Multichannel optrodes for photonic stimulation.

An emerging method in the field of neural stimulation is the use of photons to activate neurons. The possible advantage of optical stimulation over electrical is attributable to its spatially selective activation of small neuron populations, which is promising in generating superior spatial resolution in neural interfaces. Two principal methods are explored for cochlear prostheses: direct stimulation of nerves with infrared light and optogenetics. This paper discusses basic requirements for developing a light delivery system (LDS) for the cochlea and provides examples for building such devices. The proposed device relies on small optical sources, which are assembled in an array to be inserted into the cochlea. The mechanical properties, the biocompatibility, and the efficacy of optrodes have been tested in animal models. The force required to insert optrodes into a model of the human scala tympani was comparable to insertion forces obtained for contemporary cochlear implant electrodes. Side-emitting diodes are powerful enough to evoke auditory responses in guinea pigs. Chronic implantation of the LDS did not elevate auditory brainstem responses over 26 weeks.

Hepatic estrogen receptor α is critical for regulation of gluconeogenesis and lipid metabolism in males.

Impaired estrogens action is associated with features of the metabolic syndrome in animal models and humans. We sought to determine whether disruption of hepatic estrogens action in adult male mice could recapitulate aspects of the metabolic syndrome to understand the mechanistic basis for the phenotype. We found 17ß-estradiol (E2) inhibited hepatic gluconeogenic genes such as phosphoenolpyruvate carboxykinase 1 (Pck-1) and glucose 6-phosphatase (G6Pase) and this effect was absent in mice lacking liver estrogen receptor α (Esr1) (LERKO mice). Male LERKO mice displayed elevated hepatic gluconeogenic activity and fasting hyperglycemia. We also observed increased liver lipid deposits and triglyceride levels in male LERKO mice, resulting from increased hepatic lipogenesis as reflected by increased mRNA levels of fatty acid synthase (Fas) and acetyl-CoA carboxylase (Acc1). ChIP assay demonstrated estradiol (E2) induced ESR1 binding to Pck-1, G6Pase, Fas and Acc1 promoters. Metabolic phenotyping demonstrated both basal metabolic rate and feeding were lower for the LERKO mice as compared to Controls. Furthermore, the respiratory exchange rate was significantly lower in LERKO mice than in Controls, suggesting an increase in lipid oxidation. Our data indicate that hepatic E2/ESR1 signaling plays a key role in the maintenance of gluconeogenesis and lipid metabolism in males.