Background: Traumatic neuronal injury (TNI), a type of traumatic brain injury (TBI), features apoptosis of cortical neurons. Knowing that docosahexaenoic acid (DHA) is enriched in the neuronal cell membranes and related to brain function, we aimed to study the mechanism behind the effect of DHA on TNI model neurons.

Methods: Neurons were derived from Sprague-Dawley rats and a TNI model was established by using a rotating scribe injury device. Four experimental groups were set up based on neuronal injury and DHA concentration, namely the Control, TNI, TNI + DHA-25, and TNI + DHA-50 groups. The cell morphology, toxicity and neuron apoptosis were assessed by means of light microscopy, lactate dehydrogenase (LDH) release assessment, and terminal-deoxynucleotidyl transferase-mediated nick end labeling (TUNEL) assay, respectively. Protein levels of sorcin (SRI), activating transcription factor 6 (ATF6), glucose-regulated protein 78 (GRP78), C/Ebp-homologous protein (CHOP), cleaved-caspase-12 (C-Cas-12) and presenilin 2 (PSEN2) were determined by western blotting. PSEN2 overexpression plasmid and short hairpin RNA against SRI (shSRI) were used for transfection. In the transfection experiment, neurons were assigned into six groups, namely TNI, TNI + DHA-50, short hairpin RNA for negative control (shNC) + Vector, PSEN2, shSRI, and PSEN2 + shSRI groups, and the latter four groups were treated with TNI + DHA. PSEN2 and SRI mRNA levels were measured by quantitative real-time polymerase chain reaction (qRT-PCR). Cytotoxicity-, apoptosis- and endoplasmic reticulum stress (ERS)-related proteins were examined in the neurons.

Results: DHA at a dose of 50 μM attenuated TNI-induced neuronal injury, cell toxicity (p < 0.001), cell apoptosis (p < 0.001), and levels of ERS-related proteins (ATF6, GRP78, CHOP and C-Cas-12) (p < 0.001), PSEN2 and SRI in neurons (p < 0.001). Besides, 50 μM of DHA regulated cell toxicity, cell apoptosis and ERS-related proteins by modulating the interaction between PSEN2 and SRI in neurons (p < 0.05).

Conclusions: DHA mitigates neuron apoptosis induced by SRI-activated ERS via targeting PSEN2.