Felt and expressed needs regarding occupational health services from the perspective of micro-, small and medium-sized enterprises: a scoping review.

It is well known that hypoxia‐inducible transcription factors (HIF‐1α, HIF‐2α) and HIF‐3α activate not only in response to reduced oxygen availability but also under other extreme conditions and coordinate adaptive responses, including metabolic reprogramming, angiogenesis, and neuroprotection. Unlike HIF‐1α and HIF‐2α, HIF‐3α is expressed as multiple splice variants: while some isoforms act as negative regulators of HIF‐1α and HIF‐2α, others retain transcriptional activity and can drive a distinct hypoxic gene program (Merelli et al. ; Sharp and Bernaudin ; Rius et al. ; Butt et al. ). Are there HIFs potentially relevant components of the post‐traumatic stress disorder (PTSD) molecular landscape? Chronic psychological stress is accompanied by signs of oxidative stress and tissue hypoxia, mitochondrial dysfunction, which, in turn, can activate HIF‐dependent pathways (Chen et al. ). There is evidence that PACAP (Pituitary adenylate cyclase‐activating polypeptide) can modulate HIF expression, and HIFs can reciprocally influence PACAP receptor sensitivity (Singh et al. ; Stroth et al. ). At the neurobiological level, PTSD is associated with structural and functional changes in the hippocampus, amygdala, and medial prefrontal cortex (mPFC) (Bisson et al. ; Du et al. ). At the molecular level, the most noticeable change is a reduction in brain‐derived neurotrophic factor (BDNF) levels (a key regulator of neuroplasticity and memory consolidation) (Chen et al. ; Fujii et al. ). BDNF is not synthesized directly in its active form: its precursor, proBDNF, requires enzymatic activation via the tissue plasminogen activator (tPA) system. This system, in turn, is tightly regulated by the inhibitor PAI‐1, whose levels rise during stress and are associated with the suppression of neuroplasticity (Bouarab et al. ; Yang et al. ; Mennesson and Revest ). This raises the possibility of a feedback loop between hypoxic signaling and the PACAP–PAI‐1 axis, which could be of fundamental importance for understanding the molecular basis of PTSD. However, these relationships remain hypothetical for now. This study aims to determine the expression levels of HIF‐1α, HIF‐2α, HIF‐3α, PACAP, and PAI‐1 in the hippocampus and mPFC from intact rats and rats with a PTSD‐like phenotype induced by the single prolonged stress (SPS) protocol (Muhie et al. ). A comparative analysis between the groups will determine whether these molecules undergo coordinated changes in response to SPS stress and assess the potential role of hypoxic signaling in the molecular pathogenesis of PTSD. The results obtained will form the basis for further investigation into the interaction among HIF, PACAP, and PAI‐1 as potential therapeutic targets.