Brain injury results in lower levels of melatonin receptors subtypes MT1 and MT2.

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.

Variation in PPP3CC Genotype Is Associated with Long-Term Recovery after Severe Brain Injury.

After experimental traumatic brain injury (TBI), calcineurin is upregulated; blocking calcineurin is associated with improved outcomes. In humans, variation in the calcineurin A-gamma gene (PPP3CC) has been associated with neuropsychiatric disorders, though any role in TBI recovery remains unknown. This study examines associations between PPP3CC genotype and mortality, as well as gross functional status assessed at admission using the Glasgow Coma Scale (GCS) and at 3, 6, and 12 months after severe TBI using the Glasgow Outcome Score (GOS). The following tagging single nucleotide polymorphisms (tSNPs) in PPP3CC were genotyped: rs2443504, rs2461491, rs2469749, and rs10108011. The rs2443504 AA genotype was univariately associated with GCS (p = 0.022), GOS at 3, 6, and 12 months (p = 0.002, p = 0.034, and p = 0.004, respectively), and mortality (p = 0.007). In multivariate analysis controlling for age, sex, and GCS, the AA genotype of rs2443504 was associated with GOS at 3 (p = 0.02), and 12 months (p = 0.01), with a trend toward significance at 6 months (p = 0.05); the AA genotype also was associated with mortality in the multivariate model (p = 0.04). Further work is warranted to better understand the role of calcineurin, as well as the genes encoding it and their relevance to outcomes after brain injury.