Central amygdala is related to the reduction of aggressive behavior by monosodium glutamate ingestion during the period of development in an ADHD model rat.

Introduction: Monosodium glutamate (MSG), an umami substance, stimulates the gut-brain axis communication via gut umami receptors and the subsequent vagus nerves. However, the brain mechanism underlying the effect of MSG ingestion during the developmental period on aggression has not yet been clarified. We first tried to establish new experimental conditions to be more appropriate for detailed analysis of the brain, and then investigated the effects of MSG ingestion on aggressive behavior during the developmental stage of an ADHD rat model.

Potential Therapeutic Effects of MCC1274 on Alzheimer's Disease Pathologies in Mice.

We previously demonstrated that orally supplemented MCC1274 ( MCC1274) mitigated Alzheimer's disease (AD) pathologies in both 7-month-old mice and wild-type mice; thus, 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 mice with memory deficits and amyloid beta saturation in the brain.

Inhibition of Sirt2 Decreases ApoE Secretion in Astrocytes and Microglial Cells.

Amyloid-β (Aβ) accumulation caused by an imbalance of the production and clearance of Aβ in the brain is associated with the development of Alzheimer's disease (ad). Apolipoprotein E (ApoE) (the strongest genetic risk factor) enhances Aβ clearance, preventing Aβ deposition. Sirtuin 2 (Sirt2) is an NAD+-dependent histone deacetylase and its inhibition has been reported to ameliorate memory impairment in ad-like model mice.

Deletion of UCP1 in Tg2576 Mice Increases Body Temperature and Exacerbates Alzheimer's Disease-Related Pathologies.

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.

Tooth Loss Induces Memory Impairment and Glial Activation in Young Wild-Type Mice.

Background: Tooth loss is closely associated with Alzheimer's disease (AD). Previously, we reported that tooth loss induced memory impairment in amyloid precursor protein knock-in mice by decreasing neuronal activity and synaptic protein levels and increasing glial activation, neuroinflammation, and pyramidal neuronal cell loss without altering amyloid-β levels in the hippocampus. However, the effects of tooth loss in young wild-type mice have not been explored yet.

Bifidobacterium breve MCC1274 Supplementation Increased the Plasma Levels of Metabolites with Potential Anti-Oxidative Activity in APP Knock-In Mice.

Background: We previously reported the effects of a probiotic strain, Bifidobacterium breve MCC1274, in improving cognitive function in preclinical and clinical studies. Recently, we demonstrated that supplementation of this strain led to decreased amyloid-β production, attenuated microglial activation, and suppressed inflammation reaction in the brain of APP knock-in (AppNL - G - F) mice.

Objective: In this study, we investigated the plasma metabolites to reveal the mechanism of action of this probiotic strain in this Alzheimer's disease (AD)-like model.

Sustained high body temperature exacerbates cognitive function and Alzheimer's disease-related pathologies.

Global warming is a serious public health threat to people worldwide. High body temperature is one of the important risk factors for Alzheimer's disease (AD), and the body temperature of AD patients has been found to be significantly higher than that of elderly control subjects. However, the effects of high body temperature on cognitive function and AD pathologies have not been completely elucidated.

Probiotic MCC1274 Mitigates Alzheimer's Disease-Related Pathologies in Wild-Type Mice.

Probiotics improve brain function, including memory and cognition, via the microbiome-gut-brain axis. Oral administration of MCC1274 ( MCC1274) improves cognitive function in 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.

Insulin Deficiency Increases Sirt2 Level in Streptozotocin-Treated Alzheimer's Disease-Like Mouse Model: Increased Sirt2 Induces Tau Phosphorylation Through ERK Activation.

Accumulating evidence suggests that insulin deficiency is a risk factor for Alzheimer's disease (AD); however, the underlying molecular mechanisms are not completely understood. Here, we investigated the effects of insulin deficiency on AD-like pathologies using an insulin-deficient amyloid-β (Aβ) precursor protein (APP) transgenic mouse model (Tg2576 mice). Female Tg2576 mice were injected intraperitoneally with streptozotocin (STZ) to induce insulin deficiency, and their body weights, serum glucose levels, and serum insulin levels were evaluated.

Probiotic Bifidobacterium breve Prevents Memory Impairment Through the Reduction of Both Amyloid-β Production and Microglia Activation in APP Knock-In Mouse.

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.

Tooth Loss Induces Memory Impairment and Gliosis in App Knock-In Mouse Models of Alzheimer's Disease.

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.

Establishment of Method for the Determination of Aggregated α-Synuclein in DLB Patient Using RT-QuIC Assay.

Background: The accumulation of aggregated α-synuclein (αSyn) is known as one of the critical reasons to exhibit their variable molecular pathologies and phenotypes in synucleinopathies. Recent studies suggested that the real-time quaking-induced conversion (RT-QuIC) assay is one of the potential methods to detect these αSyn aggregates and could detect the aggregated αSyn in the brain tissue and cerebrospinal fluid (CSF) using the propensity of the prion-like oligomerization.

Objective: We tried to optimize the αSyn RT-QuIC assay based on the aggregation of αSyn in brain samples of synucleinopathies by comparing the conditions of the recently reported αSyn RTQuIC assays.

Dietary Lactoferrin Supplementation Prevents Memory Impairment and Reduces Amyloid-β Generation in J20 Mice.

Lactoferrin (LF) is present in senile plaques and neurofibrillary tangles in the brains of Alzheimer's disease (AD) patients and amyloid-β protein precursor transgenic (AβPP-Tg) mice. LF has anti-inflammatory and antioxidant functions, which exert neuroprotective effects against AD. However, its effects on memory impairment and AD pathogenesis have not been fully examined.

Beta-Amyloid Increases the Expression Levels of Tid1 Responsible for Neuronal Cell Death and Amyloid Beta Production.

Mitochondrial dysfunctions and oxidative stress play important roles in the early pathogenesis of Alzheimer's disease (AD), which also involves the aberrant expression levels of mitochondrial proteins. However, the molecular mechanisms underlying the aberrant expression levels of these proteins in the pathogenesis of AD are still not completely understood. Tid1 (DnaJA3/mtHsp40), a mammalian homolog of the Drosophila tumor suppressor Tid56, is reported to induce mitochondrial fragmentation associated with an increase in reactive oxygen species (ROS) levels, resulting in cell death in some cancer cells.

Alterations of Both Dendrite Morphology and Weaker Electrical Responsiveness in the Cortex of Hip Area Occur Before Rearrangement of the Motor Map in Neonatal White Matter Injury Model.

Hypoxia-ischemia (H-I) in rats at postnatal day 3 causes disorganization of oligodendrocyte development in layers II/III of the sensorimotor cortex without apparent neuronal loss, and shows mild hindlimb dysfunction with imbalanced motor coordination. However, the mechanisms by which mild motor dysfunction is induced without loss of cortical neurons are currently unclear. To reveal the mechanisms underlying mild motor dysfunction in neonatal H-I model, electrical responsiveness and dendrite morphology in the sensorimotor cortex were investigated at 10 weeks of age.

A novel biosensor with high signal-to-noise ratio for real-time measurement of dopamine levels in vivo.

Fast-scan cyclic voltammetry (FSCV) is an established method for measuring dopamine (DA) levels in the brain in real time. However, it is difficult to discriminate DA from other monoamines such as serotonin (5-hydroxytryptamine, 5-HT) and norepinephrine (NE). We report a novel DA-specific biosensor consisting of a carbon-fiber electrode coated with an ion-exchange membrane, a layer containing monoamine oxidase B, and a cellulose membrane.

Disorganization of Oligodendrocyte Development in the Layer II/III of the Sensorimotor Cortex Causes Motor Coordination Dysfunction in a Model of White Matter Injury in Neonatal Rats.

We previously established neonatal white matter injury (WMI) model rat that is made by right common carotid artery dissection at postnatal day 3, followed by 6% hypoxia for 60 min. This model has fewer oligodendrocyte progenitor cells and reduced myelin basic protein (MBP) positive areas in the sensorimotor cortex, but shows no apparent neuronal loss. However, how motor deficits are induced in this model is unclear.

A diagnostic marker for superficial urothelial bladder carcinoma: lack of nuclear ATBF1 (ZFHX3) by immunohistochemistry suggests malignant progression.

Background: Pathological stage and grade have limited ability to predict the outcomes of superficial urothelial bladder carcinoma at initial transurethral resection (TUR). AT-motif binding factor 1 (ATBF1) is a tumor suppressive transcription factor that is normally localized to the nucleus but has been detected in the cytoplasm in several cancers. Here, we examined the diagnostic value of the intracellular localization of ATBF1 as a marker for the identification of high risk urothelial bladder carcinoma.

Dysfunction in Motor Coordination in Neonatal White Matter Injury Model Without Apparent Neuron Loss.

We made a white matter injury (WMI) model with mild hindlimb dysfunction by right common carotid artery occlusion followed by 6% oxygen for 60 min at postnatal day 3 (P3), in which actively proliferating oligodendrocyte (OL) progenitors are mainly damaged. To know whether this model is appropriate for cell therapy using OL progenitors, the pathological response to mild hypoxia-ischemia (H-I) in neurons and OL lineage cells and myelination failure were investigated along with gene expression analysis. In WMI model rats, coordinated motor function, as assessed by the accelerating rotarod test, was impaired.

Arachidonic or Docosahexaenoic Acid Diet Prevents Memory Impairment in Tg2576 Mice.

It is believed that the amyloid β-protein (Aβ) plays a causative role in the development of Alzheimer's disease (AD). The amyloid-β protein precursor (AβPP), a substrate of Aβ, and β-secretase and γ-secretase complex proteins, which process AβPP to generate Aβ, are all membrane proteins. Thus, it is reasonable to assume that alterations in brain lipid metabolism modulate AβPP and/or Aβ metabolism.

Arachidonic acid diet attenuates brain Aβ deposition in Tg2576 mice.

The amyloid β-protein (Aβ) is believed to play a causative role in the development of Alzheimer's disease (AD). Because the amyloid precursor protein (APP), a substrate of Aβ, and β-secretase and γ-secretase complex proteins, which process APP to generate Aβ, are all membrane proteins, it is possible to assume that alterations in brain lipid metabolism modulate APP and/or Aβ metabolism. However, the role of polyunsaturated fatty acids in Aβ metabolism remains unknown.

Phosphatidylinositol-glycan-phospholipase D is involved in neurodegeneration in prion disease.

PrPSc is formed from a normal glycosylphosphatidylinositol (GPI)-anchored prion protein (PrPC) by a posttranslational modification. Most GPI-anchored proteins have been shown to be cleaved by GPI phospholipases. Recently, GPI-phospholipase D (GPI-PLD) was shown to be a strictly specific enzyme for GPI anchors.

Early constraint-induced movement therapy promotes functional recovery and neuronal plasticity in a subcortical hemorrhage model rat.

Constraint-induced movement therapy (CIMT) promotes functional recovery of impaired forelimbs after hemiplegic strokes, including intracerebral hemorrhage (ICH). We used a rat model of subcortical hemorrhage to compare the effects of delivering early or late CIMT after ICH. The rat model was made by injecting collagenase into the globus pallidus near the internal capsule, and then forcing rats to use the affected forelimb for 7 days starting either 1 day (early CIMT) or 17 days (late CIMT) after the lesion.

Tooth loss might not alter molecular pathogenesis in an aged transgenic Alzheimer's disease model mouse.

Background And Objective: Previous studies have reported that tooth loss is a risk factor of Alzheimer's disease (AD). However, the association between tooth loss and cognition and the impact of tooth loss on the molecular pathogenesis of AD remain elusive. In this study, we tested the effect of tooth loss on learning and memory and on the molecular pathogenesis of AD in an aged AD model mice.