Corticothalamic input derived from corticospinal neurons contributes to chronic neuropathic pain after spinal cord injury.

Neuropathic pain is a significant and persistent issue for individuals with spinal cord injuries (SCI), severely impacting their quality of life. While changes at the peripheral and spinal levels are known to contribute to SCI-related pain, whether and how supraspinal centers contribute to post SCI chronic neuropathic pain is poorly understood. Here, we first validated delayed development of chronic neuropathic pain in mice with moderate contusion SCI.

Characterizing Early-Onset Alzheimer Disease Using Multiprobe PET/MRI: An AT(N) Framework-Based Study.

Purpose: Early-onset Alzheimer disease (EOAD) is rare, highly heterogeneous, and associated with poor prognosis. This AT(N) Framework-based study aimed to compare multiprobe PET/MRI findings between EOAD and late-onset Alzheimer disease (LOAD) patients and explore potential imaging biomarkers for characterizing EOAD.

Methods: Patients with AD who underwent PET/MRI in our PET center were retrospectively reviewed and grouped according to the age at disease onset: EOAD, younger than 60 years; and LOAD, 60 years or older.

Clinical and genetic characteristics in a central-southern Chinese cohort of early-onset Alzheimer's disease.

Background: Mutations in the presenilin-1 (), presenilin-2 (), and amyloid precursor protein () genes have been commonly identified in early-onset Alzheimer's disease (EOAD). Some of the mutations in the three causative genes, especially the gene, result in variable phenotypes and exhibit clinical heterogeneity among EOAD families.

Methods: Using next-generation sequencing (NGS), we performed genetic screening in a Chinese cohort of 18 patients with EOAD, consisting of five familial EOAD and 13 sporadic cases.

Global cognitive effects of second-generation antidepressants in patients with Alzheimer's disease: A systematic review and meta-analysis of randomized controlled trials.

The second-generation antidepressants (SGAs) are used widely in patients with Alzheimer's disease (AD) for the treatment of mood disorder, sleep disturbance and psychiatric symptoms. Several evidences from AD mice confirmed that antidepressants could delaying cognitive decline. However, the conclusions varied in randomized controlled trials (RCTs) based on patients.

F-APN-1607 Tau Positron Emission Tomography Imaging for Evaluating Disease Progression in Alzheimer's Disease.

Purpose: F-APN-1607 is a novel tau positron emission tomography (PET) tracer characterized with high binding affinity for 3- and 4-repeat tau deposits. The aim was to analyze the spatial distribution of F-APN-1607 PET imaging in Alzheimer's disease (AD) subjects with different stages and to investigate the relationship between the change of tau deposition and overall disease progression.

Methods: We retrospectively analyzed the F-APN-1607 PET imaging of 31 subjects with clinically and imaging defined as AD.

Sixteen-Week Interventional Study to Evaluate the Clinical Effects and Safety of Rivastigmine Capsules in Chinese Patients with Alzheimer's Disease.

Background: Rivastigmine is a cholinesterase inhibitor, approved for the treatment of mild-to-moderate dementia of Alzheimer's type.

Objective: To explore the efficacy and safety of the maximal tolerated dose of rivastigmine capsules in Chinese patients with mild-to-moderate Alzheimer's disease (AD).

Methods: The study was a multicenter, open-label, single-arm, phase IV clinical study in mild-to-moderate drug-naïve AD patients treated with rivastigmine capsules.

MicroRNA-26a/Death-Associated Protein Kinase 1 Signaling Induces Synucleinopathy and Dopaminergic Neuron Degeneration in Parkinson's Disease.

Background: Death-associated protein kinase 1 (DAPK1) is a widely distributed serine/threonine kinase that is critical for cell death in multiple neurological disorders, including Alzheimer's disease and stroke. However, little is known about the role of DAPK1 in the pathogenesis of Parkinson's disease (PD), the second most common neurodegenerative disorder.

Methods: We used Western blot and immunohistochemistry to evaluate the alteration of DAPK1.

Intranasal Insulin Prevents Anesthesia-induced Cognitive Impairments in Aged Mice.

Background: Preclinical and clinical evidence suggests that elderly individuals are at increased risk of cognitive decline after general anesthesia. General anesthesia is also believed to be a risk factor for Postoperative Cognitive Dysfunction (POCD) and Alzheimer's Disease (AD). Intranasal administration of insulin, which delivers the drug directly into the brain, improves memory and cognition in both animal studies and small clinical trials.

Correction: A Chinese version of the Language Screening Test (CLAST) for early-stage stroke patients.

[This corrects the article DOI: 10.1371/journal.pone.

A Chinese version of the Language Screening Test (CLAST) for early-stage stroke patients.

There is a severe lack of aphasia screening tools for bedside use in Chinese. A number of aphasia assessment tools have recently been developed abroad, but some of these scales were not suitable for patients with acute stroke. The Language Screening Test (which includes two parallel versions [a/b]) in French has been proven to be an effective and time-saving aphasia screening scale for early-stage stroke patients.

Intranasal insulin restores insulin signaling, increases synaptic proteins, and reduces Aβ level and microglia activation in the brains of 3xTg-AD mice.

Decreased brain insulin signaling has been found recently in Alzheimer's disease (AD). Intranasal administration of insulin, which delivers the drug directly into the brain, improves memory and cognition in both animal studies and small clinical trials. However, the underlying mechanisms are unknown.

Intranasal insulin prevents anesthesia-induced hyperphosphorylation of tau in 3xTg-AD mice.

Background: It is well documented that elderly individuals are at increased risk of cognitive decline after anesthesia. General anesthesia is believed to be a risk factor for Alzheimer's disease (AD). Recent studies suggest that anesthesia may increase the risk for cognitive decline and AD through promoting abnormal hyperphosphorylation of tau, which is crucial to neurodegeneration seen in AD.

Intracerebroventricular streptozotocin exacerbates Alzheimer-like changes of 3xTg-AD mice.

Alzheimer's disease (AD) involves several possible molecular mechanisms, including impaired brain insulin signaling and glucose metabolism. To investigate the role of metabolic insults in AD, we injected streptozotocin (STZ), a diabetogenic compound if used in the periphery, into the lateral ventricle of the 6-month-old 3xTg-AD mice and studied the cognitive function as well as AD-like brain abnormalities, such as tau phosphorylation and Aβ accumulation, 3-6 weeks later. We found that STZ exacerbated impairment of short-term and spatial reference memory in 3xTg-AD mice.

Temperature control can abolish anesthesia-induced tau hyperphosphorylation and partly reverse anesthesia-induced cognitive impairment in old mice.

Aims: Anesthesia is related to cognitive impairment and the risk for Alzheimer's disease. Hypothermia during anesthesia can lead to abnormal hyperphosphorylation of tau, which has been speculated to be involved in anesthesia-induced cognitive impairment. The aim of this study was to investigate whether maintenance of the tau phosphorylation level by body temperature control during anesthesia could reverse the cognitive dysfunction in C57BL/6 mice.

Rapamycin decreases tau phosphorylation at Ser214 through regulation of cAMP-dependent kinase.

Preventing or reducing tau hyperphosphorylation is considered to be a therapeutic strategy in the treatment of Alzheimer's disease (AD). Rapamycin may be a potential therapeutic agent for AD, because the rapamycin-induced autophagy may enhance the clearance of the hyperphosphorylated tau. However, recent rodent studies show that the protective effect of rapamycin may not be limited in the autophagic clearance of the hyperphosphorylated tau.

Pretreatment of PC12 cells with 17β-estradiol prevents Aβ-induced down-regulation of CREB phosphorylation and prolongs inhibition of GSK-3β.

It is believed that estrogen protects neurons against various toxicities like that from amyloid β (Aβ) in Alzheimer's disease (AD). In the present study, we investigated the effects of Aβ1-42 on the activities of cyclic-AMP response element-binding protein (CREB) and glycogen synthase kinase-3β (GSK-3β), two key proteins associated with learning and memory, and the effects of 17β-estradiol on Aβ(1-42)-induced changes of CREB and GSK-3β in PC12 cells. We found that Aβ1-42 induced a decrease in phosphorylation of CREB at Ser133 (CREB pS133) and caused a transient (30 min) up-regulation of the inhibitory GSK-3β phosphorylation at Ser9 (GSK-3β pS9), followed by down-regulation of GSK-3β pS9.

Brain gene expression of a sporadic (icv-STZ Mouse) and a familial mouse model (3xTg-AD mouse) of Alzheimer's disease.

Alzheimer's disease (AD) can be divided into sporadic AD (SAD) and familial AD (FAD). Most AD cases are sporadic and may result from multiple etiologic factors, including environmental, genetic and metabolic factors, whereas FAD is caused by mutations of presenilins or amyloid-β (Aβ) precursor protein (APP). A commonly used mouse model for AD is 3xTg-AD mouse, which is generated by over-expression of mutated presenilin 1, APP and tau in the brain and thus represents a mouse model of FAD.

A non-transgenic mouse model (icv-STZ mouse) of Alzheimer's disease: similarities to and differences from the transgenic model (3xTg-AD mouse).

Alzheimer's disease (AD) can be divided into sporadic AD (SAD) and familial AD (FAD). Most AD cases are sporadic and result from multiple etiologic factors, including environmental, genetic, and metabolic factors, whereas FAD is caused by mutations in the presenilins or amyloid-β (Aβ) precursor protein (APP) genes. A commonly used animal model for AD is the 3xTg-AD transgenic mouse model, which harbors mutated presenilin 1, APP, and tau genes and thus represents a model of FAD.

Developmental regulation of protein O-GlcNAcylation, O-GlcNAc transferase, and O-GlcNAcase in mammalian brain.

O-GlcNAcylation is a common posttranslational modification of nucleocytoplasmic proteins by β-N-acetylglucosamine (GlcNAc). The dynamic addition and removal of O-GlcNAc groups to and from proteins are catalyzed by O-linked N-acetylglucosamine transferase (O-GlcNAc transferase, OGT) and β-N-acetylglucosaminidase (O-GlcNAcase, OGA), respectively. O-GlcNAcylation often modulates protein phosphorylation and regulates several cellular signaling and functions, especially in the brain.

Tau phosphorylation and μ-calpain activation mediate the dexamethasone-induced inhibition on the insulin-stimulated Akt phosphorylation.

Evidence has suggested that insulin resistance (IR) or high levels of glucocorticoids (GCs) may be linked with the pathogenesis and/or progression of Alzheimer's disease (AD). Although studies have shown that a high level of GCs results in IR, little is known about the molecular details that link GCs and IR in the context of AD. Abnormal phosphorylation of tau and activation of μ-calpain are two key events in the pathology of AD.

Differential effects of an O-GlcNAcase inhibitor on tau phosphorylation.

Abnormal hyperphosphorylation of microtubule-associated protein tau plays a crucial role in neurodegeneration in Alzheimer's disease (AD). The aggregation of hyperphosphorylated tau into neurofibrillary tangles is also a hallmark brain lesion of AD. Tau phosphorylation is regulated by tau kinases, tau phosphatases, and O-GlcNAcylation, a posttranslational modification of proteins on the serine or threonine residues with β-N-acetylglucosamine (GlcNAc).

Human tau may modify glucocorticoids-mediated regulation of cAMP-dependent kinase and phosphorylated cAMP response element binding protein.

Phosphorylation of the cAMP response element binding protein (CREB) by cAMP-dependent kinase (PKA) is critical to memory formation. However, activation of PKA can also increase tau phosphorylation, which may contribute to memory impairment. Therefore, the regulation of PKA may be part of the mechanism by which glucocorticoids (GCs) influence memory.

1,5-dicaffeoylquinic acid protects primary neurons from amyloid β 1-42-induced apoptosis via PI3K/Akt signaling pathway.

Background: Recently, 1,5-dicaffeoylquinic acid (1,5-DQA), a caffeoylquinic acid derivative isolated from Aster scaber, was found to have neuroprotective effects. However, the protective mechanisms of 1,5-DQA have not yet been clearly identified. The purpose of this study was to explore the protective mechanisms of 1,5-DQA on neuronal culture.