Sustained hippocampal IL-1β overexpression impairs contextual and spatial memory in transgenic mice

Hein, Amy M.; Stasko, Melissa R.; Matousek, Sarah B.; Scott-McKean, Jonah J.; Maier, Steven F.; Olschowka, John A.; Costa, Alberto C. S.; O’Banion, M. Kerry

doi:10.1016/j.bbi.2009.10.002

Cited by 200 publications

(163 citation statements)

References 37 publications

Supporting

Mentioning

145

Contrasting

Order By: Relevance

“…Specifically focusing on IL-1␤, impairments in long-term contextual and spatial memory were observed in a transgenic model of IL-1␤ overexpression. These impairments were accompanied by increased numbers of microglia and astrocytes, as well as increases in mRNA expression of several inflammatory markers (Hein et al, 2010). It is clearly evident from these studies and others that there is significant crosstalk between the immune and neural systems which permits inflammatory-mediated effects on neurogenesis and cognition.…”

Section: Adult Hippocampal Neurogenesis and Inflammationmentioning

confidence: 76%

Exercise as a pro-cognitive, pro-neurogenic and anti-inflammatory intervention in transgenic mouse models of Alzheimer’s disease

Ryan

Kelly

2016

Ageing Research Reviews

View full text Add to dashboard Cite

a b s t r a c tIt is now well established, at least in animal models, that exercise elicits potent pro-cognitive and proneurogenic effects. Alzheimer's disease (AD) is one of the leading causes of dementia and represents one of the greatest burdens on healthcare systems worldwide, with no effective treatment for the disease to date. Exercise presents a promising non-pharmacological option to potentially delay the onset of or slow down the progression of AD. Exercise interventions in mouse models of AD have been explored and have been found to reduce amyloid pathology and improve cognitive function. More recent studies have expanded the research question by investigating potential pro-neurogenic and anti-inflammatory effects of exercise. In this review we summarise studies that have examined exercise-mediated effects on AD pathology, cognitive function, hippocampal neurogenesis and neuroinflammation in transgenic mouse models of AD. Furthermore, we attempt to identify the optimum exercise conditions required to elicit the greatest benefits, taking into account age and pathology of the model, as well as type and duration of exercise.© 2016 Elsevier B.V. All rights reserved. Please cite this article in press as: Ryan, S.M., Kelly, Á.M., Exercise as a pro-cognitive, pro-neurogenic and anti-inflammatory intervention in transgenic mouse models of Alzheimer's disease. Ageing Res. Rev. (2016), http://dx

show abstract

Section: Adult Hippocampal Neurogenesis and Inflammationmentioning

confidence: 76%

Exercise as a pro-cognitive, pro-neurogenic and anti-inflammatory intervention in transgenic mouse models of Alzheimer’s disease

Ryan

Kelly

2016

Ageing Research Reviews

View full text Add to dashboard Cite

show abstract

“…Investigations into the mechanisms underlying these inflammatory processes have illustrated that proinflammatory cytokines induce an impairment in hippocampal-dependent memory (Barrientos et al, 2002;Hein et al, 2010) and LTP Curran and O'Connor, 2001). Additionally, inflammatory challenges associated with age, ␤-amyloid, or lipopolysaccharide (LPS) elicit similar deficits in LTP through activation of stress-activated protein kinases Kelly et al, 2003;Minogue et al, 2003;Costello and Herron, 2004;Barry et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

Interleukin-1α and HMGB1 Mediate Hippocampal Dysfunction in SIGIRR-Deficient Mice

Costello¹,

Watson²,

Cowley³

et al. 2011

J. Neurosci.

View full text Add to dashboard Cite

Single-Ig-interleukin-1 related receptor (SIGIRR) is a member of the interleukin (IL)-1/Toll-like receptor (TLR) family. It negatively regulates inflammation, rendering SIGIRRϪ/Ϫ mice more susceptible to inflammatory challenge. This susceptibility extends to the brain, where increased responsiveness to lipopolysaccharide has been observed in SIGIRR-deficient mice. While this is likely due to enhanced TLR4-mediated signaling, the functional consequences of these changes have not yet been described. In the current study, we have investigated the impact of SIGIRR deficiency on hippocampal function, and show that novel object recognition, spatial reference memory, and long-term potentiation (LTP) were impaired in SIGIRR Ϫ/Ϫ mice. These changes were accompanied by increased expression of IL-1RI and TLR4, and upregulation of their downstream signaling events, namely IRAK1 (IL-1R-associated kinase 1), c-Jun N-terminal protein kinase (JNK), and nuclear factor B (NF-B). The deficit in LTP was attenuated by the endogenous IL-1 receptor antagonist (IL-1ra) and an anti-TLR4 antibody, and also by inhibition of JNK and NF-B. We propose that IL-1RI is activated by IL-1␣ and TLR4 is activated by the endogenous agonist, high mobility group box 1 (HMGB1), as we identified enhanced expression of both cytokines in the hippocampus of SIGIRRϪ/Ϫ mice. Additionally, application of HMGB1 increased the activation of JNK and NF-B and was found to be detrimental to LTP in a TLR4-dependent manner. These findings highlight the functional role of SIGIRR in regulating inflammatorymediated synaptic and cognitive decline, and describe evidence of the key role of HMGB1 in this process.

show abstract

“…For example, peripheral LPS injection impaired spatial working memory [29] and hippocampal IL-1 impaired spatial memory recall [32]. Therefore, inflammation in the HPC associated with RSD may reduce hippocampus-dependent memory functions.…”

Section: Rsd Impaired Working Memory In the Morris Water Mazementioning

confidence: 99%

Repeated social defeat stress induces neuroinflammation and impairs hippocampal neurogenesis that differentially regulate mood and cognition

Niraula

McKim

Tarr

et al. 2015

Brain, Behavior, and Immunity

View full text Add to dashboard Cite

Repeated social defeat (RSD) is a murine stressor that models several key physiological, immunological, and behavioral alterations observed in humans exposed to psychosocial stress.RSD induces prolonged anxiety-like behavior associated with myeloid cell trafficking into the brain, including the hippocampus. Because the hippocampus (HPC) is a key area involved in neuroplasticity, behavior, and cognition, the goal of this study was to investigate if the stressinduced monocyte trafficking affected hippocampal neurogenesis and cognitive function. Here, we show that RSD increased inflammatory mediators (IL-1β, TNFα and IL-6), enhanced microglia activation and monocyte trafficking (CD45hi) specifically in the caudal hippocampus.RSD also impaired spatial memory recall in the Barnes maze independent of anxiety-like behavior. RSD did not affect the number of proliferating neural progenitor cells and developing neurons when examined 14 hours post-RSD. Nonetheless there was a significant reduction in the number of young neurons and mature neurons in the HPC 10 days and 28 days post-RSD, respectively. Consistent with region-specific neuroinflammation, reduction in the number of mature neurons was greater in the caudal hippocampus of the RSD mice compared to controls.The RSD-induced spatial deficits, which are rostral hippocampus-mediated, were resolved by 28 days. Social avoidance which is caudal hippocampus-mediated still persisted 28 days after stress.Thus, stress-induced neuroinflammation is associated with reduced neuroplasticity, and the stress-induced affective and cognitive deficits are differentially associated with hippocampal neurogenesis.2

show abstract

Sustained hippocampal IL-1β overexpression impairs contextual and spatial memory in transgenic mice

Cited by 200 publications

References 37 publications

Exercise as a pro-cognitive, pro-neurogenic and anti-inflammatory intervention in transgenic mouse models of Alzheimer’s disease

Exercise as a pro-cognitive, pro-neurogenic and anti-inflammatory intervention in transgenic mouse models of Alzheimer’s disease

Interleukin-1α and HMGB1 Mediate Hippocampal Dysfunction in SIGIRR-Deficient Mice

Repeated social defeat stress induces neuroinflammation and impairs hippocampal neurogenesis that differentially regulate mood and cognition

Contact Info

Product

Resources

About