Lipids and brain inflammation in APOE4-associated dementia

Alzheimer’s disease is the most common form of dementia. It is characterized by betaamyloid peptide fibrils which are extracellular deposition of a specific protein, accompanied by extensive neuroinflammation. Various studies show the presence of a number of inflammation markers in the AD brain: elevated inflammatory cytokines and chemokines, and an accumulation of activated microglia in the damaged regions. NF-κB is a family of redox sensitive transcriptional factors, and it is known that NF-κB has binding sites in the promoter region of the genes involved in amyloidogenesis and inflammation. Long-term use of non-steroidal anti-inflammatory drugs prevents progression of AD and delays its onset, suggesting that there is a close correlation between NF-κB and AD pathogenesis. This study aims to (1) assess the association between NF-κB activity and AD through discussion of a variety of experimental and clinical studies on AD and (2) review treatment strategies designed to treat or prevent AD with NF-κB inhibitors.

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The effects of anaesthetics and sedatives on brain inflammation

Neuroscience & Biobehavioral Reviews ◽

10.1016/j.neubiorev.2021.05.009 ◽

2021 ◽

Author(s):

Diogo Dominguini ◽

Amanda V. Steckert ◽

Monique Michels ◽

Mariana B. Spies ◽

Cristiane Ritter ◽

...

Keyword(s):

Brain Inflammation

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G Protein-Coupled Estrogen Receptor 1 (GPER) as a Novel Target for Schizophrenia Drug Treatment

Schizophrenia Bulletin Open ◽

10.1093/schizbullopen/sgaa062 ◽

2020 ◽

Vol 1 (1) ◽

Author(s):

Danielle S Macêdo ◽

Lia Lira Olivier Sanders ◽

Raimunda das Candeias ◽

Cyntia de Freitas Montenegro ◽

David Freitas de Lucena ◽

...

Keyword(s):

Estrogen Receptor ◽

Estrogen Receptors ◽

G Protein ◽

Brain Inflammation ◽

Antipsychotic Treatment ◽

New Class ◽

Estrogen Receptor Modulators ◽

Novel Target ◽

G Protein Coupled ◽

Estrogen Receptor 1

Abstract The observation that a person’s sex influences the onset age of schizophrenia, the course of the disease, and antipsychotic treatment response suggests a possible role for estrogen receptors in the pathophysiology of schizophrenia. Indeed, treatment with adjunctive estrogen or selective estrogen receptor modulators (SERMs) are known to reduce schizophrenia symptoms. While estrogen receptors (ER)α and ERβ have been studied, a third and more recently discovered estrogen receptor, the G protein-coupled estrogen receptor 1 (GPER), has been largely neglected. GPER is a membrane receptor that regulates non-genomic estrogen functions, such as the modulation of emotion and inflammatory response. This review discusses the possible role of GPER in brain impairments seen in schizophrenia and in its potential as a therapeutic target. We conducted a comprehensive literature search in the PubMed/MEDLINE database, using the following search terms: “Schizophrenia,” “Psychosis,” “GPER1 protein,” “Estrogen receptors,” “SERMS,” “GPER1 agonism, “Behavioral symptoms,” “Brain Inflammation.” Studies involving GPER in schizophrenia, whether preclinical or human studies, have been scarce, but the results are encouraging. Agonism of the GPER receptor could prove to be an essential mechanism of action for a new class of “anti-schizophrenia” drugs.

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Induced Pluripotent Stem Cell-Derived Neural Precursors Improve Memory, Synaptic and Pathological Abnormalities in a Mouse Model of Alzheimer’s Disease

Cells ◽

10.3390/cells10071802 ◽

2021 ◽

Vol 10 (7) ◽

pp. 1802

Author(s):

Enrique Armijo ◽

George Edwards ◽

Andrea Flores ◽

Jorge Vera ◽

Mohammad Shahnawaz ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Clinical Symptoms ◽

Memory Loss ◽

Amyloid Β ◽

Cerebral Atrophy ◽

Brain Inflammation ◽

Neural Precursors ◽

Model Of Alzheimer’S Disease ◽

Induced Pluripotent

Alzheimer’s disease (AD) is the most common type of dementia in the elderly population. The disease is characterized by progressive memory loss, cerebral atrophy, extensive neuronal loss, synaptic alterations, brain inflammation, extracellular accumulation of amyloid-β (Aβ) plaques, and intracellular accumulation of hyper-phosphorylated tau (p-tau) protein. Many recent clinical trials have failed to show therapeutic benefit, likely because at the time in which patients exhibit clinical symptoms the brain is irreversibly damaged. In recent years, induced pluripotent stem cells (iPSCs) have been suggested as a promising cell therapy to recover brain functionality in neurodegenerative diseases such as AD. To evaluate the potential benefits of iPSCs on AD progression, we stereotaxically injected mouse iPSC-derived neural precursors (iPSC-NPCs) into the hippocampus of aged triple transgenic (3xTg-AD) mice harboring extensive pathological abnormalities typical of AD. Interestingly, iPSC-NPCs transplanted mice showed improved memory, synaptic plasticity, and reduced AD brain pathology, including a reduction of amyloid and tangles deposits. Our findings suggest that iPSC-NPCs might be a useful therapy that could produce benefit at the advanced clinical and pathological stages of AD.

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Supplementation with ribonucleotide-based ingredient (Ribodiet®) lessens oxidative stress, brain inflammation, and amyloid pathology in a murine model of Alzheimer

Biomedicine & Pharmacotherapy ◽

10.1016/j.biopha.2021.111579 ◽

2021 ◽

Vol 139 ◽

pp. 111579

Author(s):

Anella Saviano ◽

Gian Marco Casillo ◽

Federica Raucci ◽

Alessia Pernice ◽

Cristina Santarcangelo ◽

...

Keyword(s):

Oxidative Stress ◽

Murine Model ◽

Brain Inflammation ◽

Amyloid Pathology

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Schizophrenia linked to brain inflammation

The New Scientist ◽

10.1016/s0262-4079(15)31455-x ◽

2015 ◽

Vol 228 (3044) ◽

pp. 17

Keyword(s):

Brain Inflammation

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Pioglitazone Ameliorates Lipopolysaccharide-Induced Behavioral Impairment, Brain Inflammation, White Matter Injury and Mitochondrial Dysfunction in Neonatal Rats

International Journal of Molecular Sciences ◽

10.3390/ijms22126306 ◽

2021 ◽

Vol 22 (12) ◽

pp. 6306

Author(s):

Jiann-Horng Yeh ◽

Kuo-Ching Wang ◽

Asuka Kaizaki ◽

Jonathan W. Lee ◽

Han-Chi Wei ◽

...

Keyword(s):

Lipid Peroxidation ◽

White Matter ◽

Brain Inflammation ◽

White Matter Injury ◽

Neonatal Rat ◽

Mitochondrial Activity ◽

Neonatal Rats ◽

Activated Microglia ◽

Brain White Matter ◽

Performance Reduction

Previous studies have demonstrated that pioglitazone, a peroxisome proliferator-activated receptor gamma (PPARγ) agonist, inhibits ischemia-induced brain injury. The present study was conducted to examine whether pioglitazone can reduce impairment of behavioral deficits mediated by inflammatory-induced brain white matter injury in neonatal rats. Intraperitoneal (i.p.) injection of lipopolysaccharide (LPS, 2 mg/kg) was administered to Sprague–Dawley rat pups on postnatal day 5 (P5), and i.p. administration of pioglitazone (20 mg/kg) or vehicle was performed 5 min after LPS injection. Sensorimotor behavioral tests were performed 24 h after LPS exposure, and changes in biochemistry of the brain was examined after these tests. The results show that systemic LPS exposure resulted in impaired sensorimotor behavioral performance, reduction of oligodendrocytes and mitochondrial activity, and increases in lipid peroxidation and brain inflammation, as indicated by the increment of interleukin-1β (IL-1β) levels and number of activated microglia in the neonatal rat brain. Pioglitazone treatment significantly improved LPS-induced neurobehavioral and physiological disturbances including the loss of body weight, hypothermia, righting reflex, wire-hanging maneuver, negative geotaxis, and hind-limb suspension in neonatal rats. The neuroprotective effect of pioglitazone against the loss of oligodendrocytes and mitochondrial activity was associated with attenuation of LPS-induced increment of thiobarbituric acid reactive substances (TBARS) content, IL-1β levels and number of activated microglia in neonatal rats. Our results show that pioglitazone prevents neurobehavioral disturbances induced by systemic LPS exposure in neonatal rats, and its neuroprotective effects are associated with its impact on microglial activation, IL-1β induction, lipid peroxidation, oligodendrocyte production and mitochondrial activity.

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