Hetero-Integration of Silicon Nanomembranes with 2D Materials for Bioresorbable, Wireless Neurochemical System.

Although neurotransmitters are key substances closely related to evaluating degenerative brain diseases as well as regulating essential functions in the body, many research efforts have not been focused on direct observation of such biochemical messengers, rather on monitoring relatively associated physical, mechanical, and electrophysiological parameters. Here, a bioresorbable silicon-based neurochemical analyzer incorporated with 2D transition metal dichalcogenides is introduced as a completely implantable brain-integrated system that can wirelessly monitor time-dynamic behaviors of dopamine and relevant parameters in a simultaneous mode. An extensive range of examinations of molybdenum/tungsten disulfide (MoS2 /WS2 ) nanosheets and catalytic iron nanoparticles (Fe NPs) highlights the underlying mechanisms of strong chemical and target-specific responses to the neurotransmitters, along with theoretical modeling tools. Systematic characterizations demonstrate reversible, stable, and long-term operational performances of the degradable bioelectronics with excellent sensitivity and selectivity over those of non-dissolvable counterparts. A complete set of in vivo experiments with comparative analysis using carbon-fiber electrodes illustrates the capability for potential use as a clinically accessible tool to associated neurodegenerative diseases.

Aberrant Tonic Inhibition of Dopaminergic Neuronal Activity Causes Motor Symptoms in Animal Models of Parkinson's Disease.

Current pharmacological treatments for Parkinson's disease (PD) are focused on symptomatic relief, but not on disease modification, based on the strong belief that PD is caused by irreversible dopaminergic neuronal death. Thus, the concept of the presence of dormant dopaminergic neurons and its possibility as the disease-modifying therapeutic target against PD have not been explored. Here we show that optogenetic activation of substantia nigra pars compacta (SNpc) neurons alleviates parkinsonism in acute PD animal models by recovering tyrosine hydroxylase (TH) from the TH-negative dormant dopaminergic neurons, some of which still express DOPA decarboxylase (DDC). The TH loss depends on reduced dopaminergic neuronal firing under aberrant tonic inhibition, which is attributed to excessive astrocytic GABA. Blocking the astrocytic GABA synthesis recapitulates the therapeutic effect of optogenetic activation. Consistently, SNpc of postmortem PD patients shows a significant population of TH-negative/DDC-positive dormant neurons surrounded by numerous GABA-positive astrocytes. We propose that disinhibiting dormant dopaminergic neurons by blocking excessive astrocytic GABA could be an effective therapeutic strategy against PD.