Antarctic Krill Oil Exhibited Synergistic Effects with Nobiletin and Theanine on Regulating Ligand-Specific Receptor-Mediated Transcytosis in Blood-Brain Barrier by Inhibiting Alkaline Phosphatase in SAMP8 Mice.

Blood-brain barrier (BBB) impairment is related to the development of Alzheimer's disease (AD), which is dependent not only on tight junction but also on transcytosis of brain endothelial cells (BECs) in the BBB. Aging induces the decrease of ligand-specific receptor-mediated transcytosis (RMT) and the increase of non-specific caveolar transcytosis in BECs, which lead to the entry into parenchyma of neurotoxic proteins and the smaller therapeutic index in central nervous system drug delivery, further provoking neurodegenerative disease. A previous study suggests that sea-derived Antarctic krill oil (AKO) exhibits synergistic effects with land-derived nobiletin (NOB) and theanine (THE) on ameliorating memory and cognitive deficiency in SAMP8 mice. However, it is still unclear whether BBB change is involved. Hence, the effects of AKO combined with NOB and THE on aging-induced BBB impairment, including tight junction between BECs, ligand-specific RMT, and non-specific caveolar transcytosis in BECs, are investigated. The results suggest that AKO exhibits synergistic effects with NOB and THE on regulating ligand-specific RMT in BBB by inhibiting alkaline phosphatase (ALPL). The study provides a potential strategy candidate or targeted dietary patterns to prevent and treat AD by improving the BBB function.

Antarctic krill oil exhibited synergistic effects with nobiletin and theanine in ameliorating memory and cognitive deficiency in SAMP8 mice: Applying the perspective of the sea-land combination to retard brain aging.

The complex pathogenesis of Alzheimer's disease (AD) leads to a limited therapeutic effect; therefore, the combination of multiple bioactive ingredients may be more effective in improving AD due to synergistic effects. Based on the perspective of the sea-land combination, the effects of sea-derived Antarctic krill oil (AKO) combined with land-derived nobiletin (Nob) and L-theanine (The) on memory loss and cognitive deficiency were studied in senescence-accelerated prone 8 mice (SAMP8). The results demonstrated that AKO combined with The significantly increased the number of platform crossings in the Morris water maze test by 1.6-fold, and AKO combined with Nob significantly increased the preference index in a novel object recognition test. AKO exhibited synergistic effects with Nob and The in ameliorating recognition memory and spatial memory deficiency in SAMP8 mice, respectively. Further research of the mechanism indicated that AKO exhibited synergistic effects with Nob in suppressing ß-amyloid (Aß) aggregation, neurofibrillary tangles, and apoptosis and neuroinflammation, while the synergistic effects of AKO and The involved in synaptic plasticity and anti-neuroinflammation, which revealed that the combination was complex, not a mechanical addition. These findings revealed that the sea-land combination may be an effective strategy to treat and alleviate AD.

Abnormal resting-state functional connectivity of hippocampal subfields in patients with major depressive disorder.

BACKGROUND: Many studies have found that the hippocampus plays a very important role in major depressive disorder (MDD). The hippocampus can be divided into three subfields: the cornu ammonis (CA), dentate gyrus (DG) and subiculum. Each subfield of the hippocampus has a unique function and are differentially associated with the pathological mechanisms of MDD. However, no research exists to describe the resting state functional connectivity of each hippocampal subfield in MDD. METHODS: Fifty-five patients with MDD and 25 healthy controls (HCs) matched for gender, age and years of education were obtained. A seed-based method that imposed a template on the whole brain was used to assess the resting-state functional connectivity (rsFC) of each hippocampal subfield. RESULTS: Patients with MDD demonstrated increased connectivity in the left premotor cortex (PMC) and reduced connectivity in the right insula with the CA seed region. Increased connectivity was reported in the left orbitofrontal cortex (OFC) and left ventrolateral prefrontal cortex (vlPFC) with the DG seed region. The subiculum seed region revealed increased connectivity with the left premotor cortex (PMC), the right middle frontal gyrus (MFG), the left ventrolateral prefrontal cortex (vlPFC) and reduced connectivity with the right insula. ROC curves confirmed that the differences between groups were statistically significant. CONCLUSION: The results suggest that the CA, DG and subiculum have significant involvement with MDD. Specifically, the abnormal functional connectivity of the CA may be related to bias of coding and integration of information in patients with MDD. The abnormal functional connectivity of the DG may be related to the impairment of working memory in patients with MDD, and the abnormal functional connectivity of the subiculum may be related to cognitive impairment and negative emotions in patients with MDD.