Chronic Sleep Deprivation-Induced
Proteome Changes
in Astrocytes of the Rat Hypothalamus
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Abstract
Sleep deprivation (SD) can influence
cognition, memory, and sleep/wake
homeostasis and can cause impairments in many physiological processes.
Because the homeostatic control of the sleep/wake cycle is closely
associated with the hypothalamus, the current study was undertaken
to examine proteomic changes occurring in hypothalamic astrocytes
following chronic partial SD. After chronic partial SD for 7 days,
astrocytes were prepared from rat hypothalamus using a Percoll gradient
method, and their proteome profiles were determined by LC–MS/MS.
Comparisons of the proteome profiles of hypothalamic astrocytes revealed
that chronic partial SD increased (≥1.5-fold) 89 proteins and
decreased (≤0.7-fold) 50 proteins; these changes in protein
expression were validated by western blot or immunohistochemistry.
DAVID and IPA analyses of these proteins suggested that SD may influence
gliotransmission and astrocyte activation. PPP2R1A, RTN4, VAMP-2,
LGI-1, and SLC17A7 were identified and validated as the main targets
of SD in astrocytes. Our results suggest that SD may modulate gliotransmission
in the hypothalamus, thereby disturbing sleep/wake homeostasis and
increasing susceptibility to neurological disease; however, further
studies are required to confirm whether the proteome changes are specific
to SD