Fluctuating levels of estradiol and progesterone during the estrous cycle may induce structural changes in several brain nuclei including the hippocampus, where some neurons express estrogens receptors [1-3]. Nitric oxide plays a wide range of functions in the nervous system generally by acting as a neurotransmitter-like molecule that can contribute to both anterograde and retrograde signalling at the synapse. It has been demonstrated that long-term treatments with estradiol in ovariectomized females and with testosterone in castrated males induce neuronal nitric oxide synthase (nNOS) expression in rat hypothalamus [4-5], whereas changes in nNOS immunoreactivity or in associated NADPH-diaphorase activity were observed both in hypothalamus [6] and in the amygdala [7-8] during different phases of estrous cycle [for a review see 9]. Estradiol could induce nNOS expression in several brain regions in rodents. Therefore, to clarify if the hippocampal NO producing system is a target for gonadal hormones in physiological conditions, we have performed a comparison between two months old intact female and male mice in the expression on nNOS in the hippocampus. Moreover, we have investigated the effects of estrous cycle in the expression of nNOS immunoreactivity on two months old intact female mice. Immunoreactive cells were observed in all the hippocampal subregions: the higher number was detected in the pyramidal layer of CA1 region and in polymorph layer of dentate gyrus. Comparing proestrus female mice with male mice we observed a significantly dimorphism in the number of nNOS positive cells: female mice show a higher number of nNOS-immunoreactive elements in all hippocampal subregions. In the female, the number of nNOS positive neurons fluctuates during the estrous cycle, reaching its peak during proestrus and metaestrus, but these variations were statistically significant only in CA2 region, that is a hippocampal region with fewer cells. In conclusions, our data demonstrate the presence of a sexually dimorphic population of nNOS positive neurons all over the hippocampus. This population is larger in females than in males, and the estrous cycle is playing a non-significant role for the expression of nNOS in the hippocampus. Sexually dimorphic structures or systems that are larger in females than in males are a minority within the rodent brain (i.e. locus coeruleus, AVPV) and the development of these structures is probably under the control of androgens and androgen receptors. Further studies should clarify the mechanisms that are influencing this sex dimorphism in the mouse hippocampus.
Sexual dimorphism and estrous cycle effects on nitrinergic system in mouse hippocampus
GOTTI, STEFANO;MARTINI, MARIANGELA;VIGLIETTI, Carla Maria;PANZICA, Giancarlo
2007-01-01
Abstract
Fluctuating levels of estradiol and progesterone during the estrous cycle may induce structural changes in several brain nuclei including the hippocampus, where some neurons express estrogens receptors [1-3]. Nitric oxide plays a wide range of functions in the nervous system generally by acting as a neurotransmitter-like molecule that can contribute to both anterograde and retrograde signalling at the synapse. It has been demonstrated that long-term treatments with estradiol in ovariectomized females and with testosterone in castrated males induce neuronal nitric oxide synthase (nNOS) expression in rat hypothalamus [4-5], whereas changes in nNOS immunoreactivity or in associated NADPH-diaphorase activity were observed both in hypothalamus [6] and in the amygdala [7-8] during different phases of estrous cycle [for a review see 9]. Estradiol could induce nNOS expression in several brain regions in rodents. Therefore, to clarify if the hippocampal NO producing system is a target for gonadal hormones in physiological conditions, we have performed a comparison between two months old intact female and male mice in the expression on nNOS in the hippocampus. Moreover, we have investigated the effects of estrous cycle in the expression of nNOS immunoreactivity on two months old intact female mice. Immunoreactive cells were observed in all the hippocampal subregions: the higher number was detected in the pyramidal layer of CA1 region and in polymorph layer of dentate gyrus. Comparing proestrus female mice with male mice we observed a significantly dimorphism in the number of nNOS positive cells: female mice show a higher number of nNOS-immunoreactive elements in all hippocampal subregions. In the female, the number of nNOS positive neurons fluctuates during the estrous cycle, reaching its peak during proestrus and metaestrus, but these variations were statistically significant only in CA2 region, that is a hippocampal region with fewer cells. In conclusions, our data demonstrate the presence of a sexually dimorphic population of nNOS positive neurons all over the hippocampus. This population is larger in females than in males, and the estrous cycle is playing a non-significant role for the expression of nNOS in the hippocampus. Sexually dimorphic structures or systems that are larger in females than in males are a minority within the rodent brain (i.e. locus coeruleus, AVPV) and the development of these structures is probably under the control of androgens and androgen receptors. Further studies should clarify the mechanisms that are influencing this sex dimorphism in the mouse hippocampus.
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