Daru. 2026 Sep 7;34(2):72. doi: 10.1007/s40199-026-00658-2.
ABSTRACT
BACKGROUND: Early postnatal GABAergic signaling is crucial for brain development and circuit formation. While Gamma-aminobutyric acid (GABA) regulates sleep-wake cycles, sleep deprivation causes cognitive impairment and oxidative stress. Although blocking GABA-A receptors has been shown to improve cognition, the effect of such blockade during development on sleep-loss-induced cognitive deficits remains unknown.
OBJECTIVES: Accordingly, this study was designed to investigate the effects of early-life inhibition of GABA-A receptors on sleep deprivation-induced cognitive impairments in adulthood.
METHODS: Thirty-two male neonatal rats were randomly assigned to four equal-sized groups (n = 8/group): Control, Bicuculline (300 µg/kg subcutaneously on postnatal days 7, 9, and 11), Sleep Deprivation (24-h SD at postnatal days (PNDs) 60-70), and Bicuculline + SD. In young adulthood (PNDs 60-70), anxiety-like behavior was assessed using the Elevated plus maze (EPM), while the Morris water maze (MWM) was used to evaluate spatial learning and memory. We then measured superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities, as well as malondialdehyde (MDA) levels in hippocampal tissue.
RESULTS: SD alone significantly increased anxiety-like behaviors, impaired spatial learning and short-term memory, reduced hippocampal SOD and GPx activities, and elevated MDA. Remarkably, early-life bicuculline pretreatment prevented SD-induced cognitive deficits, attenuated anxiety-like responses, and restored antioxidant enzyme activities while normalizing MDA levels.
CONCLUSION: Early postnatal transient blockade of GABA-A receptors was associated with decreased vulnerability to cognitive deficits, anxiety-like behaviors, and oxidative stress induced by acute sleep deprivation in adulthood. This reveals a novel developmental role of early GABAergic signaling in defense against sleep loss-induced neuropsychiatric and cognitive deficits.
PMID:42704577 | DOI:10.1007/s40199-026-00658-2
