| First Author | Cheung SW | Year | 2024 |
| Journal | Neuropathol Appl Neurobiol | Volume | 50 |
| Issue | 3 | Pages | e12982 |
| PubMed ID | 38742276 | Mgi Jnum | J:357783 |
| Mgi Id | MGI:7763765 | Doi | 10.1111/nan.12982 |
| Citation | Cheung SW, et al. (2024) Perineuronal nets are phagocytosed by MMP-9 expressing microglia and astrocytes in the SOD1(G93A) ALS mouse model. Neuropathol Appl Neurobiol 50(3):e12982 |
| abstractText | AIMS: Perineuronal nets (PNNs) are an extracellular matrix structure that encases excitable neurons. PNNs play a role in neuroprotection against oxidative stress. Oxidative stress within motor neurons can trigger neuronal death, which has been implicated in amyotrophic lateral sclerosis (ALS). We investigated the spatio-temporal timeline of PNN breakdown and the contributing cellular factors in the SOD1(G93A) strain, a fast-onset ALS mouse model. METHODS: This was conducted at the presymptomatic (P30), onset (P70), mid-stage (P130), and end-stage disease (P150) using immunofluorescent microscopy, as this characterisation has not been conducted in the SOD1(G93A) strain. RESULTS: We observed a significant breakdown of PNNs around alpha-motor neurons in the ventral horn of onset and mid-stage disease SOD1(G93A) mice compared with wild-type controls. This was observed with increased numbers of microglia expressing matrix metallopeptidase-9 (MMP-9), an endopeptidase that degrades PNNs. Microglia also engulfed PNN components in the SOD1(G93A) mouse. Further increases in microglia and astrocyte number, MMP-9 expression, and engulfment of PNN components by glia were observed in mid-stage SOD1(G93A) mice. This was observed with increased expression of fractalkine, a signal for microglia engulfment, within alpha-motor neurons of SOD1(G93A) mice. Following PNN breakdown, alpha-motor neurons of onset and mid-stage SOD1(G93A) mice showed increased expression of 3-nitrotyrosine, a marker for protein oxidation, which could render them vulnerable to death. CONCLUSIONS: Our observations suggest that increased numbers of MMP-9 expressing glia and their subsequent engulfment of PNNs around alpha-motor neurons render these neurons sensitive to oxidative damage and eventual death in the SOD1(G93A) ALS model mouse. |
