CSF total tau as a proxy of synaptic degeneration.

Cerebrospinal fluid (CSF) total tau (t-tau) is considered a biomarker of neuronal degeneration alongside brain atrophy and fluid neurofilament light chain protein (NfL) in biomarker models of Alzheimer's disease (AD). However, previous studies show that CSF t-tau correlates strongly with synaptic dysfunction/degeneration biomarkers like neurogranin (Ng) and synaptosomal-associated protein 25 (SNAP25). Here, we compare the association between CSF t-tau and synaptic degeneration and axonal/neuronal degeneration biomarkers in cognitively unimpaired and impaired groups from two independent cohorts.

Glial reactivity correlates with synaptic dysfunction across aging and Alzheimer's disease.

Previous studies suggest glial and neuronal changes may trigger synaptic dysfunction in Alzheimer's disease (AD), but the link between their markers and synaptic abnormalities in the living brain remains unclear. We investigated the association between glial reactivity and synaptic dysfunction biomarkers in cerebrospinal fluid (CSF) from 478 individuals in cognitively unimpaired (CU) and cognitively impaired (CI) individuals. We measured amyloid-β (Aβ), phosphorylated tau (pTau181), astrocyte reactivity (GFAP), microglial activation (sTREM2), and synaptic markers (GAP43, neurogranin).

Utility of plasma GFAP as a secondary endpoint for clinical trials in Alzheimer's disease.

Background: Clinical trials have recently incorporated plasma glial fibrillary acidic protein (GFAP) as an exploratory endpoint. To include plasma GFAP as a secondary endpoint, it is essential to characterize its longitudinal progression in target populations.

Objective: To evaluate the potential use of plasma GFAP changes as a secondary endpoint in Alzheimer's disease trials.

Microglial Responses to MSC-EVs Treatment in Animal and Cellular Models of Ischemic Stroke: a Systematic Review with Meta-analysis.

The modulation of microglial reactivity has emerged as a potential target for developing ischemic stroke therapies. Mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) possess immunomodulatory properties that may influence microglial responses following ischemia. However, individual studies assessing this influence have provided limited results.

Diagnostic performance of Alzheimer's disease blood biomarkers in a Brazilian cohort.

Blood-based biomarkers (BBMs) have emerged as promising tools to enhance Alzheimer's disease (AD) diagnosis. Despite two-thirds of dementia cases occurring in the Global South, research on BBMs has predominantly focused on populations from the Global North. This geographical disparity hinders our understanding of BBM performance in diverse populations.

Impact of the polygenic risk scores for attention-deficit/hyperactivity disorder in Alzheimer's disease.

Introduction: Epidemiological studies indicate a link between attention-deficit/hyperactivity disorder (ADHD) and elevated risk of dementia. However, the impact of ADHD on cognition and Alzheimer's disease (AD) biomarkers in individuals with cognitive impairment remains unclear.

Methods: We computed weighted ADHD polygenic risk scores (ADHD-PRS) in 938 cognitively impaired participants (674 mild cognitive impairment [MCI] and 264 dementia; mean age 73.

Spontaneously Hypertensive Rats Present Exacerbated Focal Stroke Behavioral Outcomes.

This study aimed to analyze the effects of systemic arterial hypertension (SAH) in a model of permanent ischemic stroke (focal ischemia due to thermocoagulation of pial vessels) on sensorimotor function (cylinder test and patch removal test), behavioral tasks (novelty habituation memory open field task) and cerebral infarct size in adult male spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto rats (WKY) for 42 days after the occurrence of a stroke. We observed that the stroke caused asymmetry in the front paws and delayed adhesive removal. These effects were spontaneously reduced in WKY rats, but not in SHR.

Glial reactivity is linked to synaptic dysfunction across the aging and Alzheimer's disease spectrum.

Previous studies have shown that glial and neuronal changes may trigger synaptic dysfunction in Alzheimer's disease(AD). However, the link between glial and neuronal markers and synaptic abnormalities in the living brain is poorly understood. Here, we investigated the association between biomarkers of astrocyte and microglial reactivity and synaptic dysfunction in 478 individuals across the aging and AD spectrum from two cohorts with available CSF measures of amyloid-β(Aβ), phosphorylated tau(pTau181), astrocyte reactivity(GFAP), microglial activation(sTREM2), and synaptic biomarkers(GAP43 and neurogranin).

Neuropsychiatric Symptoms and Microglial Activation in Patients with Alzheimer Disease.

Importance: Neuropsychiatric symptoms are commonly encountered and are highly debilitating in patients with Alzheimer disease. Understanding their underpinnings has implications for identifying biomarkers and treatment for these symptoms.

Objective: To evaluate whether glial markers are associated with neuropsychiatric symptoms in individuals across the Alzheimer disease continuum.

Caveolin-1 influences mitochondrial plasticity and function in hepatic stellate cell activation.

Caveolin-1 (Cav-1) is an integral membrane protein present in all organelles, responsible for regulating and integrating multiple signals as a platform. Mitochondria are extremely adaptable to external cues in chronic liver diseases, and expression of Cav-1 may affect mitochondrial flexibility in hepatic stellate cells (HSCs) activation. We previously demonstrated that exogenous expression of Cav-1 was sufficient to increase some classical markers of activation in HSCs.

Functional Recovery Caused by Human Adipose Tissue Mesenchymal Stem Cell-Derived Extracellular Vesicles Administered 24 h after Stroke in Rats.

Ischemic stroke is a major cause of death and disability, intensely demanding innovative and accessible therapeutic strategies. Approaches presenting a prolonged period for therapeutic intervention and new treatment administration routes are promising tools for stroke treatment. Here, we evaluated the potential neuroprotective properties of nasally administered human adipose tissue mesenchymal stem cell (hAT-MSC)-derived extracellular vesicles (EVs) obtained from healthy individuals who underwent liposuction.

Ethylmalonic acid impairs bioenergetics by disturbing succinate and glutamate oxidation and induces mitochondrial permeability transition pore opening in rat cerebellum.

Tissue accumulation and high urinary excretion of ethylmalonic acid (EMA) are found in ethylmalonic encephalopathy (EE), an inherited disorder associated with cerebral and cerebellar atrophy whose pathogenesis is poorly established. The in vitro and in vivo effects of EMA on bioenergetics and redox homeostasis were investigated in rat cerebellum. For the in vitro studies, cerebellum preparations were exposed to EMA, whereas intracerebellar injection of EMA was used for the in vivo evaluation.

Guanosine Neuroprotection of Presynaptic Mitochondrial Calcium Homeostasis in a Mouse Study with Amyloid-β Oligomers.

Amyloid-β oligomers (AβOs) toxicity causes mitochondrial dysfunction, leading to synaptic failure in Alzheimer's disease (AD). Considering presynaptic high energy demand and tight Ca regulation, impairment of mitochondrial function can lead to deteriorated neural activity and cell death. In this study, an AD mouse model induced by ICV (intracerebroventricular) injection of AβOs was used to investigate the toxicity of AβOs on presynaptic function.

The neuroprotective role of melatonin in a gestational hypermethioninemia model.

Elevated levels of methionine in blood characterize the hypermethioninemia, which may have genetic or non-genetic origin, as for example from high protein diet. Born rats from hypermethioninemic mothers presented cerebral oxidative stress, inhibition of Na,K-ATPase, memory deficit and ultrastructure cerebral changes. Melatonin is a hormone involved in circadian rhythm and has antioxidant effects.

Exogenous expression of caveolin-1 is sufficient for hepatic stellate cell activation.

Caveolin-1 (Cav-1) expression is increased in hepatic stellate cells (HSC) upon liver cirrhosis and it functions as an integral membrane protein of lipid rafts and caveolae that regulates and integrates multiple signals as a platform. This study aimed to evaluate the role of Cav-1 in HSC. Thus, the effects of exogenous expression of Cav-1 in GRX cells, a model of activated HSC, were determined.

Dipyridamole impairs autophagic flux and exerts antiproliferative activity on prostate cancer cells.

Autophagy is a cellular bulk degradation process used as an alternative source of energy and metabolites and implicated in various diseases. Inefficient autophagy in nutrient-deprived cancer cells would be beneficial for cancer therapy making its modulation valuable as a therapeutic strategy for cancer treatment, especially in combination with chemotherapy. Dipyridamole (DIP) is a vasodilator and antithrombotic drug.

Neuroprotective Effects of Guanosine Administration on In Vivo Cortical Focal Ischemia in Female and Male Wistar Rats.

Guanosine (GUO) has neuroprotective effects in experimental models of brain diseases involving glutamatergic excitotoxicity in male animals; however, its effects in female animals are poorly understood. Thus, we investigated the influence of gender and GUO treatment in adult male and female Wistar rats submitted to focal permanent cerebral ischemia in the motor cortex brain. Female rats were subdivided into non-estrogenic and estrogenic phase groups by estrous cycle verification.

Chronic Mild Hyperhomocysteinemia Alters Inflammatory and Oxidative/Nitrative Status and Causes Protein/DNA Damage, as well as Ultrastructural Changes in Cerebral Cortex: Is Acetylsalicylic Acid Neuroprotective?

Homocysteine is a sulfur-containing amino acid derived from methionine metabolism. When plasma homocysteine levels exceed 10-15 μM, there is a condition known as hyperhomocysteinemia, which occur as a result of an inborn error of methionine metabolism or by non-genetic causes. Mild hyperhomocysteinemia is considered a risk factor for development of neurodegenerative diseases.

Methionine Administration in Pregnant Rats Causes Memory Deficit in the Offspring and Alters Ultrastructure in Brain Tissue.

In the present work, we evaluated the effect of gestational hypermethioninemia on locomotor activity, anxiety, memory, and exploratory behavior of rat offspring through the following behavior tests: open field, object recognition, and inhibitory avoidance. Histological analysis was also done in the brain tissue of pups. Wistar female rats received methionine (2.

Effect of u18666a on beta-glucosidase, sphingomyelinase, and beta-galactosidase activities in astrocytes of young rats.

Niemann-Pick type C disease (NPC) is a neurodegenerative genetic disorder caused by accumulation of lipids, especially cholesterol, in the perinuclear space. U18666A is a cholesterol transport-inhibiting agent, being used to mimic NPC, mainly in fibroblasts. The objective of this study was to observe the effect of the drug U18666A, which causes the accumulation of cholesterol in the cytoplasm of astrocytes from newborn rats, on some lysosomal hydrolase activities.

Obesity associated with type 2 diabetes mellitus is linked to decreased PC1/3 mRNA expression in the Jejunum.

Background: Bariatric surgery is the most effective therapeutic option for obesity and its complications, especially in type 2 diabetes. The aim of this study was to investigate the messenger RNA (mRNA) gene expression of proglucagon, glucose-dependent insulinotropic peptide (GIP), prohormone convertase 1/3 (PC1/3), and dipeptidyl peptidase-IV (DPP-IV) in jejunum cells of the morbidly obese (OB) non type 2 diabetes mellitus (NDM2) and type 2 diabetes mellitus (T2DM), to determine the molecular basis of incretin secretion after bariatric surgery.

Methods: Samples of jejunal mucosa were obtained from 20 NDM2 patients: removal of a section of the jejunum about 60 cm distal to the ligament of Treitz and 18 T2DM patients: removal of a section of the jejunum about 100 cm distal to the ligament of Treitz.

Parallel down-regulation of FOXO1, PPARγ and adiponectin mRNA expression in visceral adipose tissue of class III obese individuals.

Objective: Adipose tissue is responsible for secretion of several cytokines that mediate systemic effects on obesity and insulin resistance. Subcutaneous abdominal adipose tissue (SAT) and visceral adipose tissue (VAT) are metabolically different and have differences in their gene expression profile. Our study evaluated the expression of adiponectin, FOXO1, PPARγ, and SIRT1 in VAT and SAT of non-obese and class III obese subjects.

Resveratrol upregulated SIRT1, FOXO1, and adiponectin and downregulated PPARγ1-3 mRNA expression in human visceral adipocytes.

Background: The SIRT1 enzyme is involved in adipose tissue (AT) lipolysis. FOXO1 is a protein that plays a significant role in regulating metabolism. Adiponectin is an adipokine, secreted by the AT, which has been considered to have an antiobesity function.