Postnatal zinc deficiency due to giardiasis disrupts hippocampal and cerebellar development.

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.

Prenatal Protein Malnutrition Affects the Density of GABAergic Interneurons During Hippocampus Development in Rats.

BACKGROUND: Prenatal protein malnutrition disrupts the pattern of maturation and development of the hippocampus and its neuroanatomy and increases inhibition of the granular cell layer of the fascia dentata. If local gamma-aminobutyric acid inter-neurons are partly responsible for inhibition of the hippocampus, it is reasonable to assume that there may be an increase in the gamma-aminobutyric acid cell population of prenatal protein malnutrition rats. OBJECTIVE: This experimental study was conducted to ascertain the effects of prenatal protein malnutrition on the density of GABAergic interneurons at the cornus ammonis and fascia dentata in rats. METHODS: Animals were investigated under two nutritional conditions: (i) prenatal protein malnutrition group fed 6% protein, and (ii) well-nourished control group fed 25% protein. Using an antibody for gamma-aminobutyric acid, immunoreactive cells (GABAergic) were assessed in the rostral-caudal direction of the dorsal hippocampus at four levels. RESULTS: (i) In 30-day-old rats with prenatal malnutrition, the fascia dentata had an average of 27% more GABAergic cells than the control group; this higher amount was not detectable at 90 days. (ii) There was a significant 18% increase in GABAergic neurons at level 1 of the cornus ammonis at 90 days of age. CONCLUSIONS: There was an increase in the population of interneurons in the fascia dentata and cornus ammonis in prenatal protein malnutrition rats. We conclude that prenatal hypoprotein malnutrition produces changes at 30 days in the fascia dentata. Results suggest that prenatal malnutrition also produces a delay in the programmed chronology of gamma-aminobutyric acid interneurons. Finally, in cornus ammonis, at 90 days of age, prenatal protein malnutrition showed an increase only at level 1; this effect may be evidenced in the long term, despite postnatal rehabilitation.

Purkinje cell density in cerebella of alcoholized and non-alcoholized male rat offspring

The effect of alcohol intake by male rats was evaluated on Purkinje cell morphology and number in their offspring. Forty five male Wistar rats, 45 days old, were used and divided into three groups of 15 rats each: control group (CG), fed with conventional Purina rodent feed (CPRF) and water ad libitum; experimental group (EG), fed with CPRF ad libitum and a mixture of water/ethanol, which represented 36 per cent of kiloclories in food; and an equinergetic intake control group (ECG), which was given CPRF (in grams) and sugar in their drinking water, in order to substitute the energetic value provided by alcohol. Five subgroups (n=3) were created to be used for different treatment periods: 60, 90,120, 150 and 180 days; all groups started treatment period when they were 70 days old. At the end of each treatment period, male rats were mated with nulliparous females not having undergone treatment. Offspring were obtained and studied at 14 and 21 days of age. The Purkinje cells of the cerebella of 14-and 21-day-old offspring belonging to the CG and ECG showed no morphological changes. On the other hand, in 14-day-old offspring belonging to the experimental group of parents alcoholized during 90, 120, and 180 days, a large number of hyperchromatic Purkinje cells were seen, forming zones of cells undergoing a degenerative process. No significant differences in cellular density were determined between the CG and the ECG. When comparing the CG vs. EG and the ECG vs. Eg, significant differences were found in the 14-day-old offspring as well as in the 21-day-old ones with a p<0.05 of rats belonging to parents alcoholized for 90, 120, and 180 days. The results may indicate that there are changes in the germinal plasma of males fue to alcohol of males due to alcohol sunsumption; therefore, reflecting this effect on a drecrease of Purkinje cells and probably on ther cell populations