Gettings, S. M. | bioRxiv Science

bioRxiv2024

ZFHX3 plays a role in pain and cautious-like behaviours in mice

A missense mutation in zinc finger homeobox-3 (ZFHX3) gene is known to alter circadian rhythms and metabolism. ZFHX3 is highly expressed in the central nucleus of amygdala and so we investigated whether female and male Zfhx3Sci-/+ mice have impaired pain, fear, anxiety-like, and cautious-like behaviours as these behaviours which are associated with the central nucleus of the amygdala. Using mechanical and thermal sensitivity test, the fear conditioning test and the light-dark box test, we found that female Zfhx3Sci-/+ mice have hypoalgesia to mechanical stimulus while hyperalgesia to heat stimulus. Additionally, both female and male Zfhx3Sci-/+ display reduction of cautious-like behaviour. While neither female and male Zfhx3Sci-/+ mice showed a difference in fear conditioning or anxiety-like behaviour, we have demonstrated for the first time that ZFHX3 is involved in pain and cautious behaviours. HighlightsO_LIFemale and male Zfhx3Sci/+ mice displayed less cautious-like behaviour C_LIO_LIZfhx3Sci/+ female mice had hypoalgesia to noxious mechanical stimulus C_LIO_LIZfhx3Sci/+ female mice had hyperalgesia to noxious heat stimulus C_LI

animal behavior and cognition↗

bioRxiv2023

Polyethylene terephthalate (PET) micro- and nanoplastic particles affect the mitochondrial efficiency of human brain vascular pericytes without inducing oxidative stress

The objective of this investigation was to evaluate the influence of micro- and nanoplastic particles composed of polyethylene terephthalate (PET), a significant contributor to plastic pollution, on human brain vascular pericytes. Specifically, we delved into their impact on mitochondrial functionality, oxidative stress, and the expression of genes associated with oxidative stress and ferroptosis. Our findings demonstrate that the exposure of a monoculture of human brain vascular pericytes to PET particles in vitro at a concentration of 50 ppm for a duration of 6 days did not elicit oxidative stress. Notably, we observed an augmentation in various aspects of mitochondrial respiration, including extracellular acidification, proton pump leakage, maximal respiration, spare respiratory capacity, and ATP production in pericytes subjected to PET particles. Furthermore, there were no statistically significant alterations in mitochondrial DNA copy number, or the expression of genes linked to oxidative stress and ferroptosis. These outcomes suggest that, at a concentration of 50 parts per million (ppm) and for 6 days exposure, PET particles do not induce oxidative stress in human brain vascular pericytes. Instead, they seem to incite a potential mitochondrial hormesis, also named mitohormesis, response, which seemingly enhances mitochondrial function. Further investigations are warranted to explore the stages of mitohormesis and the potential consequences of plastics on the integrity of the blood-brain barrier and intercellular interactions. This research contributes to our comprehension of the potential repercussions of nanoplastic pollution on human health and underscores the imperative need for ongoing examinations into the exposure to plastic particles. Graphical Abstract (created with BioRender.com) O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=140 SRC="FIGDIR/small/563735v1_ufig1.gif" ALT="Figure 1"> View larger version (59K): org.highwire.dtl.DTLVardef@2ea981org.highwire.dtl.DTLVardef@17a7619org.highwire.dtl.DTLVardef@df661eorg.highwire.dtl.DTLVardef@a9518f_HPS_FORMAT_FIGEXP M_FIG C_FIG HighlightO_LIFabrication of polyethylene terephthalate (PET) micro- and nanoplastics C_LIO_LIPET particles increase pericytes mitochondrial respiration functions C_LIO_LIPET particles increase pericytes extracellular acidification C_LIO_LIOxidative stress was not observed in pericytes subjected to PET particles C_LI

neuroscience↗