Spinal microglial morphology in a rat model of Pompe Disease
| Autor: | Kyle Deegan, Robert Martinez, Sabhya Rana, Barry Byrne, David Fuller |
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| Rok vydání: | 2023 |
| Předmět: | |
| Zdroj: | Physiology. 38 |
| ISSN: | 1548-9221 1548-9213 |
| DOI: | 10.1152/physiol.2023.38.s1.5732423 |
| Popis: | Pompe disease is a monogenic neuromuscular disorder caused by a mutation in the gene encoding the lysosomal enzyme acid alpha-glucosidase. This leads to widespread glycogen accumulation, cardiorespiratory failure, and early mortality. There is clear evidence for neurodegeneration and neuroinflammation in animal models of Pompe disease (Turner et al., Resp. Phys. Neurobio., 2016) as well as human Pompe tissues (Fuller et al., J. Neurophys., 2021). However, the appearance of microglia has not been comprehensively evaluated in Pompe disease. Here we examined this question using a rat model of Pompe disease. Mid-cervical spinal cord tissue sections of 10-13 mo old male Pompe ( Gaa null, n=3) and Sprague Dawley rats (n=3) were histologically evaluated. We focused on the mid-cervical spinal cord because this region contains the phrenic motoneurons which innervate the diaphragm muscle. Immunohistochemical processing was performed on coronal spinal cord sections using a neuronal nuclear protein (NeuN) antibody to label neurons, and an ionized calcium-binding adaptor molecule 1 (IBA-1) antibody to label microglia. Robust and reliable staining of neurons and microglia was observed in white and grey matter regions of the spinal cord section using fluorescent imaging. Putative motoneurons in the Pompe mid-cervical ventral grey matter had the “prototypical appearance” of motoneurons in lysosomal storage diseases. This included a considerably enlarged (“swollen”) soma and extensive vacuolization. Spinal cord microglia in Pompe tissues had a fundamentally different appearance as compared to Sprague-Dawley. Specifically, microglia appeared with increased density in Pompe spinal cord sections and were frequently observed to be in immediate proximity (e.g., “wrapping around”) to ventral spinal neurons which displayed a swollen and vacuolated morphology. Pompe microglia also showed a rounded appearance that is consistent with the “reactive” state known to occur during neuroinflammation. These histological data are consistent with neurodegeneration and ongoing microglia-driven phagocytosis of neurons in the mid-cervical spinal cord of adult Pompe disease rats. R01HD052682 (DDF and BJB) This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process. |
| Databáze: | OpenAIRE |
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