LTP) and its signaling cascade in the cornu ammonis 1 (CA1) area. EXPERIMENTAL DESIGN Animals were conditioned to run on treadmills for 4 weeks then deprived of sleep for 24 h using the columns-in-water method. We tested the effect of exercise and/or S-D on behavioral performance using a post-learning paradigm in the radial arm water maze (RAWM) and in vivo extracellular recording in the CA1 area. The levels of L-LTP-related molecules in the CA1 area were then assessed both before and after L-LTP induction. MEASUREMENTS AND RESULTS After 24 h of S-D, spatial long-term memory impairment in the RAWM and L-LTP suppression was prevented by 4 weeks of regular exercise. Regular exercise also restored the S-D-associated decreases in the basal levels of key signaling molecules such as: calcium/calmodulin kinase IV (CaMKIV), mitogen-activated protein kinase (MAPK/ERK), phosphorylated cAMP response element-binding protein (P-CREB) and brain derived neurotrophic factor (BDNF), in the CA1 area. After L-LTP induction, regular exercise also prevented the S-D-induced down regulation of BDNF and P-CREB protein levels. CONCLUSIONS The results suggest that our exercise protocol may prevent 24-h S-D-induced impairments in long-term memory and LTP by preventing deleterious changes in the basal and post-stimulation levels of P-CREB and BDNF associated with S-D.

Regular treadmill exercise prevents sleep deprivation-induced disruption of synaptic plasticity and associated signaling cascade in the dentate gyrus.

STUDY OBJECTIVES Evidence suggests that regular exercise can protect against learning and memory impairment in the presence of insults such as sleep deprivation. The dentate gyrus (DG) area of the hippocampus is a key staging area for learning and memory processes and is particularly sensitive to sleep deprivation. The purpose of this study was to determine the effect of regular exercise on early-phase long-term potentiation (E-LTP) and its signaling cascade in the presence of sleep deprivation. EXPERIMENTAL DESIGN Rats were exposed to 4 weeks of regular treadmill exercise then subsequently sleep-deprived for 24h using the modified multiple platform model before experimentation. We tested the effects of exercise and/or sleep deprivation using electrophysiological recording in the DG to measure synaptic plasticity; and Western blot analysis to quantify the levels of key signaling proteins related to E-LTP. MEASUREMENTS AND RESULTS Regular exercise prevented the sleep deprivation-induced impairment of E-LTP in the DG area as well as the sleep deprivation-associated decrease in basal protein levels of phosphorylated and total α calcium/calmodulin-dependent protein kinase II (P/total-CaMKII) and brain-derived neurotrophic factor (BDNF). High frequency stimulation (HFS) to the DG area was used to model learning stimuli and increased the P-CaMKII and BDNF levels in normal animals: yet failed to change these levels in sleep-deprived rats. However, HFS in control and sleep-deprived rats increased the levels of the phosphatase calcineurin. In contrast, exercise increased BDNF and P-CaMKII levels in exercised/sleep-deprived rats. CONCLUSIONS Regular exercise appears to exert a protective effect against sleep deprivation-induced spatial memory impairment by inducing hippocampal signaling cascades that positively modulate basal and stimulated levels of key effectors such as P-CaMKII and BDNF, while attenuating increases in the protein phosphatase calcineurin.

Regular exercise prevents non-cognitive disturbances in a rat model of Alzheimer's disease.

Previously, we reported that in a rat model of sporadic Alzheimers disease (AD) generated by exogenous administration of Aβ₁₋₄₂ (250 pmol/d for 2 wk) via mini-osmotic pump, the animals exhibited learning and memory impairment, which could be attributed to the deleterious alterations in the levels of cognition-related signalling molecules. We showed that 4 wk of treadmill exercise totally prevented these impairments. Here, we evaluated the effect of exercise on non-cognitive function and basal synaptic transmission in the Cornu Ammonis 1 (CA1) area using the same AD model. Our results indicated that the anxiety behaviour of Aβ-treated rats was prevented by 4 wk of treadmill exercise. Exercised/Aβ-infused rats spent a longer time in the centre area of the open field (OF), elevated plus maze (EPM) paradigms and the light area of the light-dark (LD) box, which were similar to those of control and exercise rats. Furthermore, under basal conditions the aberrant up-regulation of calcineurin (PP2B) and reduction of phosphorylated Ca²⁺/calmodulin dependent protein kinase II (p-CaMKII) levels induced by AD-like pathology were normalised by the exercise regimen. We conclude that regular exercise may exert beneficial effects on both cognitive and non-cognitive functions in this AD model.

Corrigendum to “Regular treadmill exercise prevents sleep deprivation-induced disruption of synaptic plasticity and associated signaling cascade in the dentate gyrus” [Mol. Cell Neurosci. 56 (2013 Sep) 375–83]

Corrigendum to “Regular treadmill exercise prevents sleep deprivationinduced disruption of synaptic plasticity and associated signaling cascade in the dentate gyrus” [Mol. Cell Neurosci. 56 (2013 Sep) 375–83] M. Zagaara,, A. Dao, I. Alhaider, K. Alkadhi a Department of Pharmacological and Pharmaceutical Sciences, University of Houston, TX, USA b College of Clinical Pharmacy, King Faisal University, Saudi Arabia

Correction to: Comparison of the Effect of Exercise on Late-Phase LTP of the Dentate Gyrus and CA1 of Alzheimer’s Disease Model

The original version of this article unfortunately does not include the second affiliating institution of Dr. Munder A. Zagaar. “Department of Pharmacy Pracce and Clinical Health Sciences, Texas Southern University, Houston, TX 77004” should have been included on the paper.

Chapter 16:Neuroprotective Effects of Caffeine in Sleep Deprivation

Sleep is a state of temporary lack of consciousness that can be interrupted by various stimuli. Although the function of sleep is not well understood, it seems to be essential for the wellbeing and survival of the organism. Prolonged sleep loss, and insufficient sleep can results in dire health cons...