Microglial activation in the developing rat olfactory bulb

Fiske, Brian; Brunjes, Peter C.

doi:10.1016/s0306-4522(99)00601-6

Cited by 48 publications

(34 citation statements)

References 60 publications

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“…This suggests that (1) dying adult-born OB neurons in the healthy OB circuit do not substantially activate microglia, and (2) the continuous turnover of adult-born OB neurons does not depend on the activation state of microglia, although we cannot rule out that a low level of activation may be sufficient to clear normal levels of apoptosis. In contrast to our finding, it is noteworthy that substantial numbers of activated microglia have been reported in the developing OB (Fiske and Brunjes, 2000). Postnatal development is a period of broad neurogenesis within the OB, with precise pruning of excess neurons to allow correct tuning of neuronal circuits.…”

Section: Microglial Cells Mediate Innate Immune Responsecontrasting

confidence: 56%

Early Activation of Microglia Triggers Long-Lasting Impairment of Adult Neurogenesis in the Olfactory Bulb

Lazarini

Gabellec²,

Torquet³

et al. 2012

J. Neurosci.

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Microglia, the innate immune cells of the brain, engulf and eliminate cellular debris during brain injury and disease. Recent observations have extended their roles to the healthy brain, but the functional impact of activated microglia on neural plasticity has so far been elusive. To explore this issue, we investigated the role of microglia in the function of the adult olfactory bulb network in which both sensory afferents and local microcircuits are continuously molded by the arrival of adult-born neurons. We show here that the adult olfactory bulb hosts a large population of resident microglial cells. Deafferentation of the olfactory bulb resulted in a transient activation of microglia and a concomitant reduction of adult olfactory bulb neurogenesis. One day after sensory deafferentation, microglial cells proliferate in the olfactory bulb, and their numbers peaked at day 3, and reversed at day 7 after lesion. Similar lesions performed on immunodeficient mice demonstrate that the both innate and adaptive lymphocyte responses are dispensable for the lesion-induced microglial proliferation and activation. In contrast, when mice were treated with an antiinflammatory drug to prevent microglial activation, olfactory deafferentation did not reduce adult neurogenesis, showing that activated microglial cells per se, and not the lack of sensory experience, relates to the survival of adult-born neurons. We conclude that the status of the resident microglia in the olfactory bulb is an important factor directly regulating the survival of immature adult-born neurons.

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Section: Microglial Cells Mediate Innate Immune Responsecontrasting

confidence: 56%

Early Activation of Microglia Triggers Long-Lasting Impairment of Adult Neurogenesis in the Olfactory Bulb

Lazarini

Gabellec²,

Torquet³

et al. 2012

J. Neurosci.

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“…Postnatal microgliosis lasts for approximately 4 weeks in the rodent OB, then microglia gradually transform into a resting state and provide a constant surveillance system for the maintenance of normal brain functions [32]. However, our results suggest that persistent microgliosis develops in the NPC1-OB, which is also found in other brain regions [26].…”

Section: Discussionmentioning

confidence: 92%

Excessive microglial activation aggravates olfactory dysfunction by impeding the survival of newborn neurons in the olfactory bulb of Niemann–Pick disease type C1 mice

Seo

Kim

Shin

et al. 2014

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Diseas

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Progressive olfactory impairment is one of the earliest markers of neurodegeneration. However, the underlying mechanism for this dysfunction remains unclear. The present study investigated the possible role of microgliosis in olfactory deficits using a mouse model of Niemann-Pick disease type C1 (NPC1), which is an incurable neurodegenerative disorder with disrupted lipid trafficking. At 7weeks of age, NPC1 mutants showed a distinct olfactory impairment in an olfactory test compared with age-matched wild-type controls (WT). The marked loss of olfactory sensory neurons within the NPC1 affected olfactory bulb (NPC1-OB) suggests that NPC1 dysfunction impairs olfactory structure. Furthermore, the pool of neuroblasts in the OB was diminished in NPC1 mice despite the intact proliferative capacity of neural stem/progenitor cells in the subventricular zone. Instead, pro-inflammatory proliferating microglia accumulated extensively in the NPC1-OB as the disease progressed. To evaluate the impact of abnormal microglial activation on olfaction in NPC1 mice, a microglial inhibition study was performed using the anti-inflammatory agent Cyclosporin A (CsA). Importantly, long-term CsA treatment in NPC1 mice reduced reactive microgliosis, restored the survival of newly generated neurons in the OB and improved overall performance on the olfactory test. Therefore, our study highlights the possible role of microglia in the regulation of neuronal turnover in the OB and provides insight into the possible therapeutic applications of microglial inhibition in the attenuation or reversal of olfactory impairment.

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“…In support of this hypothesis, microglia are the only resident CNS cell to express CR3 (Rotshenker 2003). Microglia also secrete C1q and most complement cascade components, and activated or "reactive" microglia localize to the grey matter of cerebellum, hippocampus, and other brain regions during a narrow window of postnatal development that coincides with the peak of synapse formation and elimination (Milligan et al 1991;Dalmau et al 1998;Maslinska et al 1998;Fiske and Brunjes 2000).…”

Section: Parallels Between Complement-mediated Synapse Elimination Anmentioning

confidence: 81%

The Role of the Classical Complement Cascade in Synapse Loss During Development and Glaucoma

Rosen

Stevens

2010

Advances in Experimental Medicine and Biology

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Glaucoma is one of the leading causes of vision loss worldwide, yet the signals that initiate the progressive degeneration of optic nerve axons and the selective loss of retinal ganglion neurons (RGCs) remain elusive. Reactive gliosis, release of inflammatory cytokines, and complement upregulation all occur in the early stages of glaucoma in several disease models. Recent work has implicated the classical complement cascade in the elimination of excess synaptic connections in the developing visual system and in early synapse loss associated with glaucoma, suggesting that mechanisms of developmental synapse elimination may be aberrantly re-activated in glaucoma. This review describes current evidence in support of this "synaptic" hypothesis and places complement in the context of other well-described mechanisms of neurodegeneration occurring in the glaucomatous eye.

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Microglial activation in the developing rat olfactory bulb

Cited by 48 publications

References 60 publications

Early Activation of Microglia Triggers Long-Lasting Impairment of Adult Neurogenesis in the Olfactory Bulb

Early Activation of Microglia Triggers Long-Lasting Impairment of Adult Neurogenesis in the Olfactory Bulb

Excessive microglial activation aggravates olfactory dysfunction by impeding the survival of newborn neurons in the olfactory bulb of Niemann–Pick disease type C1 mice

The Role of the Classical Complement Cascade in Synapse Loss During Development and Glaucoma

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