Neuroinflammation negatively affects adult hippocampal neurogenesis and cognition: can exercise compensate?

Ryan, Sinead M.; Nolan, Yvonne M.

doi:10.1016/j.neubiorev.2015.12.004

Cited by 157 publications

(98 citation statements)

References 131 publications

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“…Thus, A1-exosome treatment after SE eased aberrant neurogenesis via protection of reelin + interneurons, which is likely a result of repression of inflammation facilitated by A1-exosomes. Decreased inflammation and normal levels of neurogenesis likely also contributed to the preservation of cognitive and memory function in the SE-EVs group, as inflammation and decreased neurogenesis can impair cognitive and memory function (56,57). A series of object-based tests in the present study demonstrated the impaired ability of animals in the SE-VEH group for cognition and memory.…”

Section: Discussionmentioning

confidence: 55%

Intranasal MSC-derived A1-exosomes ease inflammation, and prevent abnormal neurogenesis and memory dysfunction after status epilepticus

Long

Upadhya

Hattiangady

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

324

299

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Status epilepticus (SE), a medical emergency that is typically terminated through antiepileptic drug treatment, leads to hippocampus dysfunction typified by neurodegeneration, inflammation, altered neurogenesis, as well as cognitive and memory deficits. Here, we examined the effects of intranasal (IN) administration of extracellular vesicles (EVs) secreted from human bone marrowderived mesenchymal stem cells (MSCs) on SE-induced adverse changes. The EVs used in this study are referred to as A1-exosomes because of their robust antiinflammatory properties. We subjected young mice to pilocarpine-induced SE for 2 h and then administered A1-exosomes or vehicle IN twice over 24 h. The A1-exosomes reached the hippocampus within 6 h of administration, and animals receiving them exhibited diminished loss of glutamatergic and GABAergic neurons and greatly reduced inflammation in the hippocampus. Moreover, the neuroprotective and antiinflammatory effects of A1-exosomes were coupled with long-term preservation of normal hippocampal neurogenesis and cognitive and memory function, in contrast to waned and abnormal neurogenesis, persistent inflammation, and functional deficits in animals receiving vehicle. These results provide evidence that IN administration of A1-exosomes is efficient for minimizing the adverse effects of SE in the hippocampus and preventing SE-induced cognitive and memory impairments.status epilepticus | memory dysfunction | neuroinflammation | exosomes | adult neurogenesis S tatus epilepticus (SE) is a grave medical crisis that requires swift remedy through all age groups (1, 2). It can produce substantial neurodegeneration, blood-brain barrier disruption, and inflammation in the hippocampus if not extinguished quickly by antiepileptic drug (AED) treatment (3-5). An episode of extended SE is sufficient to cause chronic hippocampus dysfunction, exemplified by persistent inflammation with activation of microglia and monocyte infiltration, loss of sizable fractions of several subclasses of inhibitory interneurons, aberrant and waned neurogenesis, hippocampus-dependent cognitive and memory impairments, and chronic epilepsy (5-12). Numerous situations such as head trauma, stroke, Alzheimer's disease, brain tumor, and encephalitis can engender SE. Although administration of AEDs leads to termination of SE in most instances, it does not thwart the evolution of SE into chronic epilepsy (13-16). A multitude of changes ensue in the hippocampus after an episode of SE, which evolve over a period of months, years, or even decades, and result in chronic epilepsy when they have reached certain thresholds (11,17,18). Hence, there is an urgent need to find an adjuvant therapy with AEDs that not only provides neuroprotection and suppression of inflammation in the early phase after SE but also maintains normal neurogenesis, preserves cognitive and memory function, and thwarts epilepsy development in the chronic phase after SE. The i.v. administration of bone marrow-derived mononuclear cells (MNCs) or mesenchymal stem cells (...

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Section: Discussionmentioning

confidence: 55%

Intranasal MSC-derived A1-exosomes ease inflammation, and prevent abnormal neurogenesis and memory dysfunction after status epilepticus

Long

Upadhya

Hattiangady

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

324

299

View full text Add to dashboard Cite

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“…Exercise exhibits systemic and end-organ anti-inflammatory effects as well as contributing to more efficient carbohydrate metabolism, in addition to trophic effects at the level of the central nervous system 6 7. In fact, increasing physical activity offers an effective treatment and preventative strategy for many chronic conditions in which the gut microbiome has been implicated 8–10.…”

Section: Introductionmentioning

confidence: 99%

The microbiome of professional athletes differs from that of more sedentary subjects in composition and particularly at the functional metabolic level

Barton

Penney

Cronin

et al. 2017

Gut

388

434

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“…The microarray results indicated there was differential expression of the genes involved in inflammation, immune response, development, cytoskeleton, and cell adhesion processes. We interpreted these results in the context of published findings indicating a relationship between increased expression of inflammation and immune response genes resulting in decreased neurogenesis, and impaired neurogenesis resulting in cognitive deficits [22,23,24,25,26,27]. From this framework, we then hypothesized that these changes in gene expression could indicate impaired neurogenesis resulting from the combination of alcohol and SIV.…”

Section: Discussionmentioning

confidence: 74%

“…These cells are found primarily in the subventricular zone and the hippocampus. We chose to further investigate the development process for several reasons: (1) the hippocampus is one of the primary sites of adult neurogenesis [20]; (2) alterations in adult neurogenesis have been linked to cognitive impairments [20,21]; (3) neuroinflammation alters neurogenesis [22,23,24]; and (4) experimentally impairing hippocampal neurogenesis results in learning and memory deficits [25,26,27]. Enhanced neuroinflammation, which is suggested by the microarray gene changes, alters neurogenesis.…”

Section: Introductionmentioning

confidence: 99%

Chronic Binge Alcohol Administration Dysregulates Hippocampal Genes Involved in Immunity and Neurogenesis in Simian Immunodeficiency Virus-Infected Macaques

et al. 2016

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Alcohol use disorders (AUD) exacerbate neurocognitive dysfunction in Human Immunodeficiency Virus (HIV+) patients. We have shown that chronic binge alcohol (CBA) administration (13–14 g EtOH/kg/wk) prior to and during simian immunodeficiency virus (SIV) infection in rhesus macaques unmasks learning deficits in operant learning and memory tasks. The underlying mechanisms of neurocognitive alterations due to alcohol and SIV are not known. This exploratory study examined the CBA-induced differential expression of hippocampal genes in SIV-infected (CBA/SIV+; n = 2) macaques in contrast to those of sucrose administered, SIV-infected (SUC/SIV+; n = 2) macaques. Transcriptomes of hippocampal samples dissected from brains obtained at necropsy (16 months post-SIV inoculation) were analyzed to determine differentially expressed genes. MetaCore from Thomson Reuters revealed enrichment of genes involved in inflammation, immune responses, and neurodevelopment. Functional relevance of these alterations was examined in vitro by exposing murine neural progenitor cells (NPCs) to ethanol (EtOH) and HIV trans-activator of transcription (Tat) protein. EtOH impaired NPC differentiation as indicated by decreased βIII tubulin expression. These findings suggest a role for neuroinflammation and neurogenesis in CBA/SIV neuropathogenesis and warrant further investigation of their potential contribution to CBA-mediated neurobehavioral deficits.

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Neuroinflammation negatively affects adult hippocampal neurogenesis and cognition: can exercise compensate?

Cited by 157 publications

References 131 publications

Intranasal MSC-derived A1-exosomes ease inflammation, and prevent abnormal neurogenesis and memory dysfunction after status epilepticus

Intranasal MSC-derived A1-exosomes ease inflammation, and prevent abnormal neurogenesis and memory dysfunction after status epilepticus

The microbiome of professional athletes differs from that of more sedentary subjects in composition and particularly at the functional metabolic level

Chronic Binge Alcohol Administration Dysregulates Hippocampal Genes Involved in Immunity and Neurogenesis in Simian Immunodeficiency Virus-Infected Macaques

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