Preliminary morphological and morphometric study of rat cerebellum following sodium arsenite exposure during rapid brain growth (RBG) period

Toxicology. 2007 May 5;234(1-2):10-20. doi: 10.1016/j.tox.2007.01.024. Epub 2007 Feb 11.

Abstract

The effects of arsenic exposure during rapid brain growth (RBG) period were studied in rat brains with emphasis on the Purkinje cells of the cerebellum. The RBG period in rats extends from postnatal day 4 (PND 4) to postnatal day 10 (PND 10) and is reported to be highly vulnerable to environmental insults. Mother reared Wistar rat pups were administered intraperitoneal injections (i.p.) of sodium arsenite (aqueous solution) in doses of 1.0, 1.5 and 2.0mg/kg body weight (bw) to groups II, III and IV (n=6 animals/group) from PND 4 to 10 (sub acute). Control animals (group I) received distilled water by the same route. On PND 11, the animals were perfusion fixed with 4% paraformaldehyde in 0.1M phosphate buffer (PB) with pH 7.4. The cerebellum obtained from these animals was post-fixed and processed for paraffin embedding. Besides studying the morphological characteristics of Purkinje cells in cresyl violet (CV) stained paraffin sections (10 microm), morphometric analysis of Purkinje cells was carried out using Image Analysis System (Image Proplus software version 4.5) attached to Nikon Microphot-FX microscope. The results showed that on PND 11, the Purkinje cells were arranged in multiple layers extending from Purkinje cell layer (PL) to outer part of granule cell layer (GL) in experimental animals (contrary to monolayer arrangement within PL in control animals). Also, delayed maturation (well defined apical cytoplasmic cones and intense basal basophilia) was evident in Purkinje cells of experimental animals on PND 11. The mean Purkinje cell nuclear area was significantly increased in the arsenic treated animals compared to the control animals. The observations of the present study (faulty migration, delayed maturation and alteration in nuclear area measurements of Purkinje cells subsequent to arsenic exposure) thus provided the morphological evidence of structural alterations subsequent to arsenite induced developmental neurotoxicity which could be presumed to be the underlying basis for some of the functional deficits encountered in the later period of life.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Arsenites / administration & dosage
  • Arsenites / toxicity*
  • Body Weight / drug effects
  • Cell Nucleus / drug effects
  • Cerebellum / drug effects*
  • Cerebellum / growth & development
  • Female
  • Injections, Intraperitoneal
  • Lactation / physiology
  • Pregnancy
  • Purkinje Cells / drug effects*
  • Purkinje Cells / pathology
  • Purkinje Cells / ultrastructure
  • Rats
  • Rats, Wistar
  • Sodium Compounds / administration & dosage
  • Sodium Compounds / toxicity*
  • Time Factors

Substances

  • Arsenites
  • Sodium Compounds
  • sodium arsenite