Ramli, Norhida
(2021)
The effects of sleep deprivation on spatial memory, dream and hyperphosphorylated tau proteins expression in rats.
PhD thesis, Universiti Sains Malaysia.
Abstract
Circadian rhythm is regulated by an endogenous biological regulator
controlling various physiological activities, including cell cycle, body temperature,
and metabolism. Some consolidation of memory occurs during Rapid Eye Movement
(REM) sleep, so when the circadian system breaks down and REM sleep depressed,
the memory will be affected. Downstream regulatory modulator antagonist (DREAM)
proteins were discovered to affects learning and memory, while Tau protein
hyperphosphorylation indicates some degree of neuronal instability influencing
learning processes. This study aimed to examine the effects of sleep and circadian
disruption (CD) on memory. One hundred and fourty four Sprague Dawley rats were
used in this study. In the CD experiment, acute circadian disruption (ACD) was
induced by putting the rats on a three-hour phase advance method for 6 days followed
by 10 days of re-entrainment. This cycle was induced four times in a chronic circadian
disruption (CHCD) study. On the other hand, REM sleep deprivation was induced by
putting the rats on a small platform in a water tank (REMsd group). The REMsd
control group (PC) was placed in the same condition as the REMsd group except that
they were put in a broader platform to sleep and relax (PC group). The free-moving
control group (CC) was placed in normal propylene cages (CC group). It was followed
by the Morris water maze (MWM) task to assess spatial, probe test, and reverse spatial
test. Then, the rat’s brain from the hippocampal region was removed. The neuron's
nucleus and cytoplasm were extracted for DREAM, normal Tau, and phosphorylated
Tau protein expression analyses by Immunohistochemistry and Western Blot (WB)
analysis. In MWM test, the mean daily escape latency was measured for all rats from
each group. The differences of EL between the groups were not statistically significant
(p > 0.05) when compared between all groups in REM and CD experimental groups.
The probe test showed no statistically significant (p>0.05) difference between the
groups in the REMsd and CD experiment. The reverse spatial trial showed no
significant difference between all groups (p>0.05) in the REMsd and CD experiment.
DREAM protein expression was not statistically significant difference between groups
in the REMsd and CD experiment. Tau and phosphorylated Tau protein was found to
be significantly different when compared between REMsd and CC groups (p<0.05)
and ACD and CCD group in the REMsd and CD experiment, but not significant
difference for hyperphosphorylated Tau protein expression. WB analysis showed that
the mean relative DREAM protein level was not statistically significant between all
groups in the REMsd and CD experiment groups. The mean relative
hyperphosphorylated Tau difference also was found not statistically significant
between groups in the REMsd and CD experiments. In conclusion, the current study
protocol failed to adequately elicited significant changes in neurobehavioral and level
of the DREAM and hyperphosphorylated Tau protein expression.
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