Change to in utero brain development caused by a certain molecule could increase a person’s risk of developing schizophrenia and a variety of other psychiatric problems, according to a team of scientists at the Scripps Research Institute.
The researchers, led by Professor Jerold Chun, focused on a lipid molecule called lysophosphatidic acid (LPA), which is produced during brain hemorrhages. Scientists know that in utero brain hemorrhaging, termed fetal cerebral hemorrhage, is a strong risk factor for schizophrenia later in life. Moreover, previous research has linked higher LPA levels to structural changes in the fetal brain, as well as a fluid accumulation called hydrocephalus that distorts brain architecture.
The study attempted to recreate the effects of fetal cerebral hemorrhage in mice and to measure its impact on the development of schizophrenia-like symptoms. Three groups of fetal mice received three different injections: saline solution, pure LPA, or blood serum (which naturally contains LPA).
Researchers then tested mice for schizophrenia-like symptoms ten weeks after birth. In female mice which had received the LPA or blood serum injection, the scientist observed hyperactivity, anxiety and an elevated count of dopamine-creating neurons. These symptoms are all associated with schizophrenia.
Female mice in the two LPA-injection groups also reacted to the “prepulse inhibition test” in a way characteristic of schizophrenia. The test involves playing a sudden soft tone before a sudden loud tone; the loud tone is less likely to startle healthy mice and humans if preceded by a soft tone. However, mice with schizophrenia show the same level of agitation with and without a preceding soft tone; the two LPA-mice groups exhibited this phenomenon.
The Scripps researchers also found schizophrenia-like alterations in the cells that regulate neurotransmitter activity; they also matched gene expressions in the LPA mice to biomarkers associated with schizophrenia in humans.
When they introduce a molecule that suppressed LPA in the brain, the scientists were able to prevent schizophrenia-like symptoms in the mice.
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