Biology subjects

Chen, C.-R.

Publications and source records attributed to Chen, C.-R..

3 recordsLinked to original sources

bioRxiv2023

Hypothalamic CRH Neurons Modulate Sevoflurane Anesthesia and The Post-anesthesia Stress Responses

General anesthesia is an indispensable procedure necessary for safely and compassionately administering a significant number of surgical procedures and invasive diagnostic tests. However, the undesired stress response associated with general anesthesia (GA) causes delayed recovery and even increased morbidity in the clinic. Here, a core hypothalamic ensemble, corticotropin-releasing hormone neurons in the paraventricular nucleus of the hypothalamus (PVHCRH neurons), is discovered to play a role in regulating sevoflurane GA. Chemogenetic activation of these neurons delay the induction of and accelerated emergence from sevoflurane GA, whereas chemogenetic inhibition of PVHCRH neurons accelerates induction and delays awakening. Moreover, optogenetic stimulation of PVHCRH neurons induce rapid cortical activation during both the steady and deep sevoflurane GA state with burst-suppression oscillations. Interestingly, chemogenetic inhibition of PVHCRH neurons relieve the sevoflurane GA-elicited stress response (e.g., excessive self-grooming and elevated corticosterone level). These findings identify PVHCRH neurons modulate states of anesthesia in sevoflurane GA, being a part of anesthesia regulatory network of sevoflurane. Impact statementDiscovery of critical brain nodes regulating sevoflurane general anesthesia and the post-anesthesia stress responses.

neuroscience↗

bioRxiv2021

Dysfunctions of the paraventricular hypothalamic nucleus induce hypersomnia in human and mice

Hypersomnolence disorder (HD) is characterized by excessive sleep, which is a common sequela following stroke, infections or tumorigenesis. HD was traditionally thought to be associated with lesions of wake-promoting nuclei. However, lesion of a single, even two or more wake-promoting nucleuses simultaneously did not exert serious HD. The specific nucleus and neural circuitry for HD remain unknown. Here, we observed that three patients with lesions around the paraventricular nucleus of the hypothalamus (PVH) showed hypersomnolence lasting more than 20 h per day and their excessive sleep decreased with the recovery of the PVH area. Therefore, we hypothesized that the PVH might play an essential role in the occurrence of HD. Using multichannel electrophysiological recording and fiber photometry, we found that PVHvglut2 neurons were preferentially active during wakefulness. Chemogenetic activation of PVHvglut2 neurons potently induced 9-h wakefulness, and PVHCRH, PVHPDYN and PVHOT neuronal activation also exerted wakefulness. Most importantly, ablation of PVHvglut2 neurons drastically induced hypersomnia-like behaviors (30.6% reduction in wakefulness). These results indicate that dysfunctions of the PVH is crucial for physiological arousal and pathogenesis underlying HD.

neuroscience↗

bioRxiv2018

Nifedipine Modulated Renal Lipogenesis via AMPK-SREBP Transcriptional Pathways

Lipid accumulation in renal cells has been implicated in the pathogenesis of obesity-related kidney disease, and lipotoxicity occurring in the kidney can be a surrogate marker for renal failure or renal fibrosis. Nifedipine-induced renal lipotoxicity has never been cited, although a few studies have shown that nifedipine inhibits lipogenesis via activation of the LKB1-AMPK pathway. Therefore, we utilized NRK52E cell models to examine this further. We pre-treated cells with varying concentrations of nifedipine (7.5, 15, or 30 M) for 24 or 48 h prior to examining the activity of lipogenesis enzymes and lipotoxicity.\n\nNifedipine was found to activate acetyl CoA synthetase, acetyl CoA carboxylase, long chain fatty acyl CoA elongase, ATP-citrate lyase, and HMG CoA reductase, suggesting elevated production of cholesterol, triacylglycerides, and phospholipids. Nifedipine exposure induced a vast accumulation of cytosolic free fatty acids (FFA) and stimulated the production of reactive oxygen species, upregulated CD36 and KIM-1 (kidney injury molecule-1) expression, inhibited p-AMPK activity, and triggered the transcription of SREBP-1/2 and lipin-1, underscoring the potential of nifedipine to induce lipotoxicity with renal damage.\n\nIn the present study, we elucidated the mechanism of action of nifedipine that leads to renal lipotoxicity via the AMPK-SREBP-1/2 pathway. To our knowledge, this is the first report demonstrating nifedipine-induced lipid accumulation in the kidney.

biochemistry↗