Protein expression in the nucleus accumbens of rats exposed to developmental vitamin D deficiency

Abstract

Introduction: Developmental vitamin D (DVD) deficiency is a candidate risk factor for schizophrenia. Animal models have confirmed that DVD deficiency is associated with a range of altered genomic, proteomic, structural and behavioural outcomes in the rat. Because the nucleus accumbens has been implicated in neuropsychiatric disorders, in the current study we examined protein expression in this region in adult rats exposed to DVD deficiency

Methods: Female Sprague Dawley rats were maintained on a vitamin D deficient diet for 6 weeks, mated and allowed to give birth, after which a diet containing vitamin D was reintroduced. Male adult offspring (n = 8) were compared to control male (n = 8). 2-D gel electrophoresis-based proteomics and mass spectroscopy were used to investigate differential protein expression.

Results: There were 35 spots, mapped to 33 unique proteins, which were significantly different between the two groups. Of these, 22 were down-regulated and 13 up-regulated. The fold changes were uniformly small, with the largest FC being -1.67. Within the significantly different spots, three calcium binding proteins (calbindin1, calbindin2 and hippocalcin) were altered. Other proteins associated with DVD deficiency related to mitochondrial function, and the dynamin-like proteins.

Conclusions: Developmental vitamin D deficiency was associated with subtle changes in protein expression in the nucleus accumbens. Disruptions in pathways related to calcium-binding proteins and mitochondrial function may underlie some of the behavioural features associated with animal models of developmental vitamin D deficiency.

Figure 1. Altered proteins in the nucleus accumbens in adult DVD-deficient and control male rats.

Red circles indicate increased spots, blue circles indicate spots reduced in the average gel in DVD animals.

Figure 2. Network analysis of the proteins assembled by Ingenuity Pathway Analysis.

Proteins symbols in red were up-regulated, while green were down-regulated. Hub proteins not significantly dysregulated in the study are shown as clear. The proteins with calcium-related functions are annotated (Fx).