| 8:34p |
Influenza A Virus infection is associated with TDP-43 pathology and neuronal damage in the brain
Viral pandemics such as COVID-19 have demonstrated long-term neurological consequences, including memory impairment and depression, emphasizing the importance of understanding virus-brain interactions [1]. Similar concerns have been raised for Influenza A virus (IAV), which has been implicated in neurodegenerative disorders [2, 3]. In this study, we investigated the neuropathological effects of highly pathogenic avian influenza (HPAI) H5N1 and H5N8 strains in a mouse model. Although viral RNA was detected in the brain post-infection, no viral proteins were found, suggesting limited or transient brain replication. Despite this, infected brains showed significant neuronal damage, including axonal loss and nuclear condensation, as evidenced by immunofluorescence and Nissl staining. We also observed pathological changes in TDP-43, including conformational alterations and increased phosphorylation, which required antigen retrieval for detection--features reminiscent of those found in frontotemporal dementia and amyotrophic lateral sclerosis [4, 5]. Transcriptomic analysis further revealed strain-specific host responses, including activation of interferon-related genes and downregulation of microtubule-associated pathways. These findings suggest that IAV infection can trigger hallmarks of neurodegeneration in the absence of persistent viral protein expression, possibly through host-driven mechanisms. Our results underscore the need for further investigation into virus-induced molecular pathways contributing to neurodegenerative disease. |
| 9:47p |
Neural adolescent pragmatic development mirrors pragmatic differences in adulthood: an fMRI-study
Pragmatic development is still ongoing during adolescence. However, the developmental trajectory during the adolescent years is understudied and the underlying neural correlates of pragmatic development are unknown. In this study, we used an established fMRI paradigm contrasting indirect and direct speech act processing in a newly acquired adolescent sample (n = 51) and a previously collected adult sample (n = 57). The adolescent sample was split into two groups: Young (ages 13-15) and Mid (ages 16-18); and the adult sample (Old, ages 18-36) into two groups based on pragmatic skill level, established in separate behavioral tests. We observed increased activity with age in the posterior medial prefrontal cortex, and a combination of age-related differences and individual differences in adults in the left posterior intraparietal sulcus (IPS) and the posterior cingulate cortex. These clusters were all located outside of the classical perisylvian language areas ("the language network"). The posterior cingulate cortex cluster overlapped with core nodes of the default mode network. We interpret the IPS finding in terms of its overlap with two relevant networks (one of them is the "multiple demand" network related to cognitive control). The results indicate that young adolescents and adults with low pragmatic skill may be over-interpreting direct speech acts as potentially indirect. The similarity between these two groups across results in turn indicate that a delayed adolescent development may lead to persistent difficulties in adulthood. We have shown that aspects of pragmatic development depend on cognitive abilities other than language and Theory of Mind. By studying adolescence, a presumably uniquely human extended developmental period, we provide a rare empirical angle on the question of which aspects of brain and cultural evolution contributed to the human communicative faculty. |