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Hinton Lab

Research

The Hinton laboratory at Vanderbilt has two areas of focus.

1. Molecular mechanisms of insulin action

We focus on elucidating insulin-mediated molecular mechanisms that regulate cristae dynamics and those that regulate molecular transfer between and morphological changes of the mitochondria and the ER. These can change during pathophysiological states, such as aging, diabetes, and cardiovascular disease. The laboratory heavily utilizes serial block-face scanning electron microscopy, time-lapse confocal microscopy, proximity ligation assay, and transmission electron microscopy quantification to answer these seminal questions.

 

2. Regulation of blood pressure, baroreflex sensitivity, and stroke in the brain

The goal of our research is to identify the novel neural circuits, neurotransmitters, and intracellular molecules in the brain that are critical for blood pressure, baroreflex sensitivity, and stroke. The findings of this research will identify rational targets for development of therapeutic strategies for hypertension. Specifically, we plan to generate unique mouse models using Cre-Lox recombination with genes of interest (e.g., nuclear transcription factors, ERα/β, SRC1-3, mitochondrial gene OPA-1, and MICOS complex genes associated with cristae dynamics) manipulated in specific populations of neurons at the site of interest (i.e., medial amygdala and paraventricular nucleus). These models will be used to establish the physiological relevance of specific neural networks in the regulation of blood pressure and stroke.

Hinton, A. O., Jr, He, Y., Xia, Y., Xu, P., Yang, Y., Saito, K., Wang, C., Yan, X., Shu, G., Henderson, A., Clegg, D. J., Khan, S. A., Reynolds, C., Wu, Q., Tong, Q., & Xu, Y. (2016). Estrogen Receptor-α in the Medial Amygdala Prevents Stress-Induced Elevations in Blood Pressure in Females. Hypertension (Dallas, Tex.: 1979), 67(6), 1321–1330. https://doi.org/10.1161/HYPERTENSIONAHA.116.07175

Hinton, A. O., Jr, He, Y., Xia, Y., Xu, P., Yang, Y., Saito, K., Wang, C., Yan, X., Shu, G., Henderson, A., Clegg, D. J., Khan, S. A., Reynolds, C., Wu, Q., Tong, Q., & Xu, Y. (2016). Estrogen Receptor-α in the Medial Amygdala Prevents Stress-Induced Elevations in Blood Pressure in Females. Hypertension (Dallas, Tex. : 1979), 67(6), 1321–1330. https://doi.org/10.1161/HYPERTENSIONAHA.116.07175

Figure: Effects of selective activation of medial amygdala (MeA) SIM1 neurons. A, mCherry immunoreactivity in the MeA of SIM-Cre mice following stereotactic infection with AAV-hM3Dq-mCherry. B, Electrophysiological recording from mCherry-labeled MeA SIM1 neurons in the brain slice from a SIM1-Cre mouse stereotactically infected with AAV-hM3Dq-mCherry. Fluorescence images of mCherry-labeled hM3Dq and brightfield images. Scale bars, 10 μm. C, Representative action potential traces in mCherry-labeled MeA SIM1 neurons in response to bath application of clozapine-N-oxide (CNO; 10 μmol/L). Firing frequency (D) and resting membrane potential (E) of each neuron at baseline and after CNO treatment. Temporal changes in mean arterial pressure (F) and heart rate (G) in AAV-hM3Dq-mCherry–infected SIM1-Cre mice receiving intraperitoneal injection of saline or CNO (3 mg/kg). Data are presented as mean ± standard error of the mean (SEM); n=7 per group. *P<0.05 in two-way analysis of variance followed by post hocSidak tests.