Gene expression profiling reveals complex changes in the olfactory bulbectomy model of depression after chronic
Kou Takahashi1, Akiyoshi Saitoh, Misa Yamada
1Department of Psychogeriatrics, National Institute of Mental Health, National Center of Neurology and Psychiatry, Tokyo, Japan.
Abstract:
We investigated the effects of antidepressants on the gene expression profile and behavior of olfactory-bulbectomized (OBX) rats. Removal of the main olfactory bulbs in rats alters neuronal function in brain areas involved in emotional regulation, resulting in maladaptive behavioral patterns similar to the symptoms of patients with depression. Previously, we found that OBX-induced behavioral and neuronal abnormalities were completely rescued by chronic treatment with SNC80, an opioid delta agonist, as well as with classical monoaminergic antidepressants. Thus, to determine the basis for this effect, we analyzed gene expression in OBX rat frontal cortex using a GeneChip rat Genome oligonucleotide array after imipramine or SNC80 treatment. We found that imipramine and SNC80 induced the following systematic changes in OBX rats: zinc ion binding; hydrolase activity, acting on acid anhydrides, in phosphorus-containing anhydrides; protein serine/threonine kinase activity; N-acetyltransferase activity; protein modification process; regulation of cellular process; and regulation of neurotransmitter levels. Defining the roles of candidate neuronal systems in antidepressant-induced neural changes are likely to transform the course of research on the biological basis of mood disorders.
Insights
Antidepressants like imipramine and SNC80 reversed depression-like behaviors in olfactory-bulbectomized rats. This treatment normalized gene expression changes in the frontal cortex, revealing key molecular pathways involved in mood regulation.
Area of Science:
- Neuroscience
- Molecular Biology
- Pharmacology
Background:
- Olfactory bulb removal (OBX) in rats induces depression-like behaviors and neuronal dysfunction.
- These OBX-induced abnormalities are reversed by chronic treatment with antidepressants and SNC80, an opioid delta agonist.
Purpose of the Study:
- To investigate the molecular mechanisms underlying the antidepressant effects of imipramine and SNC80 in OBX rats.
- To identify specific gene expression changes in the frontal cortex following antidepressant treatment in an animal model of depression.
Main Methods:
- Gene expression profiling of OBX rat frontal cortex using GeneChip Rat Genome oligonucleotide arrays.
- Analysis of gene expression changes after chronic treatment with imipramine or SNC80.
Main Results:
- Imipramine and SNC80 treatments induced significant changes in gene expression in OBX rats.
- Affected pathways included zinc ion binding, hydrolase activity, protein serine/threonine kinase activity, and regulation of neurotransmitter levels.
- These molecular changes correlate with the behavioral rescue observed in treated rats.
Conclusions:
- Antidepressant treatments normalize specific gene expression profiles in the frontal cortex of OBX rats.
- Identifying the roles of these affected neuronal systems is crucial for understanding the biological basis of mood disorders.
- This study provides insights into the molecular underpinnings of antidepressant action.
