Page 177 - Biobehavioral Resilence to Stress

154 Biobehavioral Resilience to Stress

perturbations in normal sleep–wake cycles. At times, these effects can be

specific to single mutations. For example, Shaw, Cirelli, Greenspan, and
Tononi (2000) found that compared to “wild-type” normal controls, fruit

flies with a homozygous mutation for the enzyme arylalkyamine N-acetyl
transferase responded atypically to a sleep deprivation paradigm. When
deprived of sleep for 12 h and then allowed unlimited recovery sleep, the
mutant flies demonstrated significantly greater rebound sleep than controls

and the size of this effect was dependent upon the severity of the mutation.

Franken, Chollet, and Tafti (2001) studied several strains of inbred mice

and observed that differences in recovery sleep (amount of delta power
in non-REM sleep) differed among the strains, leading the researchers to

conclude that genetic factors influence the rate at which the need for sleep

accumulates over time.
Normal sleep patterns may also depend in part upon biochemical
pathways that involve cellular messengers such as immediate-early genes.
Shiromani et al. (2000) studied two of these genes (c-fos and fos B) in mice
and explored the effects of their deletion on sleep. Depending on which gene

was deleted, there occurred changes in REM sleep with no change in wake-
fulness or slow-wave sleep ( fos B), or a selective reduction in slow-wave sleep

with increased wakefulness (c-fos). The researchers concluded that the induc-
tion of these genes in normal mice is important to coding for events critical
to sleep regulation and wakefulness.
As noted above, the enzyme arylalkyamine N-acetyl transferase is
associated with responses to sleep deprivation. The greater the period of

sleep deprivation, the greater is the expression of this enzyme. Similarly,
Cirelli, and Tononi (2000) found that induction of another enzyme (arylsul-
fotransferase [AST]) in rats was proportional to the amount of sleep depri-
vation. Both arylalkyamine N-acetyl transferase and AST are involved in
the metabolic destruction of neurotransmitters such as NE, dopamine, and
possibly serotonin. Since the genes that control production of the enzymes
are also induced in response to prolonged wakefulness, Cirelli (2002) sug-
gests that their function may be to counter or interrupt the continuous
activity of brain catecholaminergic systems during prolonged wakefulness.
That is, arylalkyamine N-acetyl transferase and AST levels may be one of

the controlling mechanisms of homeostatic processes that regulate sleep
and wakefulness. A more thorough understanding of these mechanisms
may lead to a refined assessment of individual susceptibility to the eff ects of

sleep deprivation. Such knowledge would enable individuals to be aware of
their limitations, understand the implications, and develop eff ective coun-

termeasures or strategies to avoid difficulties. In addition, pharmacological

countermeasures could be tailored to specific enzyme pathways instead of
“flogging the system” with the sort of multidimensional stimulants that are

currently available.

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