Abstract
Primary blast injury can result in depression-like behavior in the long-term. However, the effects of the selective serotonin reuptake inhibitor (SSRI) on the depression induced by mild blast traumatic brain injury (bTBI) in the long-term remain unclear. We generated a mouse model of mild bTBI using laser-induced shock wave (LISW) and administered an SSRI to mice by oral gavage for 14 days after LISW exposure. This study aimed to investigate the mechanisms of SSRI-mediated alleviation of depression-like behavior induced by mild bTBI. Animals were divided into three groups: sham, LISW-Vehicle, and LISW-SSRI. LISW was applied to the head of anesthetized mice at 0.5 J/cm2. Twenty-eight days after the LISW, mice in the LISW-SSRI group exhibited reduced depression-like behavior, a significant increase in the number of cells co-stained for 5-bromo-2'-deoxyuridine (Brd-U) and doublecortin (DCX) in the dentate gyrus (DG) as well as increased brain-derived neurotrophic factor (BDNF) and serotonin levels in the hippocampus compared to the sham and LISW-Vehicle groups. Additionally, levels of phosphorylated cAMP response element binding protein (pCREB) in the DG were significantly decreased in the LISW-Vehicle group compared to that in the sham group. Importantly, pCREB levels were not significantly different between LISW-SSRI and sham groups suggesting that SSRI treatment may limit the downregulation of pCREB induced by mild bTBI. In conclusion, recovery from depression-like behavior after mild bTBI may be mediated by hippocampal neurogenesis induced by increased BDNF and serotonin levels as well as the inhibition of pCREB downregulation in the hippocampus.
Highlights
In recent years, the number of patients injured by bombs has increased globally [1]
We examined the effects of selective serotonin reuptake inhibitor (SSRI) administration for 2 weeks following traumatic brain injury (TBI) on behavior at 1 month post injury in a mouse model of mild blast traumatic brain injury (bTBI) using laser-induced shock wave (LISW)
Our data showed that administration of an antidepressant drug alleviated depressionlike behavior at 28 days after LISW exposure
Summary
The number of patients injured by bombs has increased globally [1]. Many soldiers suffering from mild blast traumatic brain injury (mild bTBI) from the wars in Iraq and Afghanistan experience chronic mental disorders such as depression and cognitive impairments after returning to the United States [2,3,4]. The mechanisms that lead to depression after mild bTBI remain unclear [2,3,4,5]. Novel theories regarding the mechanism of action of antidepressant drugs highlight activation of neurogenesis in the hippocampus. Stress can attenuate neurogenesis while the administration of antidepressant drugs activates neurogenesis in the hippocampal DG [7,8,9,10,11]. Chronic administration of antidepressant drugs increases pCREB, but the underlying mechanisms remain unclear [13, 14]. PCREB is thought to play an important role in hippocampal neurogenesis after TBI, but its precise mechanisms have not been fully elucidated [15,16,17,18,19]
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