Perinatal walnut-enriched diet partially rescues mitochondrial dysfunction, neuroinflammation, and behavioral...

Developmental manganese (Mn) exposure is linked to persistent neurobehavioral deficits, yet dietary mitigation strategies remain underexplored. We tested whether a walnut-enriched diet (WED) administered across the perinatal window attenuates Mn-induced biochemical, molecular, and behavioral effects in rats. Pregnant Wistar dams were assigned from gestational day 0 to postnatal day 21 to one of six groups: control, MnCl₂, WED, WED//MnCl₂ (WED before birth then Mn), MnCl₂//WED (Mn before birth then WED), and WED+MnCl₂ (concurrent). Behavioral endpoints (Y-maze spontaneous alternation; elevated plus maze) and biochemical assays (blood Mn, TNF, IL-1β, COX-2, iNOS, and AChE) were assessed in offspring. DNMT3A, H2AX, BDNF, and OPA1 were quantified by densitometry in the prefrontal cortex and hippocampus. Analyses used per-litter means as the experimental unit (behavior: two pups/dam averaged; N=5 litters/group; biochemical/molecular: one pup/dam; N=5/3). Developmental Mn exposure markedly increased whole-blood (and brain) Mn and elevated peripheral Pro-inflammatory markers (TNF, IL-1β, COX-2, and iNOS), with concomitant reductions in BDNF and AChE activity and alterations in H2AX and DNMT3A. Behaviorally, Mn exposure impaired spatial alternation and reduced open-arm exploration in the EPM. Concurrent maternal WED (WED+MnCl₂) partially ameliorated these effects, reducing blood Mn accumulation, attenuating inflammatory responses, improving Y-maze and EPM performance, and restoring BDNF/AChE toward control levels. In this perinatal Wistar rat model, maternal walnut enrichment confers a reproducible, partial protective effect against developmental Mn neurotoxicity and warrants further mechanistic and translational investigation.