Objective  To explore the effect and mechanism of dietary restriction (DR) on manganese (Mn)-induced neurotoxicity.

  Methods  Forty adult Kunming mice (male : female = 1 : 1) were randomly divided into four groups (10 in each group): control group (25.0 g feed/day and intraperitoneal injection of saline), DR control group (12.5 g feed/day and intraperitoneal injection of saline), Mn exposure group (25.0 g feed/day and intraperitoneal injection of Mn at dose of 200 μmol/kg) and DR intervention group (12.5 g feed/day and intraperitoneal injection of Mn at dose of 200 μmol/kg). The treatments were conducted once a day continuously for 6 weeks. The mice′s weight and blood glucose were measured and their behavioral changes were observed every week. By the end of the treatments, the brain specimens were collected for determinations of brain coefficient, cumulated Mn content, levels of inflammatory factors, and expressions of related proteins.

  Results  In the Mn exposed mice, abnormal behavioral changes were observed; decreased brain coefficient and interleukin 4 (IL-4) but increased tumor necrosis factor-α (TNF-α), inducible nitric oxide synthase (iNOS), protein expression of nuclear factor kappa B (NF-κB), and caspase-8 were detected compared to those in the control mice (all P < 0.05). Decreased brain coefficient, TNF-α, iNOS, NF-κB, and caspase-8 were detected in the Mn exposed mice with DR in comparison with those in the Mn exposed mice with normal feeding (P < 0.05 for all).

  Conclusion  Dietary restriction could play a protective role in Mn-induced neurotoxicity and the effect may be related to inflammation suppression, apoptosis reduction, and autophagy enhancement in mice.