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Long range: Activating the immune system of a pregnant rat leads to behavioral and brain changes in her offspring.
Pregnant rats exposed to a virus give birth to offspring with significantly altered levels of three proteins important for brain development, according to a study published 9 June in Molecular Brain1.
Activating the immune systems of pregnant rats is known to modify brain structure and behavior in the offspring, and the effects can persist for generations. These changes are thought to be mediated by immune molecules, dubbed cytokines, that can cross the placenta and the blood-brain barrier.
In the new study, researchers injected pregnant rats with an artificial virus that activates their immune systems on days 14, 15 and 18 of pregnancy, equivalent to the second trimester in humans. Five hours after injection, the blood level of MCP1, a cytokine, is significantly higher in these rats than in those injected with saline, the study found.
At 21 days of age, the equivalent of human adolescence, the offspring of these rats have increased levels of VAMP1, a protein that plays a role in docking vesicles, bubbles that ferry chemical messengers in the brain. They also have significantly higher-than-normal levels of SOX2, which maintains stem cells and regulates the development of new neurons.
The offspring also have less GLUN1 in their brains than controls do. GLUN1 is a component of the NMDA receptor, which regulates the formation of synapses, the junctions between neurons, and helps prune neurons in early brain development.
The researchers also established that the expression of several related proteins is unaltered in these rats. For example, levels of synaptophysin and synaptotagmin, which also function in neuronal vesicles, and of GLUN2A and GLUN2B, other components of the NMDA receptor, are no different from the levels in controls.
Identifying which specific signaling molecules are altered by immune activation can help hone in on relevant pathways, the researchers say.
References:
1: Forrest C.M. et al. Mol. Brain 5, 22 (2012) PubMed
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