PMID- 36291274 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20221030 IS - 2076-3425 (Print) IS - 2076-3425 (Electronic) IS - 2076-3425 (Linking) VI - 12 IP - 10 DP - 2022 Oct 4 TI - Blast Exposure Dysregulates Nighttime Melatonin Synthesis and Signaling in the Pineal Gland: A Potential Mechanism of Blast-Induced Sleep Disruptions. LID - 10.3390/brainsci12101340 [doi] LID - 1340 AB - Blast-induced traumatic brain injury (bTBI) frequently results in sleep-wake disturbances. However, limited studies have investigated the molecular signaling mechanisms underlying these sleep disturbances, and potentially efficacious therapies are lacking. We investigated the levels of melatonin and genes involved in melatonin synthesis pathway in the pineal glands of Sprague Dawley rats exposed to single and tightly coupled repeated blasts during the night and daytime. Rats were exposed to single and tightly coupled repeated blasts using an advanced blast simulator. The plasma, cerebrospinal fluid (CSF), and pineal gland were collected at 6 h, 24 h, or 1 month postblast at two different time points: one during the day (1000 h) and one at night (2200 h). Differential expressions of genes involved in pineal melatonin synthesis were quantified using quantitative real-time polymerase chain reaction (qRT-PCR). Plasma and CSF melatonin levels were assessed using a commercial melatonin ELISA kit. The plasma and CSF melatonin levels showed statistically significant decreases at 6 h and 24 h in the blast-exposed rats euthanized in the night (in dim light), with no significant alterations noted in rats euthanized in the morning (daylight) at all three-time points. Blast-exposed rats showed statistically significant decreases in Tph1, Aanat, Asmt, and Mtnr1b mRNA levels, along with increased Tph2 mRNA, in the pineal gland samples collected at night at 6 h and 24 h. No significant changes in the mRNA levels of these genes were noted at 1 month. These findings imply that the melatonin circadian rhythm is disrupted following blast exposure, which may be a factor in the sleep disturbances that blast victims frequently experience. FAU - Govindarajulu, Manoj AU - Govindarajulu M AD - Blast-Induced Neurotrauma Branch, Center for Military Psychiatry and Neurosciences, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA. FAU - Patel, Mital Y AU - Patel MY AD - Blast-Induced Neurotrauma Branch, Center for Military Psychiatry and Neurosciences, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA. FAU - Wilder, Donna M AU - Wilder DM AD - Blast-Induced Neurotrauma Branch, Center for Military Psychiatry and Neurosciences, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA. FAU - Long, Joseph B AU - Long JB AD - Blast-Induced Neurotrauma Branch, Center for Military Psychiatry and Neurosciences, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA. FAU - Arun, Peethambaran AU - Arun P AD - Blast-Induced Neurotrauma Branch, Center for Military Psychiatry and Neurosciences, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA. LA - eng GR - Military Operational Medicine Research Program at the United States of America Medical Re-search and Development Command/ PT - Journal Article DEP - 20221004 PL - Switzerland TA - Brain Sci JT - Brain sciences JID - 101598646 PMC - PMC9599907 OTO - NOTNLM OT - blast injury OT - circadian rhythm OT - gene expression OT - melatonin OT - pineal gland COIS- The authors declare no conflict of interest. EDAT- 2022/10/28 06:00 MHDA- 2022/10/28 06:01 PMCR- 2022/10/04 CRDT- 2022/10/27 01:11 PHST- 2022/09/03 00:00 [received] PHST- 2022/09/26 00:00 [revised] PHST- 2022/09/30 00:00 [accepted] PHST- 2022/10/27 01:11 [entrez] PHST- 2022/10/28 06:00 [pubmed] PHST- 2022/10/28 06:01 [medline] PHST- 2022/10/04 00:00 [pmc-release] AID - brainsci12101340 [pii] AID - brainsci-12-01340 [pii] AID - 10.3390/brainsci12101340 [doi] PST - epublish SO - Brain Sci. 2022 Oct 4;12(10):1340. doi: 10.3390/brainsci12101340.