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Interaction between Nicotine and Estradiol in Regulation of Gene Expression in Substantia Nigra (SN) in Animal Model of Parkinson's Disease (PD)
Author(s) -
Serova Lidia I,
Nostramo Regina,
Maharjan Shreekrishna,
Sabban Esther L
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.963.5
Subject(s) - endocrinology , medicine , tyrosine hydroxylase , substantia nigra , parkinson's disease , estradiol benzoate , striatum , dopamine , tryptophan hydroxylase , ovariectomized rat , mptp , nicotine , chemistry , dopaminergic , estrogen , receptor , serotonin , serotonergic , disease
The incidence of PD is two fold higher in men than in women. Nicotine (N), which reduces the risk of PD, exhibits sex specific effects. We found that injections of estradiol benzoate (EB) to ovariectomized (OVX) rats change the sensitivity of GTP cyclohydrolase I (GTPCH), the rate‐limiting enzyme for biosynthesis of essential co‐factor for tyrosine hydroxylase (TH), to N. We hypothesize that N and EB have interactive effects on physiology of SN in rats with PD at the level of regulation of GTPCH gene. PD rats were generated by infusion of 6‐OHDA in striatum of OVX rats. The control group received ascorbic acid. 6‐OHDA rats were injected with EB or vehicle (V) once daily for 13 days. EB or V treated rats were divided into two subgroups and from 14 th day, in addition to EB or V, were administered saline or N every 12 hrs. Rats with 6‐OHDA lesions developed forelimb and sensory‐motor deficits while those with EB itself, and in combination with N, improved apomorphine induced rotation behavior. TH and GTPCH mRNA levels were lower in the SN of 6‐OHDA rats compared to controls. N restored both mRNAs in SN only in EB treated rats, with significant interactive effects for GTPCH mRNA. The improvement might be mediated by regulation of nAChR subtype expression. Significant interactive effects of N and EB were found on mRNA levels of α3, α6, α7 subunits of nAChR in SN of the PD rats. Supported by American Parkinson Disease Association.