Effect of sex and estrogens on neuronal activation in an animal model of migraine.
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.


CONCLUSIONS
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.
Headache Science Centre, IRCCS National Neurological Institute C. Mondino Foundation and University of Pavia, Pavia, Italy. rosaria.greco@mondino.it
Rosaria
R
Greco
Cristina
C
Tassorelli
A Stefania
AS
Mangione
Antonella
A
Smeraldi
Marta
M
Allena
Giorgio
G
Sandrini
Giuseppe
G
Nappi
Rossella E
RE
Nappi
D000704:Analysis of Variance; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D003270:Contraceptive Agents / Q000009:adverse effects; D004195:Disease Models, Animal; D004958:Estradiol / Q000009:adverse effects / Q000031:analogs & derivatives; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D008297:Male; D008881:Migraine Disorders / Q000139:chemically induced / Q000188:drug therapy / Q000473:pathology*; D005996:Nitroglycerin / Q000627:therapeutic use; D016761:Oncogene Proteins v-fos / Q000378:metabolism; D010052:Ovariectomy; D051381:Rats; D017207:Rats, Sprague-Dawley; D012727:Sex Characteristics; D014665:Vasodilator Agents / Q000627:therapeutic use
D003270:Contraceptive Agents; D016761:Oncogene Proteins v-fos; D014665:Vasodilator Agents; C074283:estradiol 3-benzoate; D004958:Estradiol; D005996:Nitroglycerin