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We previously demonstrated that orally supplemented Bifidobacterium breve MCC1274 (B. breve MCC1274) mitigated Alzheimer's disease (AD) pathologies in both 7-month-old AppNL-G-F mice and wild-type mice; thus, B. breve MCC1274 supplementation might potentially prevent the progression of AD. However, the possibility of using this probiotic as a treatment for AD remains unclear. Thus, we investigated the potential therapeutic effects of this probiotic on AD using 17-month-old AppNL-G-F mice with memory deficits and amyloid beta saturation in the brain. B. breve MCC1274 supplementation ameliorated memory impairment via an amyloid-cascade-independent pathway. It reduced hippocampal and cortical levels of phosphorylated extracellular signal-regulated kinase and c-Jun N-terminal kinase as well as heat shock protein 90, which might have suppressed tau hyperphosphorylation and chronic stress. Moreover, B. breve MCC1274 supplementation increased hippocampal synaptic protein levels and upregulated neuronal activity. Thus, B. breve MCC1274 supplementation may alleviate cognitive dysfunction by reducing chronic stress and tau hyperphosphorylation, thereby enhancing both synaptic density and neuronal activity in 17-month-old AppNL-G-F mice. Overall, this study suggests that B. breve MCC1274 has anti-AD effects and can be used as a potential treatment for AD. [ABSTRACT FROM AUTHOR]

We previously demonstrated that the Alzheimer's disease (AD)-like model mice, Tg2576, housed at a high ambient temperature of 30 °C for 13 months, exhibited increased body temperature, which increased amyloid-β (Aβ) levels and tau stability, leading to tau phosphorylation and ultimately inducing memory impairment. Here, we aimed to exclude the possible effect of environmental factors associated with the difference in ambient temperature (23 °C vs. 30 °C) and to further clarify the effects of elevated body temperature on AD-like pathologies. We generated uncoupling protein 1 (UCP1) deletion in Tg2576 mice, Tg2576/UCP1−/−, because UCP1 deletion mice show a sustained rise in body temperature at normal room temperature. As expected, the body temperature in Tg2576/UCP1−/− mice was higher than that in Tg2576/ UCP1+/+ mice at 23 °C, which was accompanied by upregulated Aβ levels due to increased β-secretase (BACE1) and decreased neprilysin (NEP) protein levels in the brains of Tg2576/UCP1−/− mice compared with those in the Tg2576/ UCP1+/+ mice. Elevated body temperature also increased total tau levels, leading to enhanced phosphorylation, heat shock protein induction, and activated tau kinases. Furthermore, elevated body temperature enhanced glial activation and decreased synaptic protein levels in the brain. Taken together, these findings demonstrate that elevated body temperatures exacerbate AD-like pathologies. [ABSTRACT FROM AUTHOR]

Probiotics improve brain function, including memory and cognition, via the microbiome–gut–brain axis. Oral administration of Bifidobacterium breve MCC1274 (B. breve MCC1274) improves cognitive function in AppNL-G-F mice and mild cognitive impairment (MCI) subjects, and mitigates Alzheimer's disease (AD)-like pathologies. However, its effects on wild-type (WT) mice have not yet been explored. Thus, the effects of B. breve MCC1274 on AD-like pathologies in two-month-old WT mice were investigated, which were orally administered B. breve MCC1274 for four months. Aβ levels, amyloid precursor protein (APP), APP processing enzymes, phosphorylated tau, synaptic protein levels, glial activity, and cell proliferation in the subgranular zone of the dentate gyrus were evaluated. Data analysis was performed using Student's t-test, and normality was tested using the Shapiro–Wilk test. Oral administration of B. breve MCC1274 in WT mice decreased soluble hippocampal Aβ42 levels by reducing presenilin1 protein levels, and reduced phosphorylated tau levels. It also activated the protein kinase B (Akt)/glycogen synthase kinase-3β (GSK-3β) pathway, which may be responsible for the reduction in presenilin1 levels and inhibition of tau phosphorylation. B. breve MCC1274 supplementation attenuated microglial activation and elevated synaptic protein levels in the hippocampus. These findings suggest that B. breve MCC1274 may mitigate AD-like pathologies in WT mice by decreasing Aβ42 levels, inhibiting tau phosphorylation, attenuating neuroinflammation, and improving synaptic protein levels. [ABSTRACT FROM AUTHOR]

Background: Probiotic supplementation reestablishes microbiome diversity and improves brain function in Alzheimer's disease (AD); their molecular mechanisms, however, have not yet been fully illustrated.Objective: We investigated the effects of orally supplemented Bifidobacterium breve MCC1274 on cognitive function and AD-like pathologies in AppNL-G-F mice.Methods: Three-month-old AppNL-G-F mice were orally supplemented with B. breve MCC1274 for four months. The short-term memory function was evaluated using a novel object recognition test. Amyloid plaques, amyloid-β (Aβ) levels, Aβ fibril, amyloid-β protein precursor and its processing enzymes, its metabolic products, glial activity, and cell proliferation in the subgranular zone of the dentate gyrus were evaluated by immunohistochemistry, Aβ ELISA, western blotting, and immunofluorescence staining. The mRNA expression levels of pro- and anti-inflammatory cytokines were determined by qRT-PCR analysis.Results: We found that the oral B. breve MCC1 274 supplementation prevented memory impairment in AppNL-G-F mice and decreased hippocampal Aβ levels through the enhancement of the a-disintegrin and metalloproteinase 10 (ADAM10) level. Moreover, administration of the probiotic activated the ERK/HIF-1α signaling pathway responsible for increasing the ADAM10 level and also attenuated microglial activation, which in turn led to reduction in the mRNA expression levels of pro-inflammatory cytokines in the brain. In addition, B. breve MCC1274 supplementation increased the level of synaptic proteins in the hippocampus.Conclusion: Our findings support the possibility that oral B. breve MCC1274 supplementation might be used as a potential preventive therapy for AD progression. [ABSTRACT FROM AUTHOR]

Background: Epidemiological studies have shown that tooth loss is associated with Alzheimer's disease (AD) and dementia. However, the molecular and cellular mechanisms by which tooth loss causes AD remain unclear.Objective: We investigated the effects of tooth loss on memory impairment and AD pathogenesis in AppNL-G-F mice.Methods: Maxillary molar teeth on both sides were extracted from 2-month-old AppNL-G-F mice, and the mice were reared for 2 months. The short- and long-term memory functions were evaluated using a novel object recognition test and a passive avoidance test. Amyloid plaques, amyloid-β (Aβ) levels, glial activity, and neuronal activity were evaluated by immunohistochemistry, Aβ ELISA, immunofluorescence staining, and western blotting. The mRNA expression levels of neuroinflammatory cytokines were determined by qRT-PCR analysis.Results: Tooth loss induced memory impairment via an amyloid-cascade-independent pathway, and decreased the neuronal activity, presynaptic and postsynaptic protein levels in both the cortex and hippocampus. Interestingly, we found that tooth loss induced glial activation, which in turn leads to the upregulation of the mRNA expression levels of the neuroinflammation cytokines tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and IL-1β in the hippocampus. We also found that tooth loss activated a stress-activated protein kinase, c-Jun N-terminal kinase (JNK), and increased heat shock protein 90 (HSP90) levels in the hippocampus, which may lead to a glial activation.Conclusion: Our findings suggest that taking care of teeth is very important to preserve a healthy oral environment, which may reduce the risk of cognitive dysfunction. [ABSTRACT FROM AUTHOR]