Omega-3 Fatty Acid Pretreatment Modulates Mitochondrial Quality-Control and PINK1/PARKIN-Related Gene Expression in Acute LPS-Induced Neuroinflammation.

Neuroinflammation contributes to central nervous system injury through interconnected oxidative, glial, apoptotic, and mitochondrial responses. Omega-3 (OM-3) fatty acids are neuroprotective, but their association with mitochondrial quality-control pathways during acute neuroinflammation remains incompletely defined. This study examined the preventive effects of OM-3 pretreatment in a lipopolysaccharide (LPS)-induced neuroinflammation model. Adult female Wistar albino rats (n = 8/group) were randomly assigned to Control, LPS (5 mg/kg, intraperitoneal), LPS + OM-3 (OM-3, 0.5 g/kg/day intraperitoneally for 3 days before LPS), and OM-3 groups. Six hours after LPS administration, brain and cerebellar tissues were evaluated by histopathology, immunohistochemistry (8-OHdG, Cas-3, and GFAP), qRT-PCR for apoptosis-, antioxidant-, mitochondrial biogenesis-, and mitophagy-related transcripts, and biochemical assessment of total antioxidant status (TAS), total oxidant status (TOS), and oxidative stress index (OSI). LPS increased histopathological injury and 8-OHdG, Cas-3, and GFAP immunoreactivity; increased BAX/BCL-2, PINK1, PARKIN, and SNCA transcript levels; reduced PGC-1alpha and NRF2-related antioxidant responses; decreased TAS; and increased OSI. OM-3 pretreatment attenuated many of these changes relative to LPS alone. However, several outcomes remained significantly different from Control, indicating partial rather than complete reversal. Because PINK1 and PARKIN were measured only at the mRNA level, the findings demonstrate modulation of the transcriptional response of mitophagy-related genes and do not establish functional mitophagic flux. In this 6-h acute preventive model, OM-3 pretreatment was associated with partial neuroprotection and modulation of transcriptional markers linked to antioxidant defense and mitochondrial quality Control. Protein-level and flux assays, later time points, and post-injury treatment designs are required before functional restoration of mitophagy or therapeutic efficacy can be concluded.