Interleukin-10/Ceftriaxone prevents E. coli-induced delays in sensorimotor task learning and spatial memory in neonatal and adult Sprague-Dawley rats.
Intrauterine infection during pregnancy is associated with early activation of the fetal immune system and poor neurodevelopmental outcomes. Immune activation can lead to alterations in sensorimotor skills, changes in learning and memory and neural plasticity. Both interleukin-10 (IL-10) and Ceftriaxone have been shown to decrease immune system activation and increase memory capacity, respectively. Using a rodent model of intrauterine infection, we examined sensorimotor development in pups, learning and memory, via the Morris water maze, and long-term potentiation in adult rats. Pregnant rats at gestational day 17 were inoculated with 1 x 10(5) colony forming units of Escherichia coli (E. coli) or saline. Animals in the treatment group received IL-10/Ceftriaxone for 3 days following E. coli administration. Intrauterine infection delayed surface righting, negative geotaxis, startle response and eye opening. Treatment with IL-10/Ceftriaxone reduced the delay in these tests. Intrauterine infection impaired performance in the probe trial in the Morris water maze (saline 25.13+/-1.01; E. coli 20.75+/-1.01; E. coli+IL-10/Ceftriaxone 20.2+/-1.62) and reduced the induction of long-term potentiation (saline 141.5+/-4.3; E. coli 128.7+/-3.9; E. coli+IL-10/Ceftriaxone 140.0+/-10). In summary, the results of this study indicate that E. coli induced intrauterine infection delays sensorimotor and learning and memory, while IL-10/Ceftriaxone rescues some of these behaviors. These delays were also accompanied by an increase in interleukin-1beta levels, which indicates immune activation. IL-10/Ceftriaxone prevents these delays as well as decreases E. coli-induced interleukin-1beta activation and may offer a window of time in which suitable treatment could be administered.
Wallace
K L
KL
Department of Obstetrics & Gynecology, University of MS Medical Center, 2500 N. State St., Jackson, MS 39216, United States. kwallace2@pharmacology.umsmed.edu
Lopez
J
J
Shaffery
J P
JP
Wells
A
A
Paul
I A
IA
Bennett
W A
WA
D000375:Aging; D000818:Animals; D000831:Animals, Newborn; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D002443:Ceftriaxone / Q000494:pharmacology*; D004927:Escherichia coli Infections / Q000188:drug therapy*; D005260:Female; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology; D016753:Interleukin-10 / Q000494:pharmacology*; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008568:Memory / Q000187:drug effects / Q000502:physiology; D009043:Motor Activity / Q000187:drug effects; D018697:Nootropic Agents / Q000494:pharmacology*; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000188:drug therapy*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013028:Space Perception / Q000187:drug effects; D016896:Treatment Outcome
D000900:Anti-Bacterial Agents; D018697:Nootropic Agents; D016753:Interleukin-10; D002443:Ceftriaxone