Vulnerability of Left Amygdala to Total Sleep Deprivation and Reversed Circadian Rhythm in Molecular Level: Glut1 as a Metabolic Biomarker

  • Parastou Kordestani Moghadam Institute for Cognitive Science Studies (ICSS), Tehran, Iran
  • Mohammad Nasehi 1.Institute for Cognitive Science Studies (ICSS), Tehran, Iran 2.Cognitive and Neuroscience Research Center (CNRC), Tehran Medical Sciences Branch, Islamic Azad University, Tehran, Iran
  • Fariba Khodagholi Neuroscience Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
  • Mohamad Reza Zarrindast 1.Institute for Cognitive Science Studies (ICSS), Tehran, Iran 2.Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
Keywords: Sleep, Circadian Rhythm, Glucose Transport Protein, Amygdala


Background: Sleep deprivation (SD) in the long term can cause multi-organ dysfunction as well as neurocognitive disorders. Daytime sleep or napping is a biological compensate due to insomnia or sleep deprivation. Metabolic responses to this biological rhythm may being as a biological indicator or biomarker to compare the effect of them. Glucose transporter type 1 (Glut-1) is one of the metabolic biomarkers that is affected by several conditions such as stress, seizure, malignancy, and neurocognitive disorders. We studied the effect of SD, circadian reversed (R) and napping models on the Glut-1 expression level in the right and left amygdala. Materials and Methods: Sixty-four Wistar rats were divided into eight groups as follow: Intact group that rats were placed in a cage without any intervention. In the sham group, rats were on the stable pedal of the SD apparatus (turn off). Experimental groups include total SD48, total SD48- (plus short nap), total SD48+ (plus long nap), R48, R48- (plus short nap), and R48+ (plus long nap).The Glut-1 expression level in the right and left amygdala were measured by western blotting. Results: Our findings demonstrated the significant effect of both SD for 48 hours and reversed circadian on the expression of Glut-1 from sham and intact groups. The long nap plus them could decrease the elevation of Glut-1 in the left amygdala. However, the short nap could not reduce this elevation of Glut-1. Conclusion: Left amygdala is vulnerable to the fluctuation of hypothalamic-pituitary-adrenal axis and stress. In other words, sleep disorders are affecting by Glut-1 as a metabolic biomarker in left amygdala alone. [GMJ.2019;8:e970] 


McEwen BS. Sleep deprivation as a neurobiologic and physiologic stressor: allostasis and allostatic load. Metabolism. 2006;55:S20-S3.


Altevogt BM, Colten HR. Sleep disorders and sleep deprivation: an unmet public health problem. National Academies Press; 2006.


Palmer CA, Alfano CA. Sleep Architecture Relates to Daytime Affect and Somatic Complaints in Clinically Anxious but Not Healthy Children. Journal of Clinical Child & Adolescent Psychology. 2017;46(2):175-87.


Payne JD, Kensinger EA. Sleep leads to changes in the emotional memory trace: evidence from FMRI. Journal of Cognitive Neuroscience. 2011;23(6):1285-97.


Payne JD, Stickgold R, Swanberg K, Kensinger EA. Sleep preferentially enhances memory for emotional components of scenes. Psychological Science. 2008;19(8):781-8.

PMid:18816285 PMCid:PMC5846336

Rasch B, Born J. Maintaining memories by reactivation. Current opinion in neurobiology. 2007;17(6):698-703.


Smith C. Sleep states and memory processes. Behavioural brain research. 1995;69(1):137-45.

Stickgold R. Sleep-dependent memory consolidation. Nature. 2005;437(7063):1272.


Walker MP, Stickgold R. Sleep, memory, and plasticity. Annu Rev Psychol. 2006;57:139-66.


Tucker MA, Hirota Y, Wamsley EJ, Lau H, Chaklader A, Fishbein W. A daytime nap containing solely non-REM sleep enhances declarative but not procedural memory. Neurobiology of learning and memory. 2006;86(2):241-7.


Wulff K, Gatti S, Wettstein JG, Foster RG. Sleep and circadian rhythm disruption in psychiatric and neurodegenerative disease. Nature reviews Neuroscience. 2010;11(8):589.


Åkerstedt T, Torsvall L. Napping in shift work. Sleep. 1985;8(2):105-9.


Watamura SE, Donzella B, Kertes DA, Gunnar MR. Developmental changes in baseline cortisol activity in early childhood: Relations with napping and effortful control. Developmental Psychobiology. 2004;45(3):125-33.


Takahashi M. The role of prescribed napping in sleep medicine. Sleep medicine reviews. 2003;7(3):227-35.


Walker MP, van Der Helm E. Overnight therapy? The role of sleep in emotional brain processing. Psychological bulletin. 2009;135(5):731.

PMid:19702380 PMCid:PMC2890316

Marcaggi P, Attwell D. Role of glial amino acid transporters in synaptic transmission and brain energetics. Glia. 2004;47(3):217-25.


Sofroniew MV. Molecular dissection of reactive astrogliosis and glial scar formation. Trends in neurosciences. 2009;32(12):638-47.

PMid:19782411 PMCid:PMC2787735

Sofroniew MV, Vinters HV. Astrocytes: biology and pathology. Acta neuropathologica. 2010;119(1):7-35.

PMid:20012068 PMCid:PMC2799634

Morales I, Rodriguez M. Self‐induced accumulation of glutamate in striatal astrocytes and basal ganglia excitotoxicity. Glia. 2012;60(10):1481-94.


Featherstone DE. Intercellular glutamate signaling in the nervous system and beyond. ACS chemical neuroscience. 2009;1(1):4-12.

PMid:22778802 PMCid:PMC3368625

Darby M, Kuzmiski JB, Panenka W, Feighan D, MacVicar BA. ATP released from astrocytes during swelling activates chloride channels. Journal of neurophysiology. 2003;89(4):1870-7.


Starkov AA, Fiskum G, Chinopoulos C, Lorenzo BJ, Browne SE, Patel MS et al. Mitochondrial α-ketoglutarate dehydrogenase complex generates reactive oxygen species. Journal of Neuroscience. 2004;24(36):7779-88.


Tretter L, Adam-Vizi V. Alpha-ketoglutarate dehydrogenase: a target and generator of oxidative stress. Philosophical Transactions of the Royal Society of London B: Biological Sciences. 2005;360(1464):2335-45.

PMid:16321804 PMCid:PMC1569585

Falkowska A, Gutowska I, Goschorska M, Nowacki P, Chlubek D, Baranowska-Bosiacka I. Energy metabolism of the brain, including the cooperation between astrocytes and neurons, especially in the context of glycogen metabolism. International journal of molecular sciences. 2015;16(11):25959-81.

PMid:26528968 PMCid:PMC4661798

Young CD, Lewis AS, Rudolph MC, Ruehle MD, Jackman MR, Yun UJ et al. Modulation of glucose transporter 1 (GLUT1) expression levels alters mouse mammary tumor cell growth in vitro and in vivo. PloS one. 2011;6(8):e23205.

PMid:21826239 PMCid:PMC3149640

Detka J, Kurek A, Basta-Kaim A, Kubera M, Lasoń W, Budziszewska B. Elevated brain glucose and glycogen concentrations in an animal model of depression. Neuroendocrinology. 2014;100(2-3):178-90.


Weber Y, Kamm C, Suls A, Kempfle J, Kotschet K, Schüle R et al. Paroxysmal choreoathetosis/spasticity (DYT9) is caused by a GLUT1 defect. Neurology. 2011;77(10):959-64.


Meerlo P, Sgoifo A, Suchecki D. Restricted and disrupted sleep: effects on autonomic function, neuroendocrine stress systems and stress responsivity. Sleep medicine reviews. 2008;12(3):197-210.


Norozpour Y, Nasehi M, Sabouri-Khanghah V, Torabi-Nami M, Zarrindast M-R. The effect of CA1 α2 adrenergic receptors on memory retention deficit induced by total sleep deprivation and the reversal of circadian rhythm in a rat model. Neurobiology of learning and memory. 2016;133:53-60.


Bradford MM. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Analytical biochemistry. 1976;72(1-2):248-54.

Drevets WC, Price JL, Furey ML. Brain structural and functional abnormalities in mood disorders: implications for neurocircuitry models of depression. Brain structure and function. 2008;213(1-2):93-118.

PMid:18704495 PMCid:PMC2522333

LeDoux J. The emotional brain, fear, and the amygdala. Cellular and molecular neurobiology. 2003;23(4-5):727-38.


Tamaki M, Bang JW, Watanabe T, Sasaki Y. Night watch in one brain hemisphere during sleep associated with the first-night effect in humans. Current biology. 2016;26(9):1190-4.

PMid:27112296 PMCid:PMC4864126

Ocklenburg S, Korte SM, Peterburs J, Wolf OT, Güntürkün O. Stress and laterality–The comparative perspective. Physiology & behavior. 2016;164:321-9.


How to Cite
Kordestani Moghadam, P., Nasehi, M., Khodagholi, F., & Zarrindast, M. R. (2019). Vulnerability of Left Amygdala to Total Sleep Deprivation and Reversed Circadian Rhythm in Molecular Level: Glut1 as a Metabolic Biomarker. Galen Medical Journal, 8, e970.
Original Article