Reduced hippocampal dendritic spine density and BDNF expression following acute postnatal exposure to di(2-ethylhexyl) phthalate in male Long Evans rats.

Catherine A Smith,Matthew R Holahan,Cheryl Mccormick

doi:10.1371/journal.pone.0109522

Catherine A Smith, Matthew R Holahan + Show 1 more

Open Access

https://doi.org/10.1371/journal.pone.0109522

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Journal: PloS one	Publication Date: Oct 8, 2014
Citations: 101	License type: CC BY 4.0

Affiliation: Carleton University

Abstract

Early developmental exposure to di(2-ethylhexyl) phthalate (DEHP) has been linked to a variety of neurodevelopmental changes, particularly in rodents. The primary goal of this work was to establish whether acute postnatal exposure to a low dose of DEHP would alter hippocampal dendritic morphology and BDNF and caspase-3 mRNA expression in male and female Long Evans rats. Treatment with DEHP in male rats led to a reduction in spine density on basal and apical dendrites of neurons in the CA3 dorsal hippocampal region compared to vehicle-treated male controls. Dorsal hippocampal BDNF mRNA expression was also down-regulated in male rats exposed to DEHP. No differences in hippocampal spine density or BDNF mRNA expression were observed in female rats treated with DEHP compared to controls. DEHP treatment did not affect hippocampal caspase-3 mRNA expression in male or female rats. These results suggest a gender-specific vulnerability to early developmental DEHP exposure in male rats whereby postnatal DEHP exposure may interfere with normal synaptogenesis and connectivity in the hippocampus. Decreased expression of BDNF mRNA may represent a molecular mechanism underlying the reduction in dendritic spine density observed in hippocampal CA3 neurons. These findings provide initial evidence for a link between developmental exposure to DEHP, reduced levels of BDNF and hippocampal atrophy in male rats.

Highlights

Phthalates are synthetically derived chemicals widely used in many common consumer plastic products [1]
No differences in spine density on basal or apical dendrites of CA1 neurons or basal dendrites on DG granule cells were found between di(2-ethylhexyl) phthalate (DEHP)-treated male and female rats when compared to controls of the same gender (p.0.05; Figure 3B; 4B; 5B)
The present study evaluated alterations in dorsal hippocampal dendritic morphology, and Brain-derived neurotrophic factor (BDNF) and caspase-3 mRNA expression following exposure to a low dose of DEHP during early postnatal development in male and female rats

Summary

Introduction

Phthalates are synthetically derived chemicals widely used in many common consumer plastic products [1]. They are not chemically bound to plastic polymers and are released into the environment [2,3]. Animal toxicity studies have shown severe defects in male reproductive organs following early life exposure to phthalates in animals and humans, such as undescended testes [1,6,7,8]. Reduced anogential distance has been observed in human studies, with an inverse relationship between maternal exposure to phthalates and anogential distance in male infants [8]

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