Transcriptome Changes in Three Brain Regions during Chronic Lithium Administration in the Rat Models of Mania and Depression

Abstract

Lithium has been the most important mood stabilizer used for the treatment of bipolar disorder and prophylaxis of manic and depressive episodes. Despite long use in clinical practice, the exact molecular mechanisms of lithium are still not well identified. Previous experimental studies produced inconsistent results due to different duration of lithium treatment and using animals without manic-like or depressive-like symptoms. Therefore, we aimed to analyze the gene expression profile in three brain regions (amygdala, frontal cortex and hippocampus) in the rat model of mania and depression during chronic lithium administration (2 and 4 weeks). Behavioral changes were verified by the forced swim test, open field test and elevated maze test. After the experiment, nucleic acid was extracted from the frontal cortex, hippocampus and amygdala. Gene expression profile was done using SurePrint G3 Rat Gene Expression whole transcriptome microarrays. Data were analyzed using Gene Spring 14.9 software. We found that chronic lithium treatment significantly influenced gene expression profile in both mania and depression models. In manic rats, chronic lithium treatment significantly influenced the expression of the genes enriched in olfactory and taste transduction pathway and long non-coding RNAs in all three brain regions. We report here for the first time that genes regulating olfactory and taste receptor pathways and long non-coding RNAs may be targeted by chronic lithium treatment in the animal model of mania.

Inflammation-Related Changes in Mood Disorders and the Immunomodulatory Role of Lithium

“…Previous preclinical studies showed that lithium reversed hyperactivity and risktaking behavior after repeated injections of amphetamine [107,108], and thus was considered a validated model of mania in rats [109][110][111]. Therefore, studies using this model of mania confirmed that lithium prevented the amphetamine-induced inhibition of ETC complexes I, II, III, and IV in the hippocampus, striatum and prefrontal cortex.…”

Electroacupuncture Reverses CUMS-Induced Depression-Like Behaviors and LTP Impairment in Hippocampus by Downregulating NR2B and CaMK II Expression

“…Neurobiological studies have confirmed that the occurrence of depression is related to multiple brain regions [34,35], mainly the prefrontal cortex (PFC), anterior cingulate cortex (ACC), thalamus, hippocampus, amygdala, and basal ganglia. Damage to the hippocampus is considered to be closely related to depression, posttraumatic stress disorder, and other mental diseases.…”