Current treatments for spinal muscular atrophy have significantly improved patient prognosis, but still fall short of a full cure, particularly when administered after symptom onset. To improve future therapies, it is essential to identify the early pathological events that currently limit treatment efficacy. Here we have investigated the vulnerability and maturation of intramuscular motor axons in the SmnΔ7 mouse model of spinal muscular atrophy using a panel of cranial muscles with differing susceptibility to disease. We demonstrate that although there is intermuscular heterogeneity in neuromuscular junction pathology, they are united by a common loss of motor axons. We show that the timing of motor axon loss differs between muscles, but that motor axon loss precedes structural denervation and can occur by postnatal day 1 in highly vulnerable muscles. Electron microscopy of intramuscular axons revealed that axonal maturation and myelination are grossly normal prior to subsequent postnatal degeneration. We note that axons lack the traditional morphological correlates of axon degeneration but can be visualised using antibodies which detect degenerating neurofilaments. Treatment with SMN-upregulating therapy SMN-C8 at best preserves intramuscular axons when administered before the onset of degeneration but is unable to reverse damage or promote regeneration once axon loss has occurred. Collectively this data demonstrates that SMN-upregulating therapy can prevent motor axon loss, but the capacity is limited by the number of intramuscular axons which remain at the time of treatment onset. This work highlights the importance of developing complementary therapies which can promote motor axon regeneration to act in synergy with SMN-upregulating compounds.

The present fMRI study investigated which subregions of the visual word recognition network contribute to morphologically structured word form processing in Korean. Participants performed two separate lexical decision tasks in the scanner. In the Eojeol task, stimuli were three-syllable words composed of a disyllabic noun plus a case particle, whereas in the Noun task, stimuli were disyllabic (DSN) and trisyllabic (TSN) nouns. Behaviorally, reaction time was significantly longer in the Eojeol condition than in both DSN and TSN conditions, indicating greater processing demands for morphologically complex words, while accuracy did not differ across conditions. At the neural level, ROI analyses revealed that Eojeol processing elicited stronger activation than simple nouns in specific nodes of the visual word recognition related system, including the left inferior frontal gyrus (pars opercularis), anterior perisylvian cortex, anterior superior temporal sulcus, and anterior inferior temporal gyrus. These findings suggest that morphologically complex word recognition in Korean recruits additional resources within the visual word recognition network, highlighting the role of anterior fronto-temporal subregions in combining content and functional morphemes into unified lexical representations.

Traumatic brain injury (TBI) is a severe neurological condition associated with complex pathological cascades. Transforming growth factor-β2 (TGF-β2) is a pleiotropic cytokine that participates in multiple cellular events in the central nervous system; however, its potential protective role and molecular mechanisms in the context of TBI-induced neuronal injury have not been fully elucidated. In this study, we observed that TGF-β2 expression was markedly increased following TBI, with peak expression at day 7 post-injury. Using an in vitro LPS-induced inflammatory model, we found that exogenous TGF-β2 treatment significantly reduced the expression of pro-inflammatory factors TNF-α, IL-1β, and IL-6, as assessed by qRT-PCR, Western blot, and ELISA. Co-culture of neurons with conditioned medium from LPS-stimulated astrocytes revealed that TGF-β2 overexpression indirectly attenuated neuronal apoptosis and enhanced neuronal viability, as demonstrated by CCK-8, TUNEL staining, and molecular analyses. Mechanistic investigations suggested that the anti-inflammatory and anti-apoptotic effects of TGF-β2 may be mediated through activation of the Smad3 signaling pathway. Consistently, in vivo experiments indicated that TGF-β2 overexpression alleviated motor dysfunction and reduced neuronal apoptosis in a TBI mouse model. Collectively, these findings provide evidence for a protective role of TGF-β2 in inflammatory neuronal injury and offer insights into potential molecular targets for TBI therapeutic development.