scholarly journals Lupus antibodies induce behavioral changes mediated by microglia and blocked by ACE inhibitors

2018 ◽  
Vol 215 (10) ◽  
pp. 2554-2566 ◽  
Author(s):  
Jacquelyn Nestor ◽  
Yoshiyuki Arinuma ◽  
Tomás S. Huerta ◽  
Czeslawa Kowal ◽  
Elham Nasiri ◽  
...  
Keyword(s):  
Spatial Memory ◽  
Lupus Erythematosus ◽  
Memory Impairment ◽  
Neuronal Damage ◽  
Ace Inhibition ◽  
Neuronal Function ◽  
Nuclear Antigens ◽  
Dna Antibodies ◽  
Strong Candidate

Cognitive impairment occurs in 40–90% of patients with systemic lupus erythematosus (SLE), which is characterized by autoantibodies to nuclear antigens, especially DNA. We discovered that a subset of anti-DNA antibodies, termed DNRAbs, cross reacts with the N-methyl-d-aspartate receptor (NMDAR) and enhances NMDAR signaling. In patients, DNRAb presence associates with spatial memory impairment. In a mouse model, DNRAb-mediated brain pathology proceeds through an acute phase of excitotoxic neuron loss, followed by persistent alteration in neuronal integrity and spatial memory impairment. The latter pathology becomes evident only after DNRAbs are no longer detectable in the brain. Here we investigate the mechanism of long-term neuronal dysfunction mediated by transient exposure to antibody. We show that activated microglia and C1q are critical mediators of neuronal damage. We further show that centrally acting inhibitors of angiotensin-converting enzyme (ACE) can prevent microglial activation and preserve neuronal function and cognitive performance. Thus, ACE inhibition represents a strong candidate for clinical trials aimed at mitigating cognitive dysfunction.

Systemic Lupus Erythematosus

2019 ◽  
Author(s):  
Kyriakos A. Kirou ◽  
Michael D. Lockshin
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Sun Exposure ◽  
Disease Classification ◽  
Discoid Lupus Erythematosus ◽  
Neurologic Disease ◽  
Systemic Lupus ◽  
Nuclear Antigens ◽  
Key Words Systemic Lupus

Systemic lupus erythematosus (SLE) is a chronic systemic autoimmune illness characterized by autoantibodies directed at nuclear antigens that cause clinical and laboratory abnormalities, such as rash, arthritis, leukopenia and thrombocytopenia, alopecia, fever, nephritis, and neurologic disease. Most or all of the symptoms of acute lupus are attributable to immunologic attack on the affected organs. Many complications of long-term disease are attributable to both the disease and its treatment. Intense sun exposure, drug reactions, and infections are circumstances that induce flare; the aim of treatment is to induce remission. This chapter is divided into sections dealing with SLE’s definitions; epidemiology; pathogenesis; disease classification, diagnosis, and differential diagnosis; and treatment. This review contains 10 figures, 12 tables, and 97 references. Key Words: Systemic lupus erythematosus, Dermatomyositis, Sjögren syndrome, rheumatoid arthritis, systemic sclerosis, Discoid lupus erythematosus, truncal psoriasiform, annular polycyclic rash

Systemic Lupus Erythematosus

2019 ◽  
Author(s):  
Kyriakos A. Kirou ◽  
Michael D. Lockshin
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Sun Exposure ◽  
Disease Classification ◽  
Discoid Lupus Erythematosus ◽  
Neurologic Disease ◽  
Systemic Lupus ◽  
Nuclear Antigens ◽  
Key Words Systemic Lupus

Systemic lupus erythematosus (SLE) is a chronic systemic autoimmune illness characterized by autoantibodies directed at nuclear antigens that cause clinical and laboratory abnormalities, such as rash, arthritis, leukopenia and thrombocytopenia, alopecia, fever, nephritis, and neurologic disease. Most or all of the symptoms of acute lupus are attributable to immunologic attack on the affected organs. Many complications of long-term disease are attributable to both the disease and its treatment. Intense sun exposure, drug reactions, and infections are circumstances that induce flare; the aim of treatment is to induce remission. This chapter is divided into sections dealing with SLE’s definitions; epidemiology; pathogenesis; disease classification, diagnosis, and differential diagnosis; and treatment. This review contains 10 figures, 12 tables, and 97 references. Key Words: Systemic lupus erythematosus, Dermatomyositis, Sjögren syndrome, rheumatoid arthritis, systemic sclerosis, Discoid lupus erythematosus, truncal psoriasiform, annular polycyclic rash

Long-term combined administration of Bifidobacterium bifidum TMC3115 and Lactobacillus plantarum 45 alleviates spatial memory impairment and gut dysbiosis in APP/PS1 mice

2020 ◽  
Vol 367 (7) ◽  
Author(s):  
Feng Wang ◽  
Tong Xu ◽  
Yujie Zhang ◽  
Tingting Zheng ◽  
Yunling He ◽  
...  
Keyword(s):  
Spatial Memory ◽  
Lactobacillus Plantarum ◽  
Memory Impairment ◽  
Bifidobacterium Bifidum ◽  
Morris Water Maze Test ◽  
Gut Dysbiosis ◽  
Combined Use ◽  
Combined Administration ◽  
Group 1

ABSTRACT This study aimed to determine the effects of Bifidobacterium bifidum TMC3115, Lactobacillus plantarum 45 (LP45) and their combined use on cognitive performance and gut microbiota in APP/PS1 mice. The APP/PS1 mice were randomly divided into four groups: Alzheimer's disease (AD) model group, TMC3115 group [1 × 109 colony forming unit (CFU)], LP45 group (1 × 109 CFU) and a mixture group of TMC3115 (5 × 108 CFU) and LP45 (5 × 108 CFU). The wild-type littermates were chosen as normal control. The mice were sacrificed at the end of 22 weeks after behavioral evaluation. Collected cecum content was analyzed using 16S rRNA sequencing. Combined use of TMC3115 and LP45 significantly increased the times across the platform, time spent in the target quadrant compared with the AD, TMC3115 and LP45 groups in Morris water maze test. Microbiota analysis showed that combined TMC3115 and LP45 supplementation significantly increased observed species and beta diversity, and reversed gut dysbiosis by decreasing the abundance of Bacteroides and increasing the abundance of Acetatifactor and Millionella. These results indicate the long-term combined administration of TMC3115 and LP45 can improve spatial memory impairment in APP/PS1 mice and suggest that modifying the gut microbiome may provide potential benefits for AD patients.

scholarly journals Long-term hippocampal interneuronopathy drives sex-dimorphic spatial memory impairment induced by prenatal THC exposure

2020 ◽  
Vol 45 (5) ◽  
pp. 877-886 ◽  
Author(s):  
Adán de Salas-Quiroga ◽  
Daniel García-Rincón ◽  
Daniel Gómez-Domínguez ◽  
Manuel Valero ◽  
Samuel Simón-Sánchez ◽  
...  
Keyword(s):  
Spatial Memory ◽  
Memory Impairment

Systemic Lupus Erythematosus

2019 ◽  
Author(s):  
Kyriakos A. Kirou ◽  
Michael D. Lockshin
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Sun Exposure ◽  
Disease Classification ◽  
Discoid Lupus Erythematosus ◽  
Neurologic Disease ◽  
Systemic Lupus ◽  
Nuclear Antigens ◽  
Key Words Systemic Lupus

Systemic lupus erythematosus (SLE) is a chronic systemic autoimmune illness characterized by autoantibodies directed at nuclear antigens that cause clinical and laboratory abnormalities, such as rash, arthritis, leukopenia and thrombocytopenia, alopecia, fever, nephritis, and neurologic disease. Most or all of the symptoms of acute lupus are attributable to immunologic attack on the affected organs. Many complications of long-term disease are attributable to both the disease and its treatment. Intense sun exposure, drug reactions, and infections are circumstances that induce flare; the aim of treatment is to induce remission. This chapter is divided into sections dealing with SLE’s definitions; epidemiology; pathogenesis; disease classification, diagnosis, and differential diagnosis; and treatment. This review contains 10 figures, 12 tables, and 97 references. Key Words: Systemic lupus erythematosus, Dermatomyositis, Sjögren syndrome, rheumatoid arthritis, systemic sclerosis, Discoid lupus erythematosus, truncal psoriasiform, annular polycyclic rash

scholarly journals Regional Brain Metabolism in a Murine Systemic Lupus Erythematosus Model

2014 ◽  
Vol 34 (8) ◽  
pp. 1315-1320 ◽  
Author(s):  
An Vo ◽  
Bruce T Volpe ◽  
Chris C Tang ◽  
Wynne K Schiffer ◽  
Czeslawa Kowal ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Memory Impairment ◽  
Brain Metabolism ◽  
Imaging Data ◽  
Systemic Lupus ◽  
Murine Systemic Lupus Erythematosus ◽  
Dna Antibodies ◽  
Time Courses ◽  
Regional Metabolism

Systemic lupus erythematosus (SLE) is characterized by multiorgan inflammation, neuropsychiatric disorders (NPSLE), and anti-nuclear antibodies. We previously identified a subset of anti-DNA antibodies (DNRAb) cross-reactive with the N-methyl-D-aspartate receptor, present in 30% to 40% of patients, able to enhance excitatory post-synaptic potentials and trigger neuronal apoptosis. DNRAb + mice exhibit memory impairment or altered fear response, depending on whether the antibody penetrates the hippocampus or amygdala. Here, we used 18F-fluorodeoxyglucose (FDG) microPET to plot changes in brain metabolism after regional blood-brain barrier (BBB) breach. In DNRAb + mice, metabolism declined at the site of BBB breach in the first 2 weeks and increased over the next 2 weeks. In contrast, DNRAb — mice exhibited metabolic increases in these regions over the 4 weeks after the insult. Memory impairment was present in DNRAb + animals with hippocampal BBB breach and altered fear conditioning in DNRAb + mice with amygdala BBB breach. In DNRAb + mice, we observed an inverse relationship between neuron number and regional metabolism, while a positive correlation was observed in DNRAb — mice. These findings suggest that local metabolic alterations in this model take place through different mechanisms with distinct time courses, with important implications for the interpretation of imaging data in SLE subjects.

7,8-dihydroxyflavone, a TrkB receptor agonist, blocks long-term spatial memory impairment caused by immobilization stress in rats

Hippocampus ◽  
2010 ◽  
Vol 22 (3) ◽  
pp. 399-408 ◽  
Author(s):  
Raül Andero ◽  
Núria Daviu ◽  
Rosa Maria Escorihuela ◽  
Roser Nadal ◽  
Antonio Armario
Keyword(s):  
Spatial Memory ◽  
Memory Impairment ◽  
Receptor Agonist ◽  
Immobilization Stress ◽  
Trkb Receptor
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