Sleep disturbance impaired memory consolidation via lateralized disruption of metabolite in the thalamus and hippocampus: A cross-sectional proton magnetic resonance spectroscopy study

Background Memory consolidation in sleep-dependent individuals involves the circuitry connections of cortex, thalamus and hippocampus, regulating via neural metabolites. However, the disruption of metabolic pattern in thalamus and hippocampus remains unclear. Objective We aim to explore the disruptive effects of insomnia on the metabolites during memory consolidation, particularly the underlying neurometabolic mechanisms in comorbidity of failed memory consolidation. Methods This study integrates clinical research with animal experiment. In clinical research, 49 participants were divided into four groups: healthy controls (HC, n = 11), insomnia with normal cognition (IS, n = 14), mild cognitive impairment without insomnia (MCI, n = 10), and insomnia with mild cognitive impairment (IS-MCI, n = 14). Magnetic resonance spectroscopy (MRS) was used to evaluate the neural γ-aminobutyric acid (GABA) and glutamate–glutamine (Glx) in bilateral thalamus. In experimental studies, the rat model of sleep deprivation combined with amyloid-β (Aβ) injection was established, after behavior testing, the levels of Glx, choline (Cho) and N-acetyl aspartate (NAA) in the bilateral hippocampus were evaluated with MRS. Results The patients in the IS-MCI group exhibited significantly lower GABA level than IS, MCI and HC groups. Results from rat studies showed that sleep deprivation exacerbated asymmetric alterations in Aβ-induced bilateral hippocampal metabolite abnormalities, which correlated with cognition. These neuro-metabolite disruption accompanied with synaptic loss and activation of astrocytes. Conclusions The lateralized decrease in GABA levels of thalamus and NAA, Cho, and Glx levels of hippocampus under conditions of sleep disturbance with cognitive decline may provide evidence for the neural metabolic mechanisms underlying the disruption of memory consolidation.