Rod-shaped microglia morphology is associated with aging in 2 human autopsy series

Bachstetter, Adam D.; Ighodaro, Eseosa T.; Hassoun, Yasmin; Aldeiri, Danah; Neltner, Janna H.; Patel, Ela; Abner, Erin L.; Nelson, Peter T.

doi:10.1016/j.neurobiolaging.2016.12.028

Cited by 63 publications

(75 citation statements)

References 27 publications

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“…We also found phagocytic rod-shaped MCs, especially along the intraretinal axons, in agreement with other works describing that rod-shaped MCs are induced by the interruption of axonal transport after insults such as axotomy or ocular hypertension [ 46 , 66 ], but also during aging [ 67 ]. Rod-shaped MCs bear the M2 phenotype, and although their function is unknown, it is hypothesized that they protect the degenerating neurons [ 29 , 67 , 68 ]. In apparent contradiction with that hypothesis, we show here that rod-shaped MCs are or have been involved in the phagocytic response.…”

Section: Discussionsupporting

confidence: 92%

Microglial dynamics after axotomy-induced retinal ganglion cell death

Nadal-Nicolás

Jiménez-López

Salinas‐Navarro

et al. 2017

J Neuroinflammation

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BackgroundMicroglial cells (MCs) are the sentries of the central nervous system. In health, they are known as surveying MCs because they examine the tissue to maintain the homeostasis. In disease, they activate and, among other functions, become phagocytic to clean the cellular debris. In this work, we have studied the behavior of rat retinal MCs in two models of unilateral complete intraorbital optic nerve axotomy which elicit a different time course of retinal ganglion cell (RGC) loss.MethodsAlbino Sprague-Dawley rats were divided into these groups: (a) intact (no surgery), (b) fluorogold (FG) tracing from the superior colliculi, and (c) FG tracing + crush or transection of the left optic nerve. The retinas were dissected from 2 days to 2 months after the lesions (n = 4–12 group/lesion and time point) and then were subjected to Brn3a and Iba1 double immunodetection. In each intact retina, the total number of Brn3a+RGCs and Iba+MCs was quantified. In each traced retina (b and c groups), FG-traced RGCs and phagocytic microglial cells (PMCs, FG+Iba+) were also quantified. Topographical distribution was assessed by neighbor maps.ResultsIn intact retinas, surveying MCs are homogenously distributed in the ganglion cell layer and the inner plexiform layer. Independently of the axotomy model, RGC death occurs in two phases, one quick and one protracted, and there is a lineal and topographical correlation between the appearance of PMCs and the loss of traced RGCs. Furthermore, the clearance of FG+RGCs by PMCs occurs 3 days after the actual loss of Brn3a expression that marks RGC death. In addition, almost 50% of MCs from the inner plexiform layer migrate to the ganglion cell layer during the quick phase of RGC loss, returning to the inner plexiform layer during the slow degeneration phase. Finally, in contrast to what happens in mice, in rats, there is no microglial phagocytosis in the contralateral uninjured retina.ConclusionsAxotomy-induced RGC death occurs earlier than RGC clearance and there is an inverse correlation between RGC loss and PMC appearance, both numerically and topographically, suggesting that phagocytosis occurs as a direct response to RGC death rather than to axonal damage.

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Section: Discussionsupporting

confidence: 92%

Microglial dynamics after axotomy-induced retinal ganglion cell death

Nadal-Nicolás

Jiménez-López

Salinas‐Navarro

et al. 2017

J Neuroinflammation

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“…A morphology similar to that which we observed in the SR 10 days after ischemia–an elongated rod-shaped nucleus and a body with short processes, is characteristic of rod-shaped microglia [ 55 , 56 , 57 , 58 ]. Rod-shaped microglia have been described in the cortex in rats with diffuse brain injury [ 56 ], in the hippocampus in older adults [ 58 ] and present in experimental models of optic nerve degeneration and in some slowly developing neurodegenerative diseases progressing to dementia [ 55 ]. Individual cells or chains from rod microglia are adjacent to neuronal processes.…”

Section: Discussionsupporting

confidence: 76%

Neurodegeneration, Myelin Loss and Glial Response in the Three-Vessel Global Ischemia Model in Rat

Ананьина

Kisel

Kudabaeva

et al. 2020

IJMS

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(1) Background: Although myelin disruption is an integral part of ischemic brain injury, it is rarely the subject of research, particularly in animal models. This study assessed for the first time, myelin and oligodendrocyte loss in a three-vessel model of global cerebral ischemia (GCI), which causes hippocampal damage. In addition, we investigated the relationships between demyelination and changes in microglia and astrocytes, as well as oligodendrogenesis in the hippocampus; (2) Methods: Adult male Wistar rats (n = 15) underwent complete interruption of cerebral blood flow for 7 min by ligation of the major arteries supplying the brain or sham-operation. At 10 and 30 days after the surgery, brain slices were stained for neurodegeneration with Fluoro-Jade C and immunohistochemically to assess myelin content (MBP+ percentage of total area), oligodendrocyte (CNP+ cells) and neuronal (NeuN+ cells) loss, neuroinflammation (Iba1+ cells), astrogliosis (GFAP+ cells) and oligodendrogenesis (NG2+ cells); (3) Results: 10 days after GCI significant myelin and oligodendrocyte loss was found only in the stratum oriens and stratum pyramidale. By the 30th day, demyelination in these hippocampal layers intensified and affected the substratum radiatum. In addition to myelin damage, activation and an increase in the number of microglia and astrocytes in the corresponding layers, a loss of the CA1 pyramidal neurons, and neurodegeneration in the neocortex and thalamus was observed. At a 10-day time point, we observed rod-shaped microglia in the substratum radiatum. Parallel with ongoing myelin loss on the 30th day after ischemia, we found significant oligodendrogenesis in demyelinated hippocampal layers; (4) Conclusions: Our study showed that GCI-simulating cardiac arrest in humans—causes not only the loss of pyramidal neurons in the CA1 field, but also the myelin loss of adjacent layers of the hippocampus.

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“…Rod‐shaped microglia form as early as 1 dpi, peak in the subacute window, and align linearly in the cortex 7 dpi (Taylor, Morganti‐Kossmann, Lifshitz, & Ziebell, ). This structure is observed in other pathological contexts, including aging and chronic viral infection (Bachstetter et al, ; Ji, Schachtschneider, Schook, Walker, & Johnson, ; Sierra et al, ; Yuan, Liang, Peng, Lin, & So, ). Thus, it may represent a conserved response to neuronal degeneration/damage.…”

Section: Introductionmentioning

confidence: 81%

Traumatic brain injury‐induced neuronal damage in the somatosensory cortex causes formation of rod‐shaped microglia that promote astrogliosis and persistent neuroinflammation

Witcher

Bray

Dziabis

et al. 2018

Glia

119

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Microglia undergo dynamic structural and transcriptional changes during the immune response to traumatic brain injury (TBI). For example, TBI causes microglia to form rod‐shaped trains in the cerebral cortex, but their contribution to inflammation and pathophysiology is unclear. The purpose of this study was to determine the origin and alignment of rod microglia and to determine the role of microglia in propagating persistent cortical inflammation. Here, diffuse TBI in mice was modeled by midline fluid percussion injury (FPI). Bone marrow chimerism and BrdU pulse‐chase experiments revealed that rod microglia derived from resident microglia with limited proliferation. Novel data also show that TBI‐induced rod microglia were proximal to axotomized neurons, spatially overlapped with dense astrogliosis, and aligned with apical pyramidal dendrites. Furthermore, rod microglia formed adjacent to hypertrophied microglia, which clustered among layer V pyramidal neurons. To better understand the contribution of microglia to cortical inflammation and injury, microglia were eliminated prior to TBI by CSF1R antagonism (PLX5622). Microglial elimination did not affect cortical neuron axotomy induced by TBI, but attenuated rod microglial formation and astrogliosis. Analysis of 262 immune genes revealed that TBI caused profound cortical inflammation acutely (8 hr) that progressed in nature and complexity by 7 dpi. For instance, gene expression related to complement, phagocytosis, toll‐like receptor signaling, and interferon response were increased 7 dpi. Critically, these acute and chronic inflammatory responses were prevented by microglial elimination. Taken together, TBI‐induced neuronal injury causes microglia to structurally associate with neurons, augment astrogliosis, and propagate diverse and persistent inflammatory/immune signaling pathways.

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Rod-shaped microglia morphology is associated with aging in 2 human autopsy series

Cited by 63 publications

References 27 publications

Microglial dynamics after axotomy-induced retinal ganglion cell death

Microglial dynamics after axotomy-induced retinal ganglion cell death

Neurodegeneration, Myelin Loss and Glial Response in the Three-Vessel Global Ischemia Model in Rat

Traumatic brain injury‐induced neuronal damage in the somatosensory cortex causes formation of rod‐shaped microglia that promote astrogliosis and persistent neuroinflammation

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