Impaired structural and functional development of cerebellum following gestational exposure of deltamethrin in rats: role of reelin.

Abstract

Reelin is an extracellular matrix molecule that is involved in the normal development of the cerebellar lamination, Bergmann glial fibres alignment, Purkinje cell monolayer arrangement and granule cell migration. In this study, we have examined the effects of maternal exposure of deltamethrin (DLT), a type II pyrethroid insecticide, on the structural and functional development of rat cerebellum during postnatal life. DLT (0.75 mg/kg body weight, intraperitoneally dissolved in dimethylsulphoxide) was administered in timed pregnant rats during two different gestational time periods, i.e. gestational days of 7-10 and 11-14, respectively. In DLT exposed rats, a significant overexpression of reelin was observed in the cells of the external granule cell layer (EGL) and internal granule cell layer along with an ectopic expression of reelin in the EGL as well as in the migrating granule cells just below the EGL, revealing an arrest of granule cell migration in this zone. Mis-orientation and hypertrophy of the Bergmann glial fibres further hampered the journey of the granule cells to their final destination. Possibly reelin overexpression also caused misalignment of the Purkinje cells and inhibited the neurite growth leading to a significant decrease in the spine density, main dendritic length and width of the dendritic arbour. Thus, it is proposed that the DLT exerts its neurotoxic effects possibly via the intracellular accumulation and low release of reelin leading to an impaired granule cell and Purkinje cell migration, inhibition of neurite outgrowth and reduced spine density. Such impaired cerebellar development leads to motor coordination deficits.

• Authors: Kamendra Kumar, Nisha Patro, Ishan Patro
• Journal: Cellular and molecular neurobiology (Cell Mol Neurobiol) Vol. 33 Issue 5 Pg. 731-46 (Jul 2013) ISSN: 1573-6830 [Electronic] United States
• PMID: 23681596 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cell Adhesion Molecules, Neuronal
• Extracellular Matrix Proteins
• Glial Fibrillary Acidic Protein
• Nerve Tissue Proteins
• Nitriles
• Pyrethrins
• Reelin Protein
• Reln protein, rat
• decamethrin
• Serine Endopeptidases

Topics

• Animals
• Animals, Newborn
• Body Weight (drug effects)
• Cell Adhesion Molecules, Neuronal (metabolism)
• Cerebellum (growth & development, pathology, physiopathology)
• Dendrites (drug effects, metabolism, pathology)
• Extracellular Matrix Proteins (metabolism)
• Female
• Glial Fibrillary Acidic Protein (metabolism)
• Immunohistochemistry
• Male
• Maternal Exposure
• Motor Activity (drug effects)
• Nerve Tissue Proteins (metabolism)
• Neurogenesis (drug effects)
• Nitriles (toxicity)
• Phenotype
• Pregnancy
• Prenatal Exposure Delayed Effects (pathology, physiopathology)
• Purkinje Cells (drug effects, metabolism, pathology)
• Pyrethrins (toxicity)
• Rats
• Rats, Wistar
• Reelin Protein
• Rotarod Performance Test
• Serine Endopeptidases (metabolism)