Journal of Physiology-London最新文献

Seeking warmth during infection is a sickness behaviour that contributes to the development of fever and is often accompanied by chills. However, the central mechanism underlying this behaviour remains unknown. We recently reported two ascending thermosensory neuronal pathways from the lateral parabrachial nucleus (LPB) of the pons that drive thermoregulatory behaviours in hot and cold environments: one pathway to the preoptic area (POA), a thermoregulatory centre, mediates heat avoidance, whereas the other to the central amygdaloid nucleus (CeA), a limbic emotion centre, mediates cold avoidance. Here we investigated the role of prostaglandin E₂ (PGE₂), a pyrogenic mediator produced during infection, in the LPB-mediated mechanism of thermoregulatory behaviour in rats. Thermal preference tests and in vivo physiological recordings revealed that PGE₂ acting on the prostaglandin EP3 receptor (EP3R) in the LPB elicits behaviour that prefers warmth to a thermoneutral temperature, thereby contributing to an increase in body core temperature. However, it does not elicit brown adipose tissue thermogenesis, an autonomic febrile response. Notably, we discovered that EP3R-expressing LPB neurons (LPB^EP3R neurons) project numerous axons to the CeA, but few to the POA. Functional neuronal tracing combined with immunostaining of Fos, a marker for neuronal activation, revealed that LPB^EP3R→CeA neurons are activated by cold ambient temperature and constitute the majority of the cold-transmitting LPB→CeA neuronal population mediating cold avoidance. These results indicate that PGE₂ action on LPB^EP3R neurons during infection elicits warmth-seeking behaviour by augmenting their cold sensory transmission to the CeA, which potentially produces the unpleasant cold sensation of chills. KEY POINTS: Seeking warmth during infection is a commonly observed sickness behaviour that contributes to the development of fever, often accompanied by chills. Prostaglandin E₂ (PGE₂), a pyrogenic mediator, elicits warmth-seeking behaviour in rats by acting on prostaglandin EP3 receptor (EP3R)-expressing neurons in the lateral parabrachial nucleus (LPB) of the pons (LPB^EP3R neurons). This PGE₂ action does not elicit thermogenesis in brown adipose tissue, an autonomic febrile response. LPB^EP3R neurons transmit cutaneous cold sensory signals to the limbic emotion centre, central amygdaloid nucleus (CeA), but scarcely innervate the thermoregulatory centre, preoptic area. These results indicate that PGE₂ acting on LPB^EP3R neurons during infection elicits warmth-seeking behaviour by augmenting cold sensory transmission to the CeA, which is a potential mechanism of chills.

The human placenta acts as a critical barrier within the body, protecting the fetus from the potentially harmful effects of xenobiotics encountered by the mother during pregnancy. Membrane transporter proteins play a central role in this protective function, yet their expression patterns and how this changes across gestation remains poorly understood. A range of in vitro models have been generated to try and understand human placental transport processes; however, uncertainties persist regarding the developmental stage and cellular composition that each model represents. This review summarises the current understanding of membrane transporter expression in the most widely used in vitro systems, including primary placental tissue, choriocarcinoma cell lines and trophoblast stem cells. It also highlights recent advances in culturing techniques. Key gaps in the knowledge are identified, and opportunities for refining experimental approaches to study xenobiotic uptake and transport across the placenta in vitro are discussed.

Intrinsic biological rhythms regulate key physiological and behavioural processes, yet the influence of sex and age on these rhythms is not fully understood. We comprehensively examined 24 h (circadian) and >24 h (infradian; 5 and 10 day) rhythms in wheel-running and ingestive behaviours in single-housed young and middle-aged male and female mice. Circadian analysis revealed that middle-aged mice, particularly females, exhibited more precise daily rhythms and shifted a greater proportion of activity and feeding to the lights-on phase than young female mice. Middle-aged animals also ran for longer durations per day, suggesting age-related changes in activity regulation. Analysis of infradian rhythms further highlighted sex- and age-specific differences. Young female mice displayed robust 5 day rhythms in wheel-running activity, which were absent in middle-aged females. In contrast, few males (young or middle-aged) showed significant 5 day rhythms. Ten-day rhythms were most prominent in male mice, while females rarely expressed this periodicity. Physiologically, middle-aged mice lost more body weight in response to single housing, with middle-aged females being most affected. Interactions among behavioural rhythms in females also showed greater complexity, which increased with age. These findings reveal distinct sex- and age-dependent patterns in circadian and infradian rhythms as well as in physiological responses to isolation. Our work highlights the need to account for sex and age in chronobiological research, with broader implications for understanding vulnerability to age-related metabolic and behavioural disorders. KEY POINTS: Physiological findings: -Middle-aged mice lost more body weight after single housing, with females most affected. Circadian findings: -Older mice show more daytime activity. -Precision in daily rhythm differs by sex and age. -Middle-aged females showed prolonged daily wheel running. Infradian findings: -Young females had robust 5 day rhythms, absent in middle-aged females. -Some males showed 5 day rhythms, but 10 day rhythms were most prominent in males. Complexity of rhythms: -Complexity of interactions among behavioural rhythms increases with age, particularly in females.