Systemic Inflammation Induces Acute Behavioral and Cognitive Changes and Accelerates Neurodegenerative Disease

Cunningham, Colm; Campion, Suzanne; Lunnon, Katie; Murray, Carol; Woods, Jason; Deacon, Robert M. J.; Rawlins, J. N. P.; Perry, V. Hugh

doi:10.1016/j.biopsych.2008.07.024

Cited by 496 publications

(385 citation statements)

References 52 publications

(34 reference statements)

Supporting

Mentioning

360

Contrasting

Unclassified

Order By: Relevance

“…3). Evidence has shown that microglia exposed to systemic inflammatory stimuli have increased reactivity, leading to accelerated neuronal death and progression of CNS disease [189][190][191]. It has been suggested that primed microglia contribute to the increased response to a second inflammatory stimulus [192].…”

Section: Modulatory Function Of Mononuclear Phagocytes In Comorbiditiesmentioning

confidence: 99%

Microglia and Monocyte-Derived Macrophages in Stroke

2016

View full text Add to dashboard Cite

Historically, the brain has been considered an immune-privileged organ separated from the peripheral immune system by the blood-brain barrier. However, immune responses do occur in the brain in neurological conditions in which the integrity of the blood-brain barrier is compromised, exposing the brain to peripheral antigens and endogenous danger signals. While most of the associated pathological processes occur in the central nervous system, it is now clear that peripheral immune cells, especially mononuclear phagocytes, that infiltrate into the injury site play a key role in modulating the progression of primary brain injury development. As inflammation is a necessary and critical component for the subsequent injury resolution process, understanding the contribution of mononuclear phagocytes on the regulation of inflammatory responses may provide novel approaches for potential therapies. Furthermore, predisposed comorbid conditions at the time of stroke cause the alteration of stroke-induced immune and inflammatory responses and subsequently influence stroke outcome. In this review, we summarize a role for microglia and monocytes/macrophages in acute ischemic stroke in the context of normal and metabolically compromised conditions.

show abstract

Section: Modulatory Function Of Mononuclear Phagocytes In Comorbiditiesmentioning

confidence: 99%

Microglia and Monocyte-Derived Macrophages in Stroke

2016

View full text Add to dashboard Cite

show abstract

“…For this reason, LPS are commonly employed to mimic bacterial infections in experimental animals. The systemic inflammation mediated by the LPS can trigger a set of cellular and molecular events that are able to initiate neuroinflammation to affect cognitive function (Arai et al 2001;Cunningham et al 2009;Sparkman et al 2006) and reduce adult neurogenesis (Fujioka and Akema 2010;Monje et al 2003). It has been well documented that pregnant animals have an increased sensitivity to LPS compared to non-pregnant ones (Faas et al 2003;Kunnen et al 2014).…”

Section: Introductionmentioning

confidence: 99%

Inflammatory insult during pregnancy accelerates age-related behavioral and neurobiochemical changes in CD-1 mice

Wang

Chen

et al. 2016

AGE

View full text Add to dashboard Cite

Data shows that inflammation during pregnancy significantly exerts a long-term influence on offspring, such as increasing the risk of adult cognition decline in animals. However, it is unclear whether gestational inflammation affects the neurobehavioral and neurobiochemical outcomes in the motherself during aging. In this study, pregnant CD-1 mice intraperitoneally received lipopolysaccharide (LPS) in two doses (25 and 50 g/kg, respectively) or normal saline daily during gestational days 15-17. At the age of 15 months, a battery of behavioral tasks was employed to evaluate their species-typical behaviors, sensorimotor ability, anxiety levels, and spatial learning and memory abilities. An immunohistochemical method was utilized preliminarily to detect neurobiochemical indicators consisting of amyloid-β, p h o s p h o r y l a t e d t a u , p r e s y n a p t i c p r o t e i n s synaptotagmin-1 and syntaxin-1, glial fibrillary acidic protein (GFAP), and histone-4 acetylation on the K8 site (H4K8ac). The behavioral results showed that LPS exposure during pregnancy exacerbated a decline in 15-month-old CD-1 mice's abilities to nest, their sensorimotor and spatial learning and memory capabilities, and increased their anxiety levels. The neurobiochemical results indicated that gestational LPS exposure also intensified age-related hippocampal changes, including increased amyloid-β 42 , phosphorylated tau, synaptotagmin-1 and GFAP, and decreased syntaxin-1 and H4K8ac. Our results suggested that the inflammatory insult during pregnancy could be an important risk factor for the development of Alzheimer's disease, and the H4K8 acetylation might play an important role in the underlying mechanism. This study offers a perspective for improving strategies that support healthy development and successful aging.

show abstract

“…After the testing period, the remaining food in the cylinder was weighed and the mouse was returned to its collective cage. Burrowing is an ethological task highly sensitive to systemic inflammation (Cunningham et al 2009). …”

Section: Experimental Groups and Inoculation -mentioning

confidence: 99%

Environmental influences on antibody-enhanced dengue disease outcomes

Diniz

Fôro

Turiel³

et al. 2012

Mem. Inst. Oswaldo Cruz

Self Cite

View full text Add to dashboard Cite

Because an enriched environment (EE) enhances T-cell activity and T-lymphocytes contribute to immunopathogenesis during heterologous dengue virus (DENV) infections, we hypothesised that an EE increases dengue severity. To compare single serotype (SS) and antibody-enhanced disease (AED) infections regimens, serial intraperitoneal were performed with DENV3 (genotype III) infected brain homogenate or anti-DENV2 hyperimmune serum followed 24 h later by DENV3 (genotype III) infected brain homogenate. Compared AED for which significant differences were detected between the EE and impoverished environmental (IE) groups (Kaplan-Meyer log-rank test, p = 0.0025), no significant differences were detected between the SS experimental groups (Kaplan-Meyer log-rank test, p = 0.089). Survival curves from EE and IE animals infected with the AED regimen were extended after corticoid injection and this effect was greater in the EE than in the IE group (Kaplan-Meyer log-rank test, p = 0.0162). Under the AED regimen the EE group showed more intense clinical signs than the IE group. Dyspnoea, tremor, hunched posture, ruffled fur, immobility, pre-terminal paralysis, shock and death were associated with dominant T-lymphocytic hyperplasia and presence of viral antigens in the liver and lungs. We propose that the increased expansion of these memory T-cells and serotype cross-reactive antibodies facilitates the infection of these cells by DENV and that these events correlate with disease severity in an EE

show abstract

Systemic Inflammation Induces Acute Behavioral and Cognitive Changes and Accelerates Neurodegenerative Disease

Cited by 496 publications

References 52 publications

Microglia and Monocyte-Derived Macrophages in Stroke

Microglia and Monocyte-Derived Macrophages in Stroke

Inflammatory insult during pregnancy accelerates age-related behavioral and neurobiochemical changes in CD-1 mice

Environmental influences on antibody-enhanced dengue disease outcomes

Contact Info

Product

Resources

About