Prenatal treatment with metronidazole induces cerebellar folia alteration in guinea pig fetuses

Author:

Capo Ivan1ORCID,Milenkovic Ivan2,Capo Natasa3,Stilinovic Nebojsa4ORCID,Vukmirovic Sasa4ORCID,Teofilovic Branislava5ORCID,Petkovic Branka6ORCID,Sekulic Slobodan7

Affiliation:

1. Department of Histology and Embryology, Faculty of Medicine, University of Novi Sad, Novi Sad, Serbia + Center for Medical and Pharmaceutical Investigations and Quality Control, Faculty of Medicine, University of Novi Sad, Novi Sad, Serbia

2. Department of Neurology, Medical University of Vienna, Vienna, Austria

3. Faculty of Medicine, University of Novi Sad, Novi Sad, Serbia + Oncology Institute of Vojvodina, Sremska Kamenica, Serbia

4. Department of Pharmacology, Toxicology and Clinical Pharmacology, Faculty of Medicine, University of Novi Sad, Novi Sad, Serbia

5. Department of Pharmacy, Faculty of Medicine, University of Novi Sad, Novi Sad, Serbia

6. Department of Neurophysiology, Institute for Biological Research “Siniša Stanković” - National Institute of the Republic of Serbia, University of Belgrade, Serbia

7. Department of Neurology, Faculty of Medicine, University of Novi Sad, Novi Sad, Serbia

Abstract

The most sensitive period in brain development is during prenatal life. The use of antibiotics in pregnancy is still controversial. Recent studies revealed the high neurotoxic potential of the antibiotic and antiprotozoal medication, metronidazole. However, there are insufficient data from animal studies about prenatal treatment effects. We investigated the effect of prenatal treatment with metronidazole on cerebellar development in guinea pigs. Treatment with metronidazole was performed from the 42nd to the 49th day of gestation. On the 50th day of pregnancy, all dams were killed, and the cerebella of the fetuses were analyzed. Gross cerebellar changes characterized by malposition of the folia with partial atrophy were found in 12 of 19 fetuses in the experimental group, but in none of 20 control fetuses that received saline. The most affected were folia VII with depletion of the areal fraction of the external granular layer, molecular layer and the internal granular layer. Purkinje cells displayed cell distortion with loss of normal dendritic polarity. The investigation revealed cell depletion, with a disturbance of the cytoarchitectonic of the cerebellar cortex and folia alteration.

Funder

Ministry of Education, Science and Technological Development of the Republic of Serbia

Publisher

National Library of Serbia

Subject

General Agricultural and Biological Sciences,General Biochemistry, Genetics and Molecular Biology

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