Biology subjects

Molina, B.

Publications and source records attributed to Molina, B..

3 recordsLinked to original sources

bioRxiv2025

Assessment of Motoneuronal Regeneration and Wallerian Degeneration Following Axotomy in Postnatal Mice

Nerve injuries during early postnatal stages results in markedly different outcomes compared to adult injury, with significant motoneuronal death masking potential regenerative capacity. This study systematically evaluated motoneuronal survival, axonal regeneration, and Wallerian degeneration following peripheral nerve injury at distinct postnatal stages (P4, P10, and P30) in mice. Using ChAT-Cre/Ai9(RCL-tdT) and ChAT-Cre/RiboTag transgenic models, we assessed both histological and transcriptomic responses after sciatic nerve lesions. Injury at P4 induced substantial motoneuron death (1150%), whilst P10 and P30 animals showed minimal neuronal loss. However, when correcting for neuronal survival, P4 mice demonstrated the highest regenerative capacity, with surviving neurons achieving 100% axonal regeneration. Motoneuron-specific translatome analysis revealed that P30 animals activated a robust regeneration-associated gene (RAG) programme, including classical markers such as Atf3, Gap43, and Ngfr. In contrast, P4 neurons showed minimal RAG upregulation, suggesting they retain an intrinsic growth state that facilitates regeneration without requiring transcriptional reprogramming. P10 animals exhibited a transitional phenotype with impaired RAG activation and reduced regenerative capacity. Wallerian degeneration proceeded efficiently across all developmental stages, with age-specific differences in myelin clearance kinetics and macrophage recruitment. Transcriptomic analysis confirmed consistent downregulation of myelination programmes and upregulation of pro-regenerative markers following injury, regardless of age. These findings indicate that regenerative capacity is primarily determined by the intrinsic growth state of motoneurons rather than extrinsic factors. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=80 SRC="FIGDIR/small/691768v2_ufig1.gif" ALT="Figure 1"> View larger version (38K): org.highwire.dtl.DTLVardef@9079b4org.highwire.dtl.DTLVardef@12640b7org.highwire.dtl.DTLVardef@62e763org.highwire.dtl.DTLVardef@1453180_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗

bioRxiv2025

Genetic Modifiers Influencing the Acute and Long-Term Responses to Traumatic Brain Injury in Drosophila

Worldwide, traumatic brain injury (TBI) represents a major cause of mortality and long-term disability, with even mild repetitive forms of TBI (mTBI) potentially having deleterious consequences for both the acute and long-term function of the nervous system. Understanding the key cellular and molecular processes that occur following TBI exposure and potential factors that influence individual injury responses has been limited in part by the lack of comprehensive in vivo screening technique that directly compares stress sensitive and resistant genotypes involving conserved genes and functional pathways. In this report, we use a high throughput adult Drosophila trauma model system to compare the impact modest insulin signaling (IRS/chico) and autophagic defects (Atg8a/MAPLC3, Ref(2)P/SQSM1) have on traumatic injury outcomes. Using both severe and mild repetitive injury conditions the acute mortality indexes, longevity profiles, molecular and behavioral changes (locomotor, sleep) for individual fly genotypes were assessed. Compared to control cohorts (w1118/+), heterozygous chico mutants (chico1/+) demonstrated resistance, while aged flies (+2-weeks) or autophagy mutants (Atg8a1, Ref(2)Pc/e, Ref(2)Pe/+) showed heightened trauma sensitivity. Alterations that promote or impair autophagic function, longevity and stress responses were examined. Overall, this injury paradigm illustrates the effectiveness of using model systems to characterize conserved genetic factors that influence neuronal autophagy during complex trauma response. It also raises the potential for developing unique screens and therapies for patients that have experienced TBI.

genetics↗

bioRxiv2020

Cell type-specific biogenesis of novel vesicles containing viral products in human 1cytomegalovirus infection

Human cytomegalovirus (HCMV), while highly restricted for the human species, infects an unlimited array of cell types in the host. Patterns of infection are dictated by the cell type infected, but cell type-specific factors and how they impact tropism for specific cell types is poorly understood. Previous studies in primary endothelial cells showed that HCMV infection induces large multivesicular-like bodies that incorporate viral products including dense bodies and virions. Here we define the nature of these large vesicles using a recombinant virus where UL32, encoding the pp150 tegument protein, is fused in frame with green fluorescent protein (GFP, TB40/E-UL32-GFP). Cells were fixed and labeled with antibodies against subcellular compartment markers and imaged using confocal and super-resolution microscopy. In fibroblasts, UL32-GFP-positive vesicles were marked with classical markers of MVBs, including CD63 and lysobisphosphatidic acid (LBPA), both classical MVB markers, as well as the clathrin and LAMP1. Unexpectedly, UL32-GFP-positive vesicles in endothelial cells were not labeled by CD63, and LBPA was completely lost from infected cells. We defined these UL32-positive vesicles in endothelial cells using markers for the cis-Golgi (GM130), lysosome (LAMP1), and autophagy (LC3B). These findings suggest that virus-containing MVBs in fibroblasts are derived from the canonical endocytic pathway and takeover classical exosomal release pathway. Virus containing MVBs in HMVECs are derived from the early biosynthetic pathway and exploit a less characterized early Golgi-LAMP1-associated non-canonical secretory autophagy pathway. These results reveal striking cell-type specific membrane trafficking differences in host pathways that are exploited by HCMV. ImportanceHuman cytomegalovirus (HCMV) is a herpesvirus that, like all herpesvirus, that establishes a life long infection. HCMV remains a significant cause of morbidity and mortality in the immunocompromised and HCMV seropositivity is associated with increased risk vascular disease. HCMV infects many cells in the human and the biology underlying the different patterns of infection in different cell types is poorly understood. Endothelial cells are important target of infection that contribute to hematogenous spread of the virus to tissues. Here we define striking differences in the biogenesis of large vesicles that incorporate virions in fibroblasts and endothelial cells. In fibroblasts, HCMV is incorporated into canonical MVBs derived from an endocytic pathway, whereas HCMV matures through vesicles derived from the biosynthetic pathway in endothelial cells. This work defines basic biological differences between these cell types that may impact the outcome of infection.

microbiology↗