Effect of sustained postnatal systemic inflammation on hippocampal volume and function in mice
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Published on: March 25, 2016
Shadi N Malaeb1, Jonathan M Davis1, Ilka M Pinz2
1Department of Pediatrics, The Floating Hospital for Children at Tufts Medical Center, Boston, Massachusetts.
Insights
Postnatal systemic inflammation in mice reduced hippocampal volume and impaired working memory. This suggests inflammation may contribute to neurodevelopmental issues in preterm infants.
Area of Science:
- Neuroscience
- Developmental Biology
- Immunology
Background:
- Premature infants face risks of lasting neurodevelopmental problems.
- Preterm birth is linked to smaller hippocampal volumes and working memory deficits.
- Perinatal inflammation is associated with preterm birth and brain abnormalities.
Purpose of the Study:
- To investigate the impact of postnatal systemic inflammation on the developing hippocampus in a mouse model.
- To determine if inflammation during early life affects hippocampal volume and function.
Main Methods:
- Mouse pups received daily lipopolysaccharide (LPS) or saline injections from postnatal day 3 to 13.
- Ex vivo MRI and microscopic brain tissue analysis were performed on day 14.
- Behavioral tests assessing memory and learning were conducted at 8-9 weeks of age.
Main Results:
- LPS-treated mice showed a 15-20% reduction in hippocampal volume compared to controls.
- Mice exposed to LPS exhibited deficits in hippocampal-dependent tasks, including novel environment recognition, object recognition memory, and fear learning.
- Impaired working memory was observed in adult mice following early-life LPS exposure.
Conclusions:
- Sustained postnatal systemic inflammation leads to reduced hippocampal volume and impaired hippocampus-dependent working memory.
- These findings support the hypothesis that systemic inflammation contributes to neurodevelopmental impairments in preterm infants.
- The study highlights a potential mechanism linking inflammation to cognitive deficits in early development.
Background:
Premature infants are at risk for persistent neurodevelopmental impairment. Children born preterm often exhibit reduced hippocampal volumes that correlate with deficits in working memory. Perinatal inflammation is associated with preterm birth and brain abnormalities. Here we examine the effects of postnatal systemic inflammation on the developing hippocampus in mice.
Methods:
Pups received daily intraperitoneal injections of lipopolysaccharide (LPS) or saline between days 3 and 13. Ex vivo magnetic resonance imaging (MRI) and microscopic analysis of brain tissue was performed on day 14. Behavioral testing was conducted at 8-9 wk of age.
Results:
MR and microscopic analysis revealed a 15-20% reduction in hippocampal volume in LPS-treated mice compared with controls. Behavioral testing revealed deficits in hippocampal-related tasks in LPS-treated animals. Adult mice exposed to LPS during the postnatal period were unable to select a novel environment when re-placed within a 1-min delay, were less able to remember a familiar object after a 1-h delay, and had impaired retention of associative fear learning after 24 h.
Conclusion:
Systemic inflammation sustained during the postnatal period contributes to reduced hippocampal volume and deficits in hippocampus-dependent working memory. These findings support the novel and emerging concept that sustained systemic inflammation contributes to neurodevelopmental impairment among preterm infants.
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