The Effects of Different Environments in Disrupted-in-Schizophrenia-1 (DISC1) Conditional Knock-in Mice
Cytogenetics, along with linkage and association studies, implicated Disrupted-in-Schizophrenia-1 (DISC1) as a predisposing risk factor for neuropsychiatric illnesses (Chubb et al, 2008). A number of social factors, including urban birth and upbringing and the quality of the maternal-child relationship have also been shown to increase the risk of schizophrenia (Thomson et al, 2013). Abnormality of DISC1 function combined with external environmental stimuli will affect protein expression within the hippocampus and prefrontal cortex over a period of time. Following exposure to environments, animals were sacrificed at ages that have been shown to be important for CNS continued cognitive abilities (Chubb et al, 2008) and analyzed for protein expression changes. Nineteen DISC1protein sequences were chosen using bioinformatics tools from national databases for different organisms with the same protein names in order to explore DISC1's conversation across species. The N-terminal and C-terminal regions were shown to be conserved in primates, rodents, and omnivores. Phylogenetic tree analysis illustrates the evolutionary relationship of organisms. To determine protein expression changes, analysis of protein bands by silver staining disclosed several proteins from the cortex and hippocampus. For the cortex, area involved in cognitive abilities, as identified by Liquid Chromatography-Tandem Mass Spectrometry (LC/MS/MS), were alpha-enolase (Eno1) and β-Tubulin (TUBB); hippocampus (area for memory formation) protein identified was fructose-bisphosphate aldolase C (Aldoc). The forced swim test (FST) data showed a statistically significant difference (p < 0.005) between the environments and genotypes (wildtype and hDISC1 mutant). The novel object recognition test established a preference for familiar or novel objects within mice. There was also was a statistically significant difference between genders in the novel object recognition test (p < 0.05). The data also indicated a statistically significant difference between genotypes with the amount of time spent with the novel object versus the familiar object (p < 0.05). Hippocampus was the only region that showed visually detectable neuronal length differences when analyzed with TIMM staining to show morphological changes. With the interaction of proteins and hDISC1 combined with environmental stimuli, possible modifications of housing conditions and experiences will alter the incidence of being diagnosed with schizophrenia.
Christianna A Howard,
"The Effects of Different Environments in Disrupted-in-Schizophrenia-1 (DISC1) Conditional Knock-in Mice"
ETD Collection for Tennessee State University.