Open Collections

Bajaj, Hitasha

University of British Columbia

Early-life infections can have enduring consequences on brain development and function. Bacterial infections during development increase the risk for neuropsychiatric disorders later in life. However, the mechanisms underlying how illness in early life programs the brain are unknown. Bacterial infections activate the hypothalamic-pituitary-adrenal (HPA) axis and increase glucocorticoid (GC) and mineralocorticoid (MC) secretion from the adrenal glands. Exposure to lipopolysaccharide (LPS), an endotoxin found in Gram-negative bacteria, at postnatal day (PND) 5 also induces GC production in the mouse brain. It is unclear whether neonatal endotoxin exposure (“1st hit”) alters GC and MC regulation in the brain after adult endotoxin exposure (“2nd hit”). Here, male and female C57BL/6J mice were injected intraperitoneally with saline (vehicle control) or 50ug/kg LPS at PND 4 and 6 (“1st hit”). Mice were injected again with either saline or 50ug/kg LPS in adulthood (“2nd hit”) (2x2 design). The brain and blood were collected 4 hr later (n=10/sex/group). We measured 11-deoxycorticosterone, corticosterone, 11-dehydrocorticosterone, and aldosterone in the blood and microdissected brain regions. Steroid levels were quantified in the prefrontal cortex, dorsal hippocampus, ventral hippocampus, hypothalamus, and amygdala via highly specific and sensitive liquid chromatography-tandem mass spectrometry. Results show that neonatal LPS treatment alters GC and aldosterone responses to adult LPS treatment in the blood and brain. Also, males and females show different GC and aldosterone responses to adult LPS treatment. These data clarify how neonatal endotoxin exposure produces long-term alterations in brain steroid regulation in adulthood, potentially underlying behavioural impairments seen upon subsequent immune challenges later in life.

Text

2024-08-26

Attribution-NonCommercial-NoDerivatives 4.0 International

http://hdl.handle.net/2429/89028

Neuroscience

University of British Columbia

UBCV

http://creativecommons.org/licenses/by-nc-nd/4.0/