Abstract
Major Depression Disorders (MDD) are the most frequent psychiatric disorders in the Western civilization. The most popular theory highlights the depletion of serotonin (5-HT) and epinephrine in the central nervous system (CNS) as major factors contributing to the development of MDD, while other theories stress the influence of peripheral immune-activation. Here we used tryptophan hydoxylase2 (TPH2)-deficient mice, that lack the rate-limiting enzyme of 5-HT synthesis in the CNS. We established a model of mild-stimulation of the peripheral immune system by lipopolysaccharide (LPS)-treatment at a dose of 0.02 mg/kg and analyzed the physiological and behavioral responses during four hours after intraperitoneal injection of LPS or saline in Tph2-deficient (Tph2−/−) and wildtype (Tph+/+) mice. Both Tph2−/− and Tph2+/+ animals displayed typical hypoglycemia and total white blood cell depletion, but no signs of sickness behavior after LPS-administration. However, the increase in corticosterone levels was blunted in Tph2−/− mice. FACS analysis showed identical changes in T- and B-cell amounts in blood, bone marrow, and spleen of Tph2+/+ and Tph2−/− animals. Surprisingly, LPS-treated Tph2−/− mice were not able to recruit the same amount of Ly6Ghigh/CD115+/CD11b+/Gr1+ progenitor cells from bone marrow as Tph2+/+ mice and also showed no reduction of these cells in the blood. Both genotypes showed no signs of sickness or changes in exploration behavior after 4 h of injection. Evaluation of a depression-like state in the tail suspension test 2 h after the LPS administration revealed no change in wildtype animals due to treatment, but a decreased level of struggling activity in Tph2−/− mice.
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