Postnatal zinc deficiency due to giardiasis disrupts hippocampal and cerebellar development

Abstract

Background

Giardiasis and zinc deficiency have been identified as serious health problems worldwide. Although Zn depletion is known to occur in giardiasis, no work has investigated whether changes occur in brain structures.

Methods

Three groups of gerbils were used: control (1), orogastrically inoculated on day 3 after birth with trophozoites of two isolates of Giardia intestinalis (HGINV/WB) group (2 and 3). Estimates were made at five ages covering: establishment of infection, Giardia population growth, natural parasite clearance and a post-infection age. QuantiChrome zinc assay kit, cresyl violet staining and TUNEL technique were used.

Results

A significant decrease (p<0.01) in tissue zinc was observed and persisted after infection. Cytoarchitectural changes were observed in 75% of gerbils in the HGINV or WB groups. Ectopic pyramidal neurons were found in the cornus ammonis (CA1-CA3). At 60 and 90 days of age loss of lamination was clearly visible in CA1. In the dentate gyrus (DG), thinning of the dorsal lamina and abnormal thickening of the ventral lamina were observed from 30 days of age. In the cerebellum, we found an increase (p<0.01) in the thickness of the external granular layer (EGL) at 14 days of age that persisted until day 21 (C 3 ± 0.3 μm; HGINV 37 ± 5 μm; WB 28 ± 3 μm); Purkinje cell population estimation showed a significant decrease; a large number of apoptotic somas were observed scattered in the molecular layer; in 60 and 90 days old gerbils we found granular cell heterotopia and Purkinje cell ectopia. The pattern of apoptosis was different in the cerebellum and hippocampus of parasitized gerbils.

Conclusion

The morphological changes found suggest that neuronal migration is affected by zinc depletion caused by giardiasis in early postnatal life; for the first time, the link between giardiasis-zinc depletion and damaged brain structures is shown. This damage may explain the psychomotor/cognitive delay associated with giardiasis. These findings are alarming. Alterations in zinc metabolism and signalling are known to be involved in many brain disorders, including autism.

Author summary

Giardia intestinalis (Syn. G. duodenalis or G. lamblia), is a protozoan flagellate that parasitizes humans and animals and is transmitted by the ingestion of food or water contaminated with cysts or via person-to-person contact. Causes diarrhoea. Affects children and adults worldwide. Giardiasis is known to have long-term effects. When giardiasis occurs in the first two years of a child’s life, it is associated with stunted growth and psychomotor and cognitive retardation.

Giardiasis and zinc deficiency have been identified as serious health problems worldwide. Although Zn depletion is known to occur in giardiasis, no work has investigated whether changes occur in brain structures.

We modelled Giardia infection in gerbils in the first days of postnatal life and found morphological changes that suggest neuronal migration is affected by zinc depletion caused by giardiasis in early postnatal life.

For the first time, the link between giardiasis-zinc depletion and damaged brain structures is shown. This damage may explain the psychomotor-cognitive delay associated with giardiasis.

Alterations in zinc metabolism and signalling are known to be involved in many brain disorders, including autism.