The neuropeptide VGF (non-acronymic) is induced by brain-derived neurotrophic factor and promotes hippocampal neurogenesis, as well as synaptic activity. However, morphological changes induced by VGF have not been elucidated. Developing hippocampal neurons were exposed to VGF through bath application or virus-mediated expression in vitro. VGF-derived peptide, TLQP-62, enhanced dendritic branching, and outgrowth. Furthermore, VGF increased dendritic spine density and the proportion of immature spines. Spine formation was associated with increased synaptic protein expression and co-localization of pre- and postsynaptic markers. Three non-synonymous single nucleotide polymorphisms (SNPs) were selected in human VGF gene. Transfection of N2a cells with plasmids containing these SNPs revealed no relative change in protein expression levels and normal protein size, except for a truncated protein from the premature stop codon, E525X. All three SNPs resulted in a lower proportion of N2a cells bearing neurites relative to wild-type VGF. Furthermore, all three mutations reduced the total length of dendrites in developing hippocampal neurons. Taken together, our results suggest VGF enhances dendritic maturation and that these effects can be altered by common mutations in the VGF gene. The findings may have implications for people suffering from psychiatric disease or other conditions who may have altered VGF levels.

BACKGROUND:The U.S. Food and Drug Administration has to date granted approval or emergency use authorization to three vaccines against severe acute respiratory syndrome coronavirus 2 and coronavirus disease 2019. In clinical trials and real-use observational studies, the Pfizer-BioNTech BNT162b2 messenger RNA coronavirus disease 2019 vaccine, as well as the Moderna mRNA-1273 messenger RNA coronavirus disease 2019 vaccine, have demonstrated high efficacy and few adverse events.

Abstract:Necrotizing Autoimmune Myopathy (NAM) associated with 3-hydroxy-3-methylglutarylcoenzyme A Reductase (HMGCR) antibodies has been described in statin-induced and statin-naive patients. Proximal muscle weakness is the presenting symptom in HMGCR NAM. Creatine Kinase (CK) levels can exceed 10x normal values. Statininduced cases involve two thirds of HMGCR NAM patients and are more likely to respond to immunosuppressive therapy. Muscle biopsy confirms the diagnosis. We report a case with progressive oropharyngeal dysphagia as the presenting complaint with delayed response to treatment. To our knowledge, there has been only one previously reported case of statin-exposed HMGCR NAM with a similar presentation.