Mapping of hippocampal gene clusters regulated by the amygdala to nonlinkage sites for schizophrenia.
A recent study using a 'partial' rodent model of schizophrenia has employed amygdalar activation to induce reported changes in the expression of hippocampal genes associated with metabolic and signaling pathways in response to amygdalar activation. The amygdalo-hippocampal pathway plays a central role in the regulation of the stress response and emotional learning. In the current study, we have performed a chromosome mapping analysis to determine whether genes showing changes in response to environmental stress may form clusters and, if so, whether they might show a topographical association with linkage sites for schizophrenia. When the hippocampal genes showing changes in expression were topographically mapped on specific rat chromosomes, significant clustering was observed on chromosomes 1, 4 and 8, although chromosome 1 showed the largest amount of clustering. When these same rodent genes were mapped to human chromosomes, most of the genes found on chromosome 1 in rat mapped to chromosome 11 in human. The vast majority of the genes showing changes in regulation were excluded from known linkage sites for schizophrenia. Based on these findings, we postulate that environmental factors may contribute to the endophenotype for schizophrenia through the activation and/or deactivation of specific genetic clusters, ones that do not appear to be directly associated with susceptibility genes for this disorder.
Burke
R E
RE
Program in Structural and Molecular Neuroscience, McLean Hospital, Belmont 02478, and Program in Neuroscience, Harvard Medical School, Boston, MA, USA.
Walsh
J
J
Matzilevich
D
D
Benes
F M
FM
D000679:Amygdala / Q000378:metabolism*; D000818:Animals; D002874:Chromosome Mapping; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006239:Haplotypes; D006624:Hippocampus / Q000378:metabolism*; D006801:Humans; D009434:Neural Pathways / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012559:Schizophrenia / Q000235:genetics* / Q000378:metabolism*