title: Differential Expression of FosB Proteins and Potential Target Genes in Select Brain Regions of Addiction and Depression Patients.
abstract: Chronic exposure to stress or drugs of abuse has been linked to altered gene expression throughout the body, and changes in gene expression in discrete brain regions are thought to underlie many psychiatric diseases, including major depressive disorder and drug addiction. Preclinical models of these disorders have provided evidence for mechanisms of this altered gene expression, including transcription factors, but evidence supporting a role for these factors in human patients has been slow to emerge. The transcription factor ΔFosB is induced in the prefrontal cortex (PFC) and hippocampus (HPC) of rodents in response to stress or cocaine, and its expression in these regions is thought to regulate their "top down" control of reward circuitry, including the nucleus accumbens (NAc). Here, we use biochemistry to examine the expression of the FosB family of transcription factors and their potential gene targets in PFC and HPC postmortem samples from depressed patients and cocaine addicts. We demonstrate that ΔFosB and other FosB isoforms are downregulated in the HPC but not the PFC in the brains of both depressed and addicted individuals. Further, we show that potential ΔFosB transcriptional targets, including GluA2, are also downregulated in the HPC but not PFC of cocaine addicts. Thus, we provide the first evidence of FosB gene expression in human HPC and PFC in these psychiatric disorders, and in light of recent findings demonstrating the critical role of HPC ΔFosB in rodent models of learning and memory, these data suggest that reduced ΔFosB in HPC could potentially underlie cognitive deficits accompanying chronic cocaine abuse or depression.
authors: Genetics Program, Michigan State University, East Lansing, Michigan, United States of America.
authors: Paula A
authors: PA
authors: Gajewski
authors: McGill Group for Suicide Studies, Douglas Mental Health University Institute and McGill University, Montréal, Québec, Canada.
authors: Gustavo
authors: G
authors: Turecki
authors: Genetics Program, Michigan State University, East Lansing, Michigan, United States of America.|Department of Physiology, Michigan State University, East Lansing, Michigan, United States of America.
authors: Alfred J
authors: AJ
authors: Robison
mesh_terms: D000328:Adult; D000818:Animals; D000928:Antidepressive Agents / Q000627:therapeutic use; D016022:Case-Control Studies; D019970:Cocaine-Related Disorders / Q000235:genetics* / Q000473:pathology; D003863:Depression / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D005260:Female; D005786:Gene Expression Regulation; D006624:Hippocampus / Q000502:physiology* / Q000503:physiopathology; D006801:Humans; D008297:Male; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D017397:Prefrontal Cortex / Q000502:physiology* / Q000503:physiopathology; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics* / Q000378:metabolism; D018091:Receptors, AMPA / Q000235:genetics
chemical_list: D000928:Antidepressive Agents; C064269:FOSB protein, human; C483819:Fosb protein, mouse; D016760:Proto-Oncogene Proteins c-fos; D018091:Receptors, AMPA; C104722:glutamate receptor ionotropic, AMPA 2