Premium
Effect of Sex and Estrogens on Neuronal Activation in an Animal Model of Migraine
Author(s) -
Greco Rosaria,
Tassorelli Cristina,
Mangione A. Stefania,
Smeraldi Antonella,
Allena Marta,
Sandrini Giorgio,
Nappi Giuseppe,
Nappi Rossella E.
Publication year - 2013
Publication title -
headache: the journal of head and face pain
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.14
H-Index - 119
eISSN - 1526-4610
pISSN - 0017-8748
DOI - 10.1111/j.1526-4610.2012.02249.x
Subject(s) - medicine , endocrinology , central nucleus of the amygdala , area postrema , estrogen , supraoptic nucleus , estradiol benzoate , c fos , premovement neuronal activity , immediate early gene , hypothalamus , nucleus , ventromedial nucleus of the hypothalamus , amygdala , nociception , neuroscience , chemistry , biology , central nervous system , gene expression , ovariectomized rat , receptor , biochemistry , gene
Objective.— In this study, we evaluated the influence of sex and estrogen treatment on nitroglycerin (NTG)‐induced neuronal activation in the rat brain. Background.— Systemic NTG activates cerebral nuclei of rat involved in nociceptive transmission, as well as in neuroendocrine and autonomic functions. These changes are considered relevant for migraine, since NTG consistently induces spontaneous‐like attacks in migraineurs. Methods.— Intact and castrated male and female rats, and castrated female rats treated with estradiol benzoate (or placebo) were injected with NTG and sacrificed after 4 hours. Rats were perfused, and their brains were processed for Fos protein, a marker of neuronal activation. Results.— Data showed a reduced expression of NTG‐induced Fos protein in the paraventricular nucleus (PVH), supraoptic nucleus (SON), and nucleus trigeminalis caudalis (SPVC) of male rats in comparison with female rats. Furthermore, in castrated female rats, NTG‐induced neuronal activation was reduced in PVH, SON, central nucleus of the amygdala (AMI), nucleus tractus solitarius (NTS), area postrema (AP), and SPVC, while in castrated male rats Fos expression was reduced uniquely in the SPVC. Chronic administration of estrogens restored Fos protein expression in PVH, SON, AMI, NTS, AP, and SPVC in castrated female rats. Conclusion.— These data provide a support for the existence of a sexual dimorphism in NTG‐induced neuronal activation, and they prompt a specific model for evaluating and modulating the influence of estrogens upon the cerebral structures implicated in the pathophysiology of migraine.