Sodium Monosialotetrahexosylganglioside

The prevalence of neurodegenerative diseases and mental health disorders has been increasing over the past few decades. While genetic and lifestyle factors are important to the etiology of these illnesses, the pathogenic role of environmental factors, especially toxicants such as pesticides encountered over the life span, is receiving increased attention. As an environmental factor, organophosphates pose a constant threat to human health due to their widespread use as pesticides, their deployment by rogue militaries, and their use in terrorist attacks. The standard organophosphate-antidotal regimen provides modest efficacy against lethality, although morbidity remains high, and there is little evidence that it attenuates long-term neurobehavioral sequelae. Here we show that a novel intranasally administered treatment strategy with specific gangliosides can prevent the organophosphate-related alterations in important neurotrophin pathways that are involved in cognition and depression. We found that a single exposure to the organophosphate diisopropylfluorophosphate (DFP) in mice leads to persistent decreases in the neurotrophins NGF and BDNF and their receptors, TrkA and TrkB. Moreover, 7 days of repeated intranasal administration of gangliosides GM1 or GD3 24 h after the DFP injection prevented the neurotrophin receptor alterations. As NGF and BDNF signaling are involved in cognitive function and depression symptoms, respectively, intranasal administration of GM1 or GD3 may offer a preventative strategy against organophosphate-related alterations in these brain functions. Our study thus supports the potential of a novel therapeutic strategy for neurological and psychiatric deficits associated with a class of poisons that endangers millions of people worldwide.

Influenza A virus (IAV) is a major pathogen that threatens human and animal health. In June 2022, seven golden monkeys (Rhinopithecus roxellana) developed flu-like symptoms in succession at a zoo in Jiangsu Province, China, with two succumbing to respiratory distress. Histopathological and immunostaining results supported a diagnosis of pulmonary infection with IAV, and a novel H3N2 canine/human reassortant virus, designated A/golden monkey/Jiangsu/1/2022 (Gm-1), was isolated from the lungs of deceased animals. Genomic sequencing revealed that the PB1 gene of Gm-1 exhibited > 97 % identity with human strains, while the remaining 7 segments originated from early local canine H3N2 virus (A/canine/Jiangsu/06/2010, JS06). To determine whether the human-origin PB1 segment conferred a virulence advantage to Gm-1, we reconstructed this reassortant event using reverse genetics, generating two reassortment viruses, rGm-1 (human-origin PB1) and rJS06 (canine-origin control). Mice infected with rGm-1 showed more severe lung pathology and elevated proinflammatory cytokine levels compared to rJS06, indicating that the human-origin PB1 enhanced viral virulence. Further analysis identified a unique cytotoxic motif (68I, 69 L and 70 V) in PB1-F2 protein of Gm-1, absent in JS06, which may contribute to increased pathogenicity. This is the first report confirming IAV infection in golden monkeys. Our finding highlight the importance of enhanced biosecurity surveillance for this endangered species.