Nicole D Osier1, Lan Pham2, Bunny J Pugh3, Ava Puccio4, Dianxu Ren5, Yvette P Conley6, Sheila Alexander7, C Edward Dixon8. 1. University of Pittsburgh School of Nursing, Victoria Building, 3500 Victoria Street, Pittsburgh, PA, 15213, USA; Safar Center for Resuscitation Research, Children's Hospital of Pittsburgh of UPMC, John G. Rangos Research, Center - 6th floor, 4401 Penn Avenue, Pittsburgh, PA, 15224, USA. Electronic address: ndo8@pitt.edu. 2. University of Pittsburgh School of Nursing, Victoria Building, 3500 Victoria Street, Pittsburgh, PA, 15213, USA. Electronic address: lhp4@pitt.edu. 3. Safar Center for Resuscitation Research, Children's Hospital of Pittsburgh of UPMC, John G. Rangos Research, Center - 6th floor, 4401 Penn Avenue, Pittsburgh, PA, 15224, USA. Electronic address: bjp80@pitt.edu. 4. University of Pittsburgh School of Nursing, Victoria Building, 3500 Victoria Street, Pittsburgh, PA, 15213, USA; University of Pittsburgh Department of Neurological Surgery, Brain Trauma Research Center, UPMC Presbyterian, Suite B-400, 200 Lothrop Street, Pittsburgh, PA, 15213, USA. Electronic address: puccam@upmc.edu. 5. University of Pittsburgh School of Nursing, Victoria Building, 3500 Victoria Street, Pittsburgh, PA, 15213, USA. Electronic address: dir8@pitt.edu. 6. University of Pittsburgh School of Nursing, Victoria Building, 3500 Victoria Street, Pittsburgh, PA, 15213, USA; University of Pittsburgh Department of Human Genetics, Crabtree Hall, 130 De Soto Street, Pittsburgh, PA, 15261, USA. Electronic address: yconley@pitt.edu. 7. University of Pittsburgh School of Nursing, Victoria Building, 3500 Victoria Street, Pittsburgh, PA, 15213, USA; University of Pittsburgh School of Medicine, M240 Scaife Hall, 3550 Terrace Street, Pittsburgh, PA, 15261, USA. Electronic address: salexand@pitt.edu. 8. Safar Center for Resuscitation Research, Children's Hospital of Pittsburgh of UPMC, John G. Rangos Research, Center - 6th floor, 4401 Penn Avenue, Pittsburgh, PA, 15224, USA; University of Pittsburgh Department of Neurological Surgery, Brain Trauma Research Center, UPMC Presbyterian, Suite B-400, 200 Lothrop Street, Pittsburgh, PA, 15213, USA; VA Pittsburgh Healthcare System, 4100 Allequippa St, Pittsburgh, PA, 15261, USA. Electronic address: dixoec@upmc.edu.
Abstract
BACKGROUND: Traumatic brain injury (TBI) is a devastating and costly acquired condition that affects individuals of all ages, races, and geographies via a number of mechanisms. The effects of TBI on melatonin receptors remain unknown. PURPOSE: The purpose of this study is to explore whether endogenous changes in two melatonin receptor subtypes (MT1 and MT2) occur after experimental TBI. SAMPLE: A total of 25 adult male Sprague Dawley rats were used with 6 or 7 rats per group. METHODS: Rats were randomly assigned to receive either TBI modeled using controlled cortical impact or sham surgery and to be sacrificed at either 6- or 24-h post-operatively. Brains were harvested, dissected, and flash frozen until whole cell lysates were prepared, and the supernatant fluid aliquoted and used for western blotting. Primary antibodies were used to probe for melatonin receptors (MT1 and MT2), and beta actin, used for a loading control. ImageJ and Image Lab software were used to quantify the data which was analyzed using t-tests to compare means. RESULTS: Melatonin receptor levels were reduced in a brain region- and time point- dependent manner. Both MT1 and MT2 were reduced in the frontal cortex at 24h and in the hippocampus at both 6h and 24h. DISCUSSION: MT1 and MT2 are less abundant after injury, which may alter response to MEL therapy. Studies characterizing MT1 and MT2 after TBI are needed, including exploration of the time course and regional patterns, replication in diverse samples, and use of additional variables, especially sleep-related outcomes. CONCLUSION: TBI in rats resulted in lower levels of MT1 and MT2; replication of these findings is necessary as is evaluation of the consequences of lower receptor levels.
BACKGROUND:Traumatic brain injury (TBI) is a devastating and costly acquired condition that affects individuals of all ages, races, and geographies via a number of mechanisms. The effects of TBI on melatonin receptors remain unknown. PURPOSE: The purpose of this study is to explore whether endogenous changes in two melatonin receptor subtypes (MT1 and MT2) occur after experimental TBI. SAMPLE: A total of 25 adult male Sprague Dawley rats were used with 6 or 7 rats per group. METHODS:Rats were randomly assigned to receive either TBI modeled using controlled cortical impact or sham surgery and to be sacrificed at either 6- or 24-h post-operatively. Brains were harvested, dissected, and flash frozen until whole cell lysates were prepared, and the supernatant fluid aliquoted and used for western blotting. Primary antibodies were used to probe for melatonin receptors (MT1 and MT2), and beta actin, used for a loading control. ImageJ and Image Lab software were used to quantify the data which was analyzed using t-tests to compare means. RESULTS:Melatonin receptor levels were reduced in a brain region- and time point- dependent manner. Both MT1 and MT2 were reduced in the frontal cortex at 24h and in the hippocampus at both 6h and 24h. DISCUSSION: MT1 and MT2 are less abundant after injury, which may alter response to MEL therapy. Studies characterizing MT1 and MT2 after TBI are needed, including exploration of the time course and regional patterns, replication in diverse samples, and use of additional variables, especially sleep-related outcomes. CONCLUSION: TBI in rats resulted in lower levels of MT1 and MT2; replication of these findings is necessary as is evaluation of the consequences of lower receptor levels.
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