Antipsychotics differentially regulate insulin, energy sensing, and inflammation pathways in hypothalamic rat neurons

Psychoneuroendocrinology
Chantel KowalchukMargaret K Hahn

Abstract

Second generation antipsychotic (AP)s remain the gold-standard treatment for schizophrenia and are widely used on- and off-label for other psychiatric illnesses. However, these agents cause serious metabolic side-effects. The hypothalamus is the primary brain region responsible for whole body energy regulation, and disruptions in energy sensing (e.g. insulin signaling) and inflammation in this brain region have been implicated in the development of insulin resistance and obesity. To elucidate mechanisms by which APs may be causing metabolic dysregulation, we explored whether these agents can directly impact energy sensing and inflammation in hypothalamic neurons. The rat hypothalamic neuronal cell line, rHypoE-19, was treated with olanzapine (0.25-100 uM), clozapine (2.5-100 uM) or aripiprazole (5-20 uM). Western blots measured the energy sensing protein AMPK, components of the insulin signaling pathway (AKT, GSK3β), and components of the MAPK pathway (ERK1/2, JNK, p38). Quantitative real-time PCR was performed to determine changes in the mRNA expression of interleukin (IL)-6, IL-10 and brain derived neurotrophic factor (BDNF). Olanzapine (100 uM) and clozapine (100, 20 uM) significantly increased pERK1/2 and pJNK protein expre...Continue Reading

Citations

May 7, 2020·Frontiers in Endocrinology·Samantha Alvarez-HerreraLenin Pavón
Mar 11, 2020·Frontiers in Psychiatry·David R Goldsmith, Mark Hyman Rapaport
Aug 30, 2020·Basic & Clinical Pharmacology & Toxicology·Ekramy ElmorsySoad Mosad
Nov 24, 2020·Journal of Neuroendocrinology·Denise D Belsham, Prasad S Dalvi
Mar 17, 2021·International Clinical Psychopharmacology·Masaru Nakamura, Takahiko Nagamine
Aug 21, 2021·Journal of Trace Elements in Medicine and Biology : Organ of the Society for Minerals and Trace Elements (GMS)·İlkay Keleş AltunÖzcan Erel

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