Prenatal sleep restriction altered learning ability and memory behaviour by decreasing hippocampal synaptic plasticity in offspring mice

Inadequate sleep during pregnancy can have profound effects on offspring neurodevelopment, particularly on learning and memory abilities. This study explored whether prenatal sleep restriction (SR) induces learning and memory impairment in offspring by affecting neural plasticity in the hippocampus using four groups of pregnant mice: short-sleep-restriction (S-SR, 4 h), mid-sleep-restriction (M-SR, 10 h), long-sleep-restriction (L-SR, 18 h), and a control group without SR. SR was implemented from gestation day 8 until delivery. Changes in adult offspring and fetal hippocampal synapse structures were observed and synapse-synthesis-related protein (BDNF and Syt7) levels were measured to establish changes indicative of neurodevelopmental impairment. Offspring learning and memory abilities were further evaluated using Morris water maze test, passive avoidance test, and open field test from postnatal day 35. The findings revealed significant declines in spatial learning and memory across all SR groups. Additionally, adult offspring exhibited reduced hippocampal synapse numbers, thinner postsynaptic densities in S-SR and MSR groups, and widened synaptic clefts in the L-SR group. Synapse-synthesis-related proteins, including brain-derived neurotrophic factor (BDNF) and synaptotagmin-7 (Syt7), showed decreased expression in the hippo-campus of offspring mice in all SR groups, with BDNF expression also reduced in fetal hippocampi. Moreover, BDNF methylation levels indicated significant decreases in BDNF_3 and increases in BDNF_5 specifically in the S-SR group. Notably, prenatal S-SR induced more pronounced impairments in offspring learning and memory compared to L-SR. These findings underscore how prenatal SR disrupts fetal neurodevelopment, emphasizing hippocampal synaptic plasticity as a critical mechanism contributing to impaired cognitive function in offspring. This can help with risk identification and early intervention.