Neonatal corticosterone mitigates autoimmune neuropsychiatric disorders associated with streptococcus in mice.
Simone MacrìChiara SpinelloJoanna WidomskaRoberta MagliozziGeert PoelmansRoberto William InvernizziRoberta CretiVeit RoessnerErika BartoliniImmaculada MargaritJeffrey GlennonGiovanni LaviolaPublished in: Scientific reports (2018)
Increased glucocorticoid concentrations have been shown to favor resilience towards autoimmune phenomena. Here, we addressed whether experimentally induced elevations in circulating glucocorticoids mitigate the abnormalities exhibited by an experimental model of Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcus (PANDAS). This is a pathogenic hypothesis linking repeated exposures to Group-A-beta-hemolytic streptococcus (GAS), autoantibodies targeting selected brain nuclei and neurobehavioral abnormalities. To persistently elevate glucocorticoid concentrations, we supplemented lactating SJL/J mice with corticosterone (CORT; 80 mg/L) in the drinking water. Starting in adolescence (postnatal day 28), developing offspring were exposed to four injections - at bi-weekly intervals - of a GAS homogenate and tested for behavioral, immunological, neurochemical and molecular alterations. GAS mice showed increased perseverative behavior, impaired sensorimotor gating, reduced reactivity to a serotonergic agonist and inflammatory infiltrates in the anterior diencephalon. Neonatal CORT persistently increased circulating glucocorticoids concentrations and counteracted these alterations. Additionally, neonatal CORT increased peripheral and CNS concentrations of the anti-inflammatory cytokine IL-9. Further, upstream regulator analysis of differentially expressed genes in the striatum showed that the regulatory effect of estradiol is inhibited in GAS-treated mice and activated in GAS-treated mice exposed to CORT. These data support the hypothesis that elevations in glucocorticoids may promote central immunomodulatory processes.
Keyphrases
- drinking water
- high fat diet induced
- room temperature
- multiple sclerosis
- transcription factor
- drug induced
- carbon dioxide
- systemic lupus erythematosus
- insulin resistance
- gene expression
- preterm infants
- adipose tissue
- escherichia coli
- pseudomonas aeruginosa
- skeletal muscle
- oxidative stress
- metabolic syndrome
- high fat diet
- wild type
- drug delivery
- air pollution
- anti inflammatory
- functional connectivity
- genome wide
- health risk
- dna methylation
- cancer therapy
- staphylococcus aureus
- electronic health record
- resting state
- heat stress
- blood brain barrier
- diabetic rats
- stress induced