Rapid Eye Movement Sleep Loss

Link

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=16887278&query_hl=1&itool=pubmed_docsum

Background

Rapid  eye movement or REM is a component of sleep that  is necessary for normal function.  Loss of REM or REM deprivation (REMD) has several detrimental physiological and behavior consequences. These include affects on brain maturation and development and brain connectivity REMD is found in a number of neurodegenerative diseases including Parkinson’s disease. At the cellular level, alterations in neuronal activity, membrane fluidity, calcium channel function, and Na+-K+ ATPase have been described.  Additionally, the integrity and survival of neurons may be compromised.

Hypothesis

The authors hypothesized that since REMD affects functions that are necessary for neuronal well being that REMD would affect the underlying process involved in maintaining survival. This study evaluated the effects of REMD and recovery in male Wistar rats on markers of cellular degeneration (bcl-2, bax, Tunnel staining and Hoecht staining) and the cytoskeleton components actin and tubulin in brain regions associated with the generation of REM.

Methods

1. Adult male Wistar rats were exposed to one of four conditions: controls left in their home cage (FMC), REMD rats placed on a small platform for 6 days surrounded by water (REMD), rats placed on a larger platform surrounded by water for 4, 6 and 10 days (LPC) and a recovery group that was REMD for 6 days and then allowed to recover for 3 days in their home cage (REC).
2. Rats were anesthetized with an IP injection of sodium pentobarbital, perused transcardially with phosphate buffer, and then with fixatives for either light microscopy or electron microscopy. Frozen brain sections were taken from 2 pontine regions (locus coeruleus (LC) and the laterodorsal tegmentum/pedunculoponine tegmentum (LDT/PPT)) and from 2 hypothalamic regions (medial preoptic nucleus (MPO) and the lateral septum (LS)).
3. For evaluating indicators of cell death and integrity immunohistochemistry was used to quantitate actin and tubulin expression, bcl-2 (anti-apoptosis) and bax (apoptosis) expression and TUNNEL and Hoechest staining. The amino cupric silver method was used to evaluate the status of individual neurons.
4. Image analysis was used to count the total number of neurons in each brain region and also to evaluate the number of neurons that showed indictors of cell death. A total of 60-80 neurons were evaluated per section, with 8-10 sections observed per brain region. There were 3 animals for each category. Data in the REMD, LPC and REC groups were “normalized” by control data in the FMC group. Statistics include one way ANOVA’s.

Results

1. REMD  for 6 and 10 days, but not 4 days caused an increase of neuronal degeneration.
2. In 6 day REMD rats all brain regions except the LS showed clear signs of neuronal degeneration, apoptosis, and decreased levels of actin and tubulin, whereas these indicators were comparable among the FMC, LPC and REC groups.

Discussion and Clinical significance

This study indicated that REMD for 6 or more days in male Wistar rats resulted in loss of neuronal integrity in several brain regions associated with sleep and waking.  The underlying mechanisms responsible for these findings need further study. Moreover, there may be different effects of REM deprivation in females. Since there are lifestyles (shift workers and residents), individuals who suffer from sleep disorders,  and patients with degenerative neural disorders (Parkinson’s disease and Alzheimer’s disease)  experience REM deprivation, this may lead to neuronal loss possibly contributing to the progression of a positive cycle leading to further neuronal decline. The functional consequences of REMD have implications on current behaviors and may have life long consequences.

References

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