SARS-CoV-2 hampers dopamine production in iPSC-derived dopaminergic neurons.

An increasing number of patients experiences prolonged symptoms, whose profile and timeline remain uncertain, a condition that has been defined as post COVID. The majority of recovered hospitalized patients manifests at least one persistent symptom even sixty days after the first clinical manifestation's onset. Particularly, in light of the COVID-19-related symptomatology, it has been hypothesized that SARS-CoV-2 might affect the dopamine pathway. However, no scientific evidence has been produced so far. To this end, human iPSC-derived dopaminergic neurons were infected with EU, Delta and Omicron SARS-CoV-2 variants. The infection with EU and Delta variants, but not with Omicron, results in a reduced intracellular content and extracellular release of dopamine. Indeed, the tyrosine hydroxylase was found to be significantly upregulated at the mRNA level, while being greatly reduced at the protein level. The major downstream synthetic enzyme DOPA-decarboxylase and the dopamine transporter were significantly downregulated both at the mRNA and protein level. Notably, in vitro SARS-CoV-2 infection was also associated with an altered MAP2 and TAU expression and with an increased presence of neuronal stress markers. These preliminary observations suggest that the dopamine metabolism and production are affected by SARS-CoV-2, partially explaining some of the neurological symptoms manifested.

Exterior Dissipation, Proportional Decay, and Integrals of Motion.

Given a dynamical system with m independent conserved quantities, we construct a multiparameter family of new systems in which these quantities evolve monotonically and proportionally, and are replaced by m-1 conserved linear combinations of themselves, with any of the original quantities as limiting cases. The modification of the dynamics employs an exterior product of gradients of the original quantities, and often evolves the system toward asymptotic linear dependence of these gradients in a nontrivial state. The process both generalizes and provides additional structure to existing techniques for selective dissipation in the literature on fluids and plasmas, nonequilibrium thermodynamics, and nonlinear controls. It may be iterated or adapted to obtain any reduction in the degree of integrability. It may enable discovery of extremal states, limit cycles, or solitons, and the construction of new integrable systems from superintegrable systems. We briefly illustrate the approach by its application to the cyclic three-body Toda lattice, driven from an aperiodic orbit toward a limit cycle.