ScopeA high salt (HS) diet is detrimental to cognitive function, in addition to having a role in cardiovascular disorders. However, the method by which an HS diet impairs cognitive functions such as learning and memory remains open.Methods and resultsIn this study, we found that mice on a 7 week HS diet demonstrated disturbed short‐term memory in an object‐place recognition task, and both 4 week and 7 week HS treatments impaired long‐term memory, as evidenced in a fear conditioning test. Mechanistically, the HS diet inhibited memory‐related long‐term potentiation (LTP) in the hippocampus, while also increasing the levels of reactive oxygen species (ROS) in hippocampal cells and downregulating the expression of synapsin I, synaptophysin, and brain‐derived neurotrophic factor in specific encephalic region.ConclusionThis suggests that oxidative stress or synaptic protein/neurotrophin deregulation was involved in the HS diet‐induced memory impairment. Thus, the present study provides novel insights into the mechanisms of memory impairment caused by excessive dietary salt, and underlined the importance of controlling to salt absorb quantity.
Stressful life events induce abnormalities in emotional and cognitive behaviour. The endogenous opioid system plays an essential role in stress adaptation and coping strategies. In particular, the µ-opioid receptor (μR), one of the major opioid receptors, strongly influences memory processing in that alterations in μR signalling are associated with various neuropsychiatric disorders. However, it remains unclear whether μR signalling contributes to memory impairments induced by acute stress. Here, we utilized pharmacological methods and cell-type-selective/non-cell-type-selective μR depletion approaches combined with behavioural tests, biochemical analyses, and in vitro electrophysiological recordings to investigate the role of hippocampal μR signalling in memory-retrieval impairment induced by acute elevated platform (EP) stress in mice. Biochemical and molecular analyses revealed that hippocampal μRs were significantly activated during acute stress. Blockage of hippocampal μRs, non-selective deletion of μRs or selective deletion of μRs on GABAergic neurons (μR GABA) reversed EP-stress-induced impairment of memory retrieval, with no effect on the elevation of serum corticosterone after stress. Electrophysiological results demonstrated that stress depressed hippocampal GABAergic synaptic transmission to CA1 pyramidal neurons, thereby leading to excitation/inhibition (E/I) imbalance in a μR GABA-dependent manner. Pharmaceutically enhancing hippocampal GABA A receptor-mediated inhibitory currents in stressed mice restored their memory retrieval, whereas inhibiting those currents in the unstressed mice mimicked the stress-induced impairment of memory retrieval. Our findings reveal a novel pathway in which endogenous opioids recruited by acute stress predominantly activate μR GABA to depress GABAergic inhibitory effects on CA1 pyramidal neurons, which subsequently alters the E/I balance in the hippocampus and results in impairment of memory retrieval.
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