Parkinson, R. | bioRxiv Science

bioRxiv2024

Alpha Synuclein Induced Immune Response Triggers Parkinson's Disease Like Symptoms

Increasing evidence suggests that Parkinsons disease is an autoimmune disorder, with findings of elevated peripheral blood mononuclear cell in patients, and antigenic properties of -synuclein driving both the innate and adaptive immunity. Yet, how the interaction of -synuclein and a specific immune response participates to Parkinsons disease ontogenesis has remained unanswered. Here, we reveal that autoimmune response to an -synuclein antigen underlies Parkinsons disease. We demonstrate that autoimmunity mediated by CD4+T cell activation with -synuclein -syn61-75 antigen is required to lead to immune cell infiltration and localized inflammation in the substantia nigra, triggering dopaminergic cell neurodegeneration and deficits in locomotion and gait kinematics. This study offers the first immune-induced mouse model that recapitulates all features of Parkinsons disease to study the mechanisms triggering disease onset. It provides the basis for temporally tracking symptom development, exploring preventive strategies and prodromal therapeutic interventions in Parkinsons Disease. In briefPeripheral -synuclein immunization causes Parkinsons disease-like symptoms in mice. Highlights- Both CD4+ T cells and -synuclein are essential for Parkinsons disease ontogenesis. - Peripheral injection of -syn61-75 induces significant CD4+ T cell infiltration in the mouse brain. - -syn61-75 immunization is associated with inflammation, -synuclein aggregation and dopaminergic cell loss in the substantia nigra pars compacta. - Levodopa-sensitive motor symptoms are detected 8 weeks following -syn61-75 immunization in mice. - This study offers a novel autoimmune -synuclein induced mouse model of Parkinsons disease.

neuroscience↗

bioRxiv2022

Temporal responses of bumblebee gustatory neurons encode sugar identity

The sense of taste permits the recognition of valuable nutrients and the avoidance of potential toxins. Models of gustatory coding propose that within modalities (e.g. sweet, bitter, etc.), taste ligands are not distinct stimuli. However, these models are based on data from mice or flies that have omnivorous, non-specialist diets. A specialist feeder might, however, be expected to have acuity within modality if stimulus resolution was critical to survival. Previously, we found that bumblebees have a specialized mechanism for sensing sugars whereby two gustatory receptor neurons (GRNs) within the galeal sensilla of the bees mouthparts exhibit burst of spikes. Here, we show that the temporal firing patterns of these GRNs separate sugars into four distinct groups that correlate with sugar nutritional value and palatability. We also identified a third GRN that responded to stimulation with relatively high concentrations of fructose, sucrose, and maltose. Sugars that were non-metabolizable or toxic suppressed the responses of bursting GRNs to sucrose. These abilities to encode information about sugar value are a refinement to the bumblebees sense of sweet taste that could be an adaptation that enables precise calculations of the nature and nutritional value of floral nectar.

neuroscience↗