Microglia Provide Structural Resolution to Injured Dendrites after Severe Seizures

Eyo, Ukpong B.; Mo, Mingshu; Campos-Salazar, Antony Brayan; Haruwaka, Koichiro; Wang, Lingxiao; Iv, Xenophon Speros; Sabu, Sruchika; Xu, Pingyi

doi:10.2139/ssrn.3696770

Cited by 3 publications

(4 citation statements)

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“…The release of IL-10 and other neuroprotective agents may be a necessary step in evading, or recovering from, potential TC degeneration. Similarly, astrocytes and microglia are capable of mediating and amplifying axonal and dendrite growth through mechanisms including the release of fibroblast growth factor and purinergic signaling, respectively [53][54][55][56] . The present study demonstrating a recovery effect of the observed TC dendritic retraction may be attributed to similar neuroprotective mechanisms via glial cell activity.…”

Section: Discussionmentioning

confidence: 99%

Pathological consequences of chronic olfactory inflammation on neurite morphology of olfactory bulb projection neurons

LaFever

Kawasawa

Ito

et al. 2021

Preprint

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Background : Chronic olfactory inflammation (COI) in conditions such as chronic rhinosinusitis significantly impairs the functional and anatomical components of the olfactory system. COI induced by intranasal administration of lipopolysaccharide (LPS) results in atrophy, gliosis, and pro-inflammatory cytokine production in the OB. Although chronic rhinosinusitis patients have smaller olfactory bulbs (OBs), the consequences of olfactory inflammation on OB neurons are largely unknown. Methods : In this study, we investigated the neurological consequence of COI on OB projection neurons, mitral cells (MCs) and tufted cells (TCs). To induce COI, we performed unilateral intranasal administration of LPS to mice for 4 and 10 weeks. Effects of COI on the OB were examined using RNA-sequencing approaches and immunohistochemical analyses. Results : We found that repeated LPS administration upregulated immune-related biological pathways in the OB after 4 weeks. We also determined that the length of TC lateral dendrites in the OB significantly decreased after 10 weeks of COI. The axon initial segment of TCs decreased in number and in length after 10 weeks of COI. The lateral dendrites and axon initial segments of MCs, however, were largely unaffected. In addition, dendritic arborization and axon initial segment reconstruction both took place following a 10-week recovery period. Conclusion : Our findings suggests that olfactory inflammation specifically affects TCs and their integrated circuitry, whereas MCs are potentially protected from this condition. This data demonstrates unique characteristics of the OBs ability to undergo neuroplastic changes in response to stress.

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Section: Discussionmentioning

confidence: 99%

Pathological consequences of chronic olfactory inflammation on neurite morphology of olfactory bulb projection neurons

LaFever

Kawasawa

Ito

et al. 2021

Preprint

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“…They demonstrated that the activity of neuronal mitochondria rapidly induced this microglial junction formation (Cserép et al, 2020). In distinct evidence by Eyo and co‐authors, severe seizures induce the formation of microglial process pouches targeting neuronal dendrites, which appear with a better structural resolution (Eyo et al, 2021).…”

Section: Microglia In Physiological Conditionsmentioning

confidence: 97%

“…In this regard, recent intriguing studies identified morpho‐functional communication sites between microglia and neurons. (Cserép et al, 2020; Eyo et al, 2021). Dénes and collaborators identified an interaction site between neuronal cell bodies and microglial processes in mouse and human brains.…”

Section: Microglia In Physiological Conditionsmentioning

confidence: 98%

Endocannabinoid signaling in microglia

Marinelli

Marrone

Domenico

et al. 2022

Glia

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Microglia, the innate immune cells of the central nervous system (CNS), execute their sentinel, housekeeping and defense functions through a panoply of genes, receptors and released cytokines, chemokines and neurotrophic factors. Moreover, microglia functions are closely linked to the constant communication with other cell types, among them neurons. Depending on the signaling pathway and type of stimuli involved, the outcome of microglia operation can be neuroprotective or neurodegenerative. Accordingly, microglia are increasingly becoming considered cellular targets for therapeutic intervention. Among signals controlling microglia activity, the endocannabinoid (EC) system has been shown to exert a neuroprotective role in many neurological diseases. Like neurons, microglia express functional EC receptors and can produce and degrade ECs. Interestingly, boosting EC signaling leads to an antiinflammatory and neuroprotective microglia phenotype. Nonetheless, little evidence is available on the microglia-mediated therapeutic effects of EC compounds. This review focuses on the EC signals acting on the CNS microglia in physiological and pathological conditions, namely on the CB1R, CB2R and TRPV1-mediated regulation of microglia properties. It also provides new evidence, which strengthens the understanding of mechanisms underlying the control of microglia functions by ECs. Given the broad expression of the EC system in glial and neuronal cells, the resulting picture is the need for in vivo studies in transgenic mouse models to dissect the contribution of EC microglia signaling in the neuroprotective effects of EC-derived compounds.

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“…These seizures triggered specific remodelling of microglial processes which establish long‐lasting contacts with injured neuronal dendrites. These contacts (named ‘pouches’) assisted recovery of seizure‐affected dendrites (Eyo et al ., 2021). It remains unclear whether these genetic signatures of microglia translate into a recovery morphotype, or whether transcriptional changes reflect a subtler transformation associated with increased neuroprotection.…”

Section: Microglial Morphotypes In Pathologymentioning

confidence: 99%

Plasticity of microglia

et al. 2021

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Microglial cells are the scions of foetal macrophages which invade the neural tube early during embryogenesis. The nervous tissue environment instigates the phenotypic metamorphosis of foetal macrophages into idiosyncratic surveilling microglia, which are generally characterised by a small cell body and highly ramified motile processes that constantly scan the nervous tissue for signs of changes in homeostasis and allow microglia to perform crucial homeostatic functions. The surveilling microglial phenotype is evolutionarily conserved from early invertebrates to humans. Despite this evolutionary conservation, microglia show substantial heterogeneity in their gene and protein expression, as well as morphological appearance. These differences are age, region and context specific and reflect a high degree of plasticity underlying the life‐long adaptation of microglia, supporting the exceptional adaptive capacity of the central nervous system. Microgliocytes are essential elements of cellular network formation and refinement in the developing nervous tissue. Several distinct patrolling modes of microglial processes contribute to the formation, modification, and pruning of synapses; to the support and protection of neurones through microglial–somatic junctions; and to the control of neuronal and axonal excitability by specific microglia–axonal contacts. In pathology, microglia undergo proliferation and reactive remodelling known as microgliosis, which is context dependent, yet represents an evolutionarily conserved defence response. Microgliosis results in the emergence of multiple disease and context‐specific reactive states; in addition, neuropathology is associated with the appearance of specific protective or recovery microglial forms. In summary, the plasticity of microglia supports the development and functional activity of healthy nervous tissue and provides highly sophisticated defences against disease.

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Microglia Provide Structural Resolution to Injured Dendrites after Severe Seizures

Cited by 3 publications

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Pathological consequences of chronic olfactory inflammation on neurite morphology of olfactory bulb projection neurons

Pathological consequences of chronic olfactory inflammation on neurite morphology of olfactory bulb projection neurons

Endocannabinoid signaling in microglia

Plasticity of microglia

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