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.

Altered brain function in patients with acrophobia: A voxel-wise degree centrality analysis.

AIM: To explore the local spontaneous neural activity and whole-brain functional connectivity patterns in the resting brain of acrophobia patients. METHODS: 50 patients with acrophobia and 47 healthy controls were selected for this study. All participants underwent resting-state MRI scans after enrollment. The imaging data were then analyzed using a voxel-based degree centrality (DC) method, and seed-based functional connectivity (FC) correlation analysis was used to explore the correlation between abnormal functional connectivity and clinical symptom scales in acrophobia. The severity of symptoms was evaluated using self-report and behavioral measures. RESULTS: Compared to controls, acrophobia patients showed higher DC in the right cuneus and left middle occipital gyrus and significantly lower DC in the right cerebellum and left orbitofrontal cortex (p < 0.01, GRF corrected). Additionally, there were negative correlations between the acrophobia questionnaire avoidance (AQ- Avoidance) scores and right cerebellum-left perirhinal cortex FC (r = -0.317, p = 0.025) and between scores of the 7-item generalized anxiety disorder scale and left middle occipital gyrus-right cuneus FC (r = -0.379, p = 0.007). In the acrophobia group, there was a positive correlation between behavioral avoidance scale and right cerebellum-right cuneus FC (r = 0.377, p = 0.007). CONCLUSIONS: The findings indicated that there are local abnormalities in spontaneous neural activity and functional connectivity in the visual cortex, cerebellum, and orbitofrontal cortex in patients with acrophobia.

Altered spontaneous neural activity in frontal and visual regions in patients with acrophobia.

BACKGROUND: Acrophobia is a prevalent type of specific phobia, which frequently leads to functional impairments and occupational limitations. However, the neural pathology of acrophobia is still largely unknown. METHODS: 26 acrophobic patients and 30 healthy controls were enrolled in this study. All participants underwent a resting-state fMRI scan. Severity of symptoms was evaluated using self-report and behavioral measures. The regional homogeneity (ReHo) and seed-based functional connectivity (FC) were then examined. RESULTS: Compared to controls, acrophobic patients demonstrated higher ReHo in the right fusiform gyrus and lower ReHo in the bilateral superior frontal gyrus. Lower FC of right fusiform gyrus-bilateral caudate, right fusiform gyrus-right parahippocampal gyrus, and left medial superior frontal gyrus-left cuneus was also found in the acrophobia group. Additionally, there were negative correlations between behavior avoidance scores and FC of right fusiform gyrus- right parahippocampal gyrus (r = -0.42, p = 0.04) and between scores of the 7-item generalized anxiety disorder scale and FC of left medial superior frontal gyrus- left cuneus (r = -0.40, p = 0.049) in the acrophobia group. LIMITATIONS: Owing to the cross-sectional design, it was unclear whether the functional abnormalities found in the acrophobic patients were related to state or trait effects. CONCLUSIONS: Preliminary results indicated that acrophobic patients revealed abnormal brain function in orbitofrontal cortex, medial prefrontal cortex, and visual regions. These abnormalities may be helpful in understanding the possible neurobiological mechanism of acrophobia and may serve as potential intervention and prevention targets.

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.