Central taste processing begins in the rostral nucleus of the solitary tract (rNST), a region rich in GABAergic neurons. We recently showed that chemogenetic activation of rNST GABA/GAD65 neurons dampens behavioral acceptance of palatable (sucrose and maltodextrin) and increases acceptance of unpalatable (quinine) taste stimuli (Travers et al., 2022). Here, we investigated whether suppressing activity in rNST GABA neurons likewise affects behavioral taste responsivity. Using mice in which Cre was expressed under the control of the GAD65 promoter, we made bilateral rNST injections of a Cre-dependent AAV driving expression of the inhibitory DREADD, hM4Di. Subsequently, we assessed concentration-dependent licking responses to sucrose, quinine, and quinine mixed in 300 mM sucrose. Relative to intraperitoneal injections of saline, clozapine-N-oxide injections significantly increased licking to sucrose and decreased licking to quinine, regardless of whether it was presented alone or mixed in sucrose. Neither oromotor (inter-lick intervals) nor appetitive (number of trials) variables were affected. Consistent with these behavioral effects, the neuronal activity marker, Fos, was expressed in more NST, reticular formation, and parabrachial nucleus cells following clozapine-N-oxide injections. A final experiment compared effects of chemogenetic GABA inhibition on sucrose licking in food deprived versus fed mice. Inhibiting GABA neurons enhanced sucrose licking in both homeostatic states. However, the impact was more marked under the latter state in female mice, suggesting a sex difference in the impact of satiety signals on GABA rNST neurons.

01 May 2025·Free Radical Biology and Medicine

Corrigendum to “Clozapine-N-oxide protects dopaminergic neurons against rotenone-induced neurotoxicity by preventing ferritinophagy-mediated ferroptosis” [Free Radic. Biol. Med. 212 (2024) 384–402]

Author: Zhao, Jie ; Li, Sheng ; Wang, Qingshan ; Hong, Jau-Shyong ; Wang, Yan ; Hou, Liyan ; Sun, Qingquan

02 Apr 2025·Nano Letters

Deep Learning-Assisted SERS for Therapeutic Drug Monitoring of Clozapine in Serum on Plasmonic Metasurfaces

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Author: Zheng, Peng ; Barman, Ishan ; Semancik, Steve

Clozapine is widely regarded as one of the most effective therapeutics for treatment-resistant schizophrenia. Despite its proven efficacy, the therapeutic use of clozapine is complicated by its narrow therapeutic index, which necessitates rapid and precise therapeutic drug monitoring (TDM) to optimize patient outcomes and minimize adverse effects. However, conventional techniques, such as high-performance liquid chromatography, are limited by their high costs, complex instrumentation, and long turnaround times. Herein, we propose a novel approach that integrates artificial neural networks (ANNs) with surface-enhanced Raman spectroscopy (SERS) on a plasmonic metasurface for rapid TDM of clozapine and its two primary metabolites, norclozapine and clozapine-N-oxide, in human serum. The ANN-SERS strategy enables accurate classification and robust concentration prediction of the three analytes. We envision that the integrated ANN-SERS framework could deliver a scalable biomedical diagnostic and therapeutic tool for studying a wide variety of chemical and biological molecules in clinical settings.

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