ABSTRACT
A growing number of studies have identified sex differences in response to general anesthesia; however, the underlying neural mechanisms are unclear. The medial preoptic area (MPA), an important sexually dimorphic structure and a critical hub for regulating consciousness transition, is enriched with estrogen receptor alpha (ERα), particularly in neuronal clusters that participate in regulating sleep. We found that male mice were more sensitive to sevoflurane. Pharmacological inhibition of ERα in the MPA abolished the sex differences in sevoflurane anesthesia, in particular by extending the induction time and facilitating emergence in males but not in females. Suppression of ERα in vitro inhibited GABAergic and glutamatergic neurons of the MPA in males but not in females. Furthermore, ERα knockdown in GABAergic neurons of the male MPA was sufficient to eliminate sex differences during sevoflurane anesthesia. Collectively, MPA ERα positively regulates the activity of MPA GABAergic neurons in males but not in females, which contributes to the sex difference of mice in sevoflurane anesthesia.
Subject(s)
Animals , Female , Male , Mice , Anesthesia , Estrogen Receptor alpha/metabolism , Preoptic Area , Sevoflurane/pharmacology , Sex CharacteristicsABSTRACT
Hypothalamic temperature (Thy) alteration is one of the important stimuli that brings about thermoregulatory measures including the changes in wakefulness and muscular activity. The role of the lateral preoptic area (lPOA) in thermoregulation and sleep is well documented. But it is not known whether the integrity of the lPOA is essential for bringing about the changes in sleep-wakefulness (S-W) and thermoregulation in cold ambient temperature (Ta). Neurotoxic lesion of the lPOA resulted in an increase in wake period and core body temperature (Tb) and no change in Thy. Unlike, normal animals, as reported earlier, there was further increase in Tb of the lPOA lesioned rats on acute cold exposure, but the Thy remained unaltered throughout the 28 days of continued cold exposure. The findings demonstrate that the lPOA lesioned rats have lost the ability to reset Thy which may be necessary for thermoregulation during cold exposure. Moreover, increased wake period lasted only 7 days in lesioned, compared to 14 days in normal animals. Less efficient restoration of Tb, and less prolonged wake period during continued cold exposure, are probably the result of the inability of the lPOA lesioned rats to lower Thy, which is necessary to bring about the thermoregulatory measures.
ABSTRACT
Within the medial preoptic area[MPOA], several cytoarchitectonically defined cell groups are sexually dimorphic in their morphology. Specially, the sexual dimorphic nucleus of the preoptic area[SDN-POA] is reported an example of a morphological sex difference in the rat hypothalamus which is influenced by gonadal steroid hormones. Thus, we detemined the distribution of Galanin-immunoreactive[Gal-I] cells and fibers within MPOA and their morphological response to gonadal steroids which is influenced by gonadectomy or prenatal restosterone treatments were observed. The Gal-I cells were appeared within the medial preoptic area. In the males, the volume and number of Gal-I nerve cell bodies were greater than that of females. But the female which treated prenatal testosterone injection had many Gal-I neurons than infact female. And the males that decreased the volume of gonadal hormone by gonadectomy were decreased the volume and number of Gal-I neurons than that of normal males. These results suggest that galaninergic cells within the medial preoptic area are influenced by gonadal steroid hormone[testosterone] in the regulation of sexually dimorphic function.