Peripheral effects of central serotonin depletion in a mouse model for sub sickness behavior

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• 作者：Daniel Beis^a ; ^b ; Johan Duchene^a ; Anthony Rousselle^a ; ^b ; Maik Grohmann^a ; Fatimunnisa Qadri^a ; Michael Bader^a ; Natalia Alenina^a
• 刊名：Brain, Behavior, and Immunity
• 出版年：2013
• 出版时间：15 February, 2013
• 年：2013
• 卷：29
• 期：supp_S
• 页码：S20
• 全文大小：121 K

文摘

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 Ly6G^high/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.