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REM Sleep Deprivation The Complex Research Proposal

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[Pedrazzoli et.al, 2004] While the above study discussed changes in levels of beta-adrenergic receptors, a research by Hip lide et.al studied the effects of REM deprivation on the binding changes among ?1-, ?2-, ?1- and ?2 adrenergic receptors in different regions of the brain. All the 91 rats used in the study were sleep deprived for 96 hours prior to the experiment. It was observed that the binding of [3H] prazosin to the ?1 receptors was not considerably different along the different regions of the brain but a mild reduction was observed. Similarly there was no significant difference in the binding to ?2 sites labeled as [3H] UK-14, 314 in all of the 91 observed areas but it showed a mild increase. However, the ?1- and ?2 receptors showed considerable reduction in binding. Data gathered using quantitative receptor autoradiography revealed that atleast in 13 of 69 brain regions, ?1 receptor binding was considerably reduced while similar reductions for ?2 receptor binding was observed in 25 of the 72 regions. This experiment confirms that norepinephrine receptors are affected by REM deprivation. [Hip lide et.al, 1998]

Yan et.al (2007) studied the effects of prolonged sleep deprivation on the synaptic plasticity of mouse hypocretin and orexin neurons. The researches used the drug modafinil (used in treatment for narcolepsy) to prolong wakefulness in the mice. It was observed that the induced wakefulness created long-term potentiation of the glutamatergic synapses of the hypcretin and orexin neurons in the lateral hypothalamus known as the homeostatis center. This increased activity of the glutamatergic synapses is evident from the mEPSCs recordings obtained at 0, 1, 2 hours after the injecting with modafinil. The frequencies of mEPSC recordings obtained after 1 hour was 9.08 ± 1.56 Hz while it was 5.54 ± 0.70 Hz (n = 17) in the control mice. The mEPSC frequencies after 2 hours were 7.84 ± 0.72 Hz (n = 29) in the experimental mice and 5.91 ± 0.58 Hz (n = 29) in the control group. Similar long-term potentiation of the glutamatergic synapses was observed when sleep deprivation was caused by gentle handling instead of using modafinil. This study clearly shows that sleep deprivation causes changes in the excitatory synapses and that...

[Yan Et.al, 2007]
Conclusion

Sleep is a biological process shared by all living beings and it plays a very critical role in maintaining the overall health of the body. The complex neurochemistry of the sleep wake cycle has been researched much over the last few decades. When REM sleep is disturbed, the brain cellular machinery triggers various neurobiological responses involving selective expression of genes, down regulation and upregulation of neurotransmitters, as well as reorganization of excitatory synapses. The levels of neurotransmitters like norephinephirine, GABA and acetylcholine and alterations in the binding to the receptors are clearly evidenced during induced REM deprivation. Some of the studies discussed above also showed REM sleep deprivation could be an useful anti-depressant therapy as many anti-depressant drugs elicit similar molecular mechanisms as induced by REM deprivation. If prolonged REM deprivation can cause oxidative stress leading to neuronal damage.

Bibliography

1-Majumdar S, Mallick BN. 'Cytomorphometric changes in rat brain neurons after rapid eye movement sleep deprivation' Neuroscience. 2005;135(3): 679-90.

2- Majumdar S, Mallick BN. 'Increased levels of tyrosine hydroxylase and glutamic acid decarboxylase in locus coeruleus neurons after rapid eye movement sleep deprivation in rats'. Neurosci Lett. 2003 Mar 6; 338(3): 193-6

3- Basheer R, Magner M, McCarley RW, Shiromani PJ. 'REM sleep deprivation increases the levels of tyrosine hydroxylases and norepinephrine transport mRNA in the locus coeruleus.' Molecular brain research, 1998, vol. 57, no2, pp. (235-240)

4- Pedrazzoli M, Benedito MA..'Rapid eye movement sleep deprivation-induced down- regulation of beta-adrenergic receptors in the rat brainstem and hippocampus' Pharmacology, biochemistry and Behavior 2004 Sep; 79(1): 31-6

Hipolide DC, Tufik S, Rayond R, Nobrega, 'Heterogeneous effects of rapid eye movement sleep deprivation on binding to alpha- and beta- adrenergic receptor subtypes in rat brain'. JN. Neuroscience. 1998 Oct; 86(3): 977-87.

6) Yan Rao1, Zhong-Wu Liu et.al, 'Prolonged wakefulness…

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Bibliography

1-Majumdar S, Mallick BN. 'Cytomorphometric changes in rat brain neurons after rapid eye movement sleep deprivation' Neuroscience. 2005;135(3): 679-90.

2- Majumdar S, Mallick BN. 'Increased levels of tyrosine hydroxylase and glutamic acid decarboxylase in locus coeruleus neurons after rapid eye movement sleep deprivation in rats'. Neurosci Lett. 2003 Mar 6; 338(3): 193-6

3- Basheer R, Magner M, McCarley RW, Shiromani PJ. 'REM sleep deprivation increases the levels of tyrosine hydroxylases and norepinephrine transport mRNA in the locus coeruleus.' Molecular brain research, 1998, vol. 57, no2, pp. (235-240)

4- Pedrazzoli M, Benedito MA..'Rapid eye movement sleep deprivation-induced down- regulation of beta-adrenergic receptors in the rat brainstem and hippocampus' Pharmacology, biochemistry and Behavior 2004 Sep; 79(1): 31-6
J. Clin. Invest. 117(12): 4022-4033 (2007). Accessed 6th Dec 2008, Available Online at, http://www.jci.org/articles/view/32829
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