Rotational TBI causes neuronal stress and changes in the monoamine and galanin systems.

Abstract

Traumatic brain injury (TBI) is frequently followed by persistent affective symptoms. Dysregulation of monoaminergic and galanin signalling has been implicated but it is unclear whether such changes generalize across distinct biomechanical injury modes. Here we examined a rotational head-acceleration model of mild-moderate injury and directly compared radioactive in situ hybridization (rISH) with a non-radioactive method, alongside immunohistochemistry (IHC), in adult male rats. We quantified transcripts and proteins/peptides of tyrosine hydroxylase (TH), tryptophan hydroxylase-2 (TPH2), and galanin in locus coeruleus (LC) and dorsal raphe nucleus (DRN) and assessed the neuronal stress marker activating transcription factor-3 (ATF3). rISH revealed a rapid, bilateral rise of TH and galanin mRNA in LC at one day post-injury (dpi) and transient increases of TPH2 and galanin mRNA at 1 dpi in mid-DRN. Non-radioactive ISH confirmed these patterns, although modest temporal differences were observed. Peptide measurements showed a similar pattern of increase as their transcripts: TH- and galanin-immunoreactivity in LC increased at 3 dpi, and galanin also rose at 7 dpi in DRN, while TPH2 remained stable. Finally, ATF3 was robustly induced in LC neuronal nuclei at 1 dpi and remained elevated thereafter, indicating activation of a conserved stress response and possible axonal injury. These findings demonstrate that rotational head acceleration triggers selective, time-dependent modulation of monoaminergic and galanin signalling - paralleling prior blast models and confirm ATF3 as an informative marker of injury-activated neuronal states. The concordance across injury models highlights the monoamine and galanin systems as translatable targets for mitigating post-injury affective disturbances.