Neuroinflammation in the normal aging hippocampus

Barrientos, Ruth M.; Kitt, Meagan M.; Watkins, Linda R.; Maier, Steven F.

doi:10.1016/j.neuroscience.2015.03.007

Cited by 271 publications

(210 citation statements)

References 226 publications

(327 reference statements)

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“…Neurogenesis in the dentate gyrus (DG) was assessed via administration of the thymidine analogue bromodeoxyuridine (BrdU), which is incorporated into the DNA of dividing cells, as well as staining for doublecortin (DCX), a marker of newly born neurons. A decline in neurogenesis is commonly observed in aging, and studies have indicated that this decline is in part due to chronically activated microglia (Barrientos, Kitt, Watkins, & Maier, 2015; Norden et al, 2015). As a result, aged mice exhibit markedly reduced neurogenesis, as seen by decreased levels of BrdU + cells ( p < 0.001, Figure 5b,d–e) and DCX staining ( p < 0.001, Figure 5b,e–f) in the subgranular zone (SGZ) of the DG compared to young mice.…”

Section: Resultsmentioning

confidence: 99%

“…As microglia mediate neuroinflammatory responses through the production of a variety of signaling molecules, including cytokines and chemokines, which can themselves modulate cognition (Barrientos et al, 2015; Patterson, 2015), we sought to explore changes in inflammatory‐related genes with microglial repopulation in aging. We found that microglial replacement in the aged brain did not affect expression of immune signaling molecules, either at basal levels or in response to a peripheral LPS challenge.…”

Section: Discussionmentioning

confidence: 99%

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Replacement of microglia in the aged brain reverses cognitive, synaptic, and neuronal deficits in mice

et al. 2018

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Microglia, the resident immune cell of the brain, can be eliminated via pharmacological inhibition of the colony‐stimulating factor 1 receptor (CSF1R). Withdrawal of CSF1R inhibition then stimulates microglial repopulation, effectively replacing the microglial compartment. In the aged brain, microglia take on a “primed” phenotype and studies indicate that this coincides with age‐related cognitive decline. Here, we investigated the effects of replacing the aged microglial compartment with new microglia using CSF1R inhibitor‐induced microglial repopulation. With 28 days of repopulation, replacement of resident microglia in aged mice (24 months) improved spatial memory and restored physical microglial tissue characteristics (cell densities and morphologies) to those found in young adult animals (4 months). However, inflammation‐related gene expression was not broadly altered with repopulation nor the response to immune challenges. Instead, microglial repopulation resulted in a reversal of age‐related changes in neuronal gene expression, including expression of genes associated with actin cytoskeleton remodeling and synaptogenesis. Age‐related changes in hippocampal neuronal complexity were reversed with both microglial elimination and repopulation, while microglial elimination increased both neurogenesis and dendritic spine densities. These changes were accompanied by a full rescue of age‐induced deficits in long‐term potentiation with microglial repopulation. Thus, several key aspects of the aged brain can be reversed by acute noninvasive replacement of microglia.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Replacement of microglia in the aged brain reverses cognitive, synaptic, and neuronal deficits in mice

et al. 2018

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“…In all ages, BDNF is involved in promoting the growth and maintenance of several neuronal systems as well as its involvement in functions of neuronal plasticity. The hippocampus and prefrontal cortex are most susceptible to aging, which causes the problems with cognitive function and memory [20]. BDNF, as a neurotrophic factor has been shown to be severely affected in the aging process and is associated with the decline of cognitive function [21].…”

Section: Discussionmentioning

confidence: 99%

Impact of the Dietary Supplement CLOCK® on BDNF and Other Biochemical Measures Related to Cognitive Function and Health in Men and Women

Bloomer

2017

ACIM

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Background: We have previously reported improvements in selected biochemical measures of health, as well as self reported well-being in men and women using the dietary supplement known as CLOCK ® . In this follow up investigation, we evaluated CLOCK ® at two different dosages using a randomized, placebo controlled, cross-over design in men and women with self reported low energy, impaired sleep quality and impaired well-being.Methods: 30 subjects (14 men and 16 women) were randomly assigned in double blind manner to ingest a botanical agent (CLOCK ® , containing Rosmarinus officinalis and Hemerocallis fulva at either 1gram or 1.5grams daily) or a placebo for two week periods with a two week wash out period after each condition assignment. Blood samples were collected pre and post each two week period in an overnight fasted state and analyzed for acetylcholine (ACh), choline, Brain Derived Neurotrophic Factor (BDNF), IGF-1, irisin, melatonin and serotonin. Heart rate and blood pressure were measured, as were subjective measures of well-being. The Leeds Sleep Evaluation Questionnaire was used as a measure of sleep quality and related variables.Results: ACh (22%), choline (19%), BDNF (44%), irisin (23%) and melatonin (8%) all increased significantly from pre to post intervention following intake of CLOCK ® (with a greater increase noted with 1gram vs. 1.5grams) but not placebo. Heart rate and blood pressure were unaffected by treatment (p>0.05). Time effects were noted for all well-being measures (p<0.05), except for anxious, depressed and tense, with improvements noted in all variables from pre to post intervention. When considering both supplement dosages together, improvements of 25% (attentiveness), 21% (alertness), 37% (focus) and 34% (energetic) were observed, with slightly less improvement noted for placebo. Although, not significant, CLOCK ® reduced the feeling of grogginess (25%), lethargy (14%) and sluggishness (18%); whereas there were minimal changes with the placebo. No differences were noted between conditions or across time in measures of sleep or related variables (p>0.05).

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“…IL-1β, IL-6 and TNFα), chemokines, nitric oxide (NO), eicosanoids (i.e. PGE2) and reactive oxygen species (ROS) (Barrientos et al, 2015;Vauzour, 2012). For example, increased level of IL-1β elevates the production of ROS, which in turn, activates mitogen-activated protein (MAP) kinases such as c-Jun N-terminal kinase (JNK) and p38, resulting in cell damage and cell death therefore impairing the long-term potentiation (LTP) and leading to cognitive decline.…”

Section: Introductionmentioning

confidence: 99%

“…For example, increased level of IL-1β elevates the production of ROS, which in turn, activates mitogen-activated protein (MAP) kinases such as c-Jun N-terminal kinase (JNK) and p38, resulting in cell damage and cell death therefore impairing the long-term potentiation (LTP) and leading to cognitive decline. In addition, the excessive production of pro-inflammatory cytokines such as TNFα and IL-1β has been reported to result in glutamate cytotoxicity by directly stimulating NMDA receptors while inhibiting gamma-aminobutyric acid (GABA)-A receptors (Barrientos et al, 2015;Olmos and Llado, 2014).…”

Section: Introductionmentioning

confidence: 99%

N-3 PUFAs and neuroinflammatory processes in cognitive disorders

Leyrolle

Layé

Nadjar

2016

OCL

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-With the ageing population and increased cases of neurodegenerative diseases, there is a crucial need for the development of new nutritional approaches to prevent and delay the onset of cognitive decline. Neuroinflammatory processes contribute to neuronal damage that underpins neurodegenerative disorders. Growing evidence sheds light on the use of dietary n-3 long chain polyunsaturated fatty acids to improve cognitive performances and reduce the neuroinflammatory responses occurring with age and neurodegenerative pathologies. This review will summarise the most recent information related to the impact and mechanisms underlying the neuroinflammatory processes in cognitive disorders. We will also discuss the mechanisms underlying n-3 polyunsaturated fatty acids effect on neuroinflammation and memory decline.Keywords: Neuroinflammation / microglia / n-3 polyunsaturated fatty acids / cognitive disorders / Alzheimer disease Résumé -Acides gras polyinsaturés de la famille des oméga 3, processus neuroinflammatoires et troubles cognitifs. Le développement d'approches nutritionnelles pertinentes pour prévenir et retarder l'apparition du déclin cognitif est un enjeu important, compte tenu du vieillissement de la population et de l'augmentation de l'incidence des maladies neurodégénératives. Les processus neuro-inflammatoires contribuent aux mécanismes neuropathologiques impliqués dans les troubles neurodégénératifs et de la cognition. Des données récentes indiquent l'importance des acides gras polyinsaturés n-3 alimentaires dans le maintien des performances mnésiques et la régulation de la neuroinflammation liée à l'âge ou à la maladie d'Alzheimer. Dans cette revue, seront présentées des données récentes sur les liens existants entre le statut nutritionnel en acides gras polyinsaturés n-3, les processus neuro-inflammatoires et les troubles cognitifs associés, ainsi que les mécanismes qui pourraient être impliqués dans les effets protecteurs de ces acides gras.

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Neuroinflammation in the normal aging hippocampus

Cited by 271 publications

References 226 publications

Replacement of microglia in the aged brain reverses cognitive, synaptic, and neuronal deficits in mice

Replacement of microglia in the aged brain reverses cognitive, synaptic, and neuronal deficits in mice

Impact of the Dietary Supplement CLOCK® on BDNF and Other Biochemical Measures Related to Cognitive Function and Health in Men and Women

N-3 PUFAs and neuroinflammatory processes in cognitive disorders

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