Elsevier

Neuroscience

Volume 159, Issue 3, 31 March 2009, Pages 940-950
Neuroscience

Behavioural Neuroscience
Estradiol prevents ozone-induced increases in brain lipid peroxidation and impaired social recognition memory in female rats

https://doi.org/10.1016/j.neuroscience.2009.01.047Get rights and content

Abstract

There is increasing concern about the neurodegenerative and behavioral consequences of ozone pollution in industrialized urban centers throughout the world and that women may be more susceptible to brain neurodegenerative disorders. In the present study we have investigated the effects of chronic (30 or 60 days) exposure to ozone on olfactory perception and memory and on levels of lipid peroxidation, α and β estrogen receptors and dopamine β-hydroxylase in the olfactory bulb in ovariectomized female rats. The ability of 17β-estradiol to prevent these effects was then assessed. Results showed that ozone exposure for 30 or 60 days impaired formation/retention of a selective olfactory recognition memory 120 min after exposure to a juvenile stimulus animal with the effect at 60 days being significantly greater than at 30 days. They also showed impaired speed in locating a buried chocolate reward after 60 days of ozone exposure indicating some loss of olfactory perception. These functional impairments could all be prevented by coincident estradiol treatment. In the olfactory bulb, levels of lipid peroxidation were increased at both 30- and 60-day time-points and numbers of cells with immunohistochemical staining for α and β estrogen receptors, and dopamine β-hydroxylase were reduced as were α and β estrogen receptor protein levels. These effects were prevented by estradiol treatment. Oxidative stress damage caused by chronic exposure to ozone does therefore impair olfactory perception and social recognition memory and may do so by reducing noradrenergic and estrogen receptor activity in the olfactory bulb. That these effects can be prevented by estradiol treatment suggests increased susceptibility to neurodegenerative disorders in aging women may be contributed to by reduced estrogen levels post-menopause.

Section snippets

Animals

Animals were treated in accordance with the guidelines and requirements of the World Medical Association Declaration of Helsinki and those of the Ethical Committee of the Faculty of Medicine at the Universidad Nacional Autónoma de México. The number of animals used and the animals’ suffering was minimized. Adult virgin female Wistar rats from our colony were used as subjects (n=180); plus 60 that were juveniles used as test stimuli giving a total of 240. The adults weighed 263.56 g±13.8 g and

Social recognition memory and olfactory perception

There was an overall significant difference between the investigation times across treatments (F2,49=40.38, P<0.0013-way ANOVA) and a significant interaction between investigation times and estrogen (F2,49=3.83, P=0.028). Overall there was a significant effect of E2 compared with other treatments (F1,50=7.17, P=0.01) and of the duration of ozone exposure (F1,50=9.85, P<0.001)—i.e. 60-day ozone exposure produced a greater impairment than 30-day exposure. There was also an interaction between

Discussion

Our results clearly show that ozone inhalation for periods of either 30 days or 60 days caused oxidative stress damage in the brain, as measured by a dramatic increase of LPO levels in the olfactory bulb. Long term estrogen administration was able to maintain levels of LPO at those seen in control animals, providing further experimental support for the neuroprotective effects of 17-β E2 (Dluzen, 2000). A functional consequence of the ozone exposure was to interfere with the long-term

Acknowledgments

This research was supported by DGAPA and CONACYT (grant # IN216907, 24,784-M, and IN215408 to S.R.-A.) K.M.K. was supported by BBSRC in the UK. The authors are grateful to Gabino Borgonio and Mariana Angoa for their technical assistance, Mrs. Josefina Bolado for preparation of the manuscript and Dr. Anne Segonds-Pichon (a professional statistician) for analysis of the behavioral results.

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