Fructose -induced maternal metabolic syndrome leads to cerebral oxidative stress, neuroinflammation and neurobehavioral impairments in offspring

Abstract

Since fructose (F) consumption has been linked to the aetiology of metabolic syndrome (MetS), we studied the implications of long- term effects of F consumption by dams on rat offspring neurode- velopment and neurobehavior. Two-month-old Wistar rats were fed standard chow and drank water (control, C) or 20% F (ad libitum) for 10 weeks before mating and throughout pregnancy and lactation. In dams, macronutrient and caloric intake were calculated and blood samples were collected for biochemical analysis. At postnatal day 1 (PN1) oxidative and inflammatory brain status were evaluated in male (♂) and female (♀) pups. The remaining litters (reduced to 8 pups with equal sex ratios) were reassigned to a nursing dam from the C group (NC) or from the F group (NF). Offspring were evaluat- ed for sensorimotor reflexes, reciprocal social interaction, memory retention, novel object recognition and nociception. A p value <0.05 was regarded as statistically significant. F consumption in dams in- duced MetS, increased caloric and carbohydrate intake and reduced protein and fat consumption. Weight, waist circumference and fat % were also higher in F dams. At PN1, ♀ from the F group showed enhanced lipid peroxidation (TBARS) levels, elevated catalase ac- tivity and increased superoxide dismutase protein expression in the whole brain. Neuroinflammation was corroborated by increased pro- tein expression of cyclooxygenase 2. The acquisition of developing milestones was delayed in ♀ from F-NC and F-NF groups. In com- parison with C-NC litter, aggressive social behavior increased while memory retention and nociception were reduced in offspring from F-NC. The ability of recognizing a previously presented stimulus was affected only in ♂ from the F-NC group. These findings suggest that F-induced maternal MetS results in offspring neurodevelopmen- tal delay and neurobehavioral changes probably associated with early brain oxidative stress and inflammation. Interestingly, offspring gender differences were noted