Layer V cortical neurons require microglial support for survival during postnatal development

Ueno, Masaki; Fujita, Yuki; Tanaka, Tatsuhide; Nakamura, Yuka; Kikuta, Junichi; Ishii, Masaru; Yamashita, Toshio

doi:10.1038/nn.3358

Cited by 643 publications

(568 citation statements)

References 48 publications

Supporting

Mentioning

556

Contrasting

Unclassified

Order By: Relevance

“…Microglia numbers are elevated during the period of synaptic pruning in development, and following this, microglia numbers then fall to those found in the adult mouse brain (Nikodemova et al, 2015). Microglia during development also control neuronal survival and proliferation (Aarum, Sandberg, Haeberlein, & Persson, 2003; Ueno et al, 2013). Our results show that the elimination and reintroduction of microglia to the aged brain also have marked and parallel effects on neurogenesis, neuronal morphologies/circuitries, and synaptic and behavioral function.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2018

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionmentioning

confidence: 99%

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

et al. 2018

View full text Add to dashboard Cite

show abstract

“…For example, it was shown that microglia-derived insulin-like growth factor 1 was required for survival of layer V cortical neurons during the first week of postnatal life [21]. In addition, deletion of the fractalkine receptor, CX3CR1, which is enriched in microglia versus other resident brain cell types, resulted in delayed maturation of hippocampal synapses and abnormal circuit connectivity in adult mice [22,23].…”

Section: The Role Of Microglia In Cns Developmentmentioning

confidence: 99%

Neuroinflammation: Ways in Which the Immune System Affects the Brain

et al. 2015

View full text Add to dashboard Cite

Neuroinflammation is the response of the central nervous system (CNS) to disturbed homeostasis and typifies all neurological diseases. The main reactive components of the CNS include microglial cells and infiltrating myeloid cells, astrocytes, oligodendrocytes, and the blood-brain b a r r i e r , c y t o k i n e s , a n d c y t o k i n e s i g n a l i n g . Neuroinflammatory responses may be helpful or harmful, as mechanisms associated with neuroinflammation are involved in normal brain development, as well as in neuropathological processes. This review examines the roles of various cell types that contribute to the immune dysregulation associated with neuroinflammation. Microglia enter the CNS very early in embryonic development and, as such, play an essential role in both the healthy and diseased brain. B-cell diversity contributes to CNS disease through both antibody-dependent and antibody-independent mechanisms. The influences of these B-cell mechanisms on other cell types, including myeloid cells and T cells, are reviewed in relationship to antibody-mediated CNS disorders, paraneoplastic neurological diseases, and multiple sclerosis. New insights into neuroinflammation offer exciting opportunities to investigate potential therapeutic targets for debilitating CNS diseases.

show abstract

“…18 Likewise, numerous studies have demonstrated microglia's own biological identity including the regulation of synaptic pruning and plasticity, [42][43][44] the spatial distribution of axonal projections, 45,46 and neuronal homeostasis and survival. 47,48 Alternatively, a current hypothesis proposes that microglial reactivity may be stimulated by damaged neurons with deficient signaling, the presence of circulatory plasma molecules in the CNS due to the BBB disruption, and peripheral leukocyte signaling mediated by cytokines after interactions with microbes or their antigens. 24 Major efforts in specifically dissecting the biology of microglia should focused on using epigenomics, comparative transcriptomics, proteomics, and other multidimensional technologies such as computational biology and 2-photon imaging.…”

Section: States Of Existencementioning

confidence: 99%

Role of microglia in fungal infections of the central nervous system

2016

View full text Add to dashboard Cite

Most fungi are capable of disseminating into the central nervous system (CNS) commonly being observed in immunocompromised hosts. Microglia play a critical role in responding to these infections regulating inflammatory processes proficient at controlling CNS colonization by these eukaryotic microorganisms. Nonetheless, it is this inflammatory state that paradoxically yields cerebral mycotic meningoencephalitis and abscess formation. As peripheral macrophages and fungi have been investigated aiding our understanding of peripheral disease, ascertaining the key interactions between fungi and microglia may uncover greater abilities to treat invasive fungal infections of the brain. Here, we present the current knowledge of microglial physiology. Due to the existing literature, we have described to greater extent the opportunistic mycotic interactions with these surveillance cells of the CNS, highlighting the need for greater efforts to study other cerebral fungal infections such as those caused by geographically restricted dimorphic and rare fungi.

show abstract

Layer V cortical neurons require microglial support for survival during postnatal development

Cited by 643 publications

References 48 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

Neuroinflammation: Ways in Which the Immune System Affects the Brain

Role of microglia in fungal infections of the central nervous system

Contact Info

Product

Resources

About