ReviewSleep deprivation and hippocampal vulnerability: changes in neuronal plasticity, neurogenesis and cognitive function

- Sleep benefits neuronal plasticity and thereby supports brain function and cognition.
- Sleep deprivation impairs hippocampus-dependent learning and memory.
- Sleep deprivation impairs hippocampal cAMP-PKA signaling and gene transcription.
- Sleep deprivation reduces hippocampal neurogenesis and hippocampal volume.
- Chronic sleep disruption contributes to cognitive disorders and psychiatric diseases.

Despite the ongoing fundamental controversy about the physiological function of sleep, there is general consensus that sleep benefits neuronal plasticity, which ultimately supports brain function and cognition. In agreement with this are numerous studies showing that sleep deprivation (SD) results in learning and memory impairments. Interestingly, such impairments appear to occur particularly when these learning and memory processes require the hippocampus, suggesting that this brain region may be particularly sensitive to the consequences of sleep loss. Although the molecular mechanisms underlying sleep and memory formation remain to be investigated, available evidence suggests that SD may impair hippocampal neuronal plasticity and memory processes by attenuating intracellular cyclic adenosine monophosphate (cAMP)-protein kinase A (PKA) signaling which may lead to alterations in cAMP response element binding protein (CREB)-mediated gene transcription, neurotrophic signaling, and glutamate receptor expression. When restricted sleep becomes a chronic condition, it causes a reduction of hippocampal cell proliferation and neurogenesis, which may eventually lead to a reduction in hippocampal volume. Ultimately, by impairing hippocampal plasticity and function, chronically restricted and disrupted sleep contributes to cognitive disorders and psychiatric diseases.