Specific astrocyte reactivity of the glia limitans superficial in the medial prefrontal cortex of experimental neuropathic pain
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| Year of publication | 2023 |
| Type | Conference abstract |
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| Description | The glia limitans superficial (GLS) astrocytes on the surface of mammalian neocortex are also referred to as subpial or marginal astrocytes. These astrocytes are washed by CSF penetrating through the pia, therefore, the GLS is considered a superficial CSF-brain barrier. We described the reactivity of rat GLS astrocytes in the medial prefrontal cortex (mPFC) in response to sham surgery, and sciatic nerve compression (SNC) which is used as a model of neuropathic pain (1). The goal of our present experiments was to explore the levels of complement component 3 (C3) and its receptor, C3aR, in the rat GLS astrocytes of mPFC 3 and 7 days after sham or SNC surgery. Further, we investigated mitogen-activated protein kinase kinase kinase 12 (MAP3K12) on day 1, 3, 7, 14 and 21 after both sham and SNC surgeries. The experiment was carried out on 33 adult male rats. All surgical procedures were performed on a left paw. Development of neuropathic pain was proved by measurement of mechanical allodynia and thermal hyperalgesia in both ipsilateral and contralateral hind paws. Immunohistochemical detection of C3, C3aR, and MAP3K12 was performed in coronal cryostat sections of mPFC, and immunofluorescence (-IF) intensities in the GLS were quantified by image analysis. Double immunostaining with GFAP antibody was used for localization of C3, C3aR, and MAP3K12 proteins in the GLS astrocytes. Intensities of C3- and C3aR-IF were significantly increased in the GLS of both sham- and SNC-operated rats and maintained for all survival periods compared to naive animals. MAP3K12-IF was increased on day 1 and peaked on day 3 after both sham and SNC surgeries, followed by decreased intensities on day 14 and 21 after both surgeries. Intensities of MAP3K12-IF in the GLS of naive control were always lower compared to all experimental groups. The results of immunodetection of C3, C3aR, and MAP3K12 proteins revealed an increased reactivity of the GLS astrocytes induced by both sham- and SNC surgeries. This indicated that both peripheral tissue and nerve injuries are able to induce a specific neuroinflammatory state of the GLS astrocytes higher than protoplasmic astrocytes in mPFC. The GLS and protoplasmic astrocytes possess distinct properties with regard to their reactivation induced by a nerve injury and the development of neuropathic pain. The GLS astrocytes undergoing neuroinflammatory profiling on the mPFC surface may facilitate the penetration of damage-associated molecular patterns from CSF into the cortex, which plays a role in the affective components of neuropathic pain. Recently published rodent studies have suggested that blocking C3/C3aR pathway a MAP3K12 after chronic constriction injury of the nerve can alleviate neuropathic pain (2, 3). These inhibitors may also modulate the GLS astrocytes, which needs further experiments. |
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