Manganese-enhanced magnetic resonance imaging reveals increased DOI-induced brain activity in a mouse model of schizophrenia

Malkova, Natalia V., et al. "Manganese-enhanced magnetic resonance imaging reveals increased DOI-induced brain activity in a mouse model of schizophrenia." Proceedings of the National Academy of Sciences (2014): 201323287. It is well known that mental illnesses, such as schizophrenia, are difficult to study in an animal model for a number or reasons, so many laboratory do their best by studying mental illness like symptoms. For this study, in order to better understand the role that the environmental risk factor maternal immune activation (MIA) plays in schizophrenia and autism, Malkova and colleges examined DOI-induced brain activity. DOI, 2,5-dimethoxy-4-iodoamphetamine, is a drug that through activation of the serotonin receptor 5-HT2AR, produces similar hallucinations as experienced in schizophrenia. Multiple methods (quantitative PCR, behavioral analysis, and MeMRI) were then used to compare differences in DOI-induced activity in control versus MIA animals. They found that there was an upregulation of drug induced head twitches, manganese accumulation in multiple areas of the brain (primary and secondary motor cortex, caudate putamen, medial group of the dorsal thalamus, and parafascicular thalamic nucleus), and expression of 5-HT2A receptor and its down stream signaling molecules in MIA mice compared to controls. What I found most interesting in this paper was the MeMRI protocol. For this experiment they first took baseline scans one week prior to the injection of manganese. Following the the I.P injection a week later they then imaged the animals at 24hrs, injected the animals with DOI, and then imaged them again 27hrs post the I.P injection. For statistical analysis, they then compared baseline levels to the 24hr image as well as the 27hr image. This may be applicable for our studies looking at differences in exercising versus sedentary brain activity of the RVLM. If we were to take baseline scans, inject manganese one week later, image the animals at 24hrs, raise and/or lower blood pressure for 8 hours and then immediately image the animals at 32hrs we may see different results then previously observed. This is one possibility I had not previously thought of. ~JI