Abstract
The LC is the major source of NA innervation in the entire brain. In order to make clear the functions of the LC, we established a method to destroy selectively the NA neurons in the LC. Transgenic mice were used that expressed hIL2R driven by the DBH promoter. After injection of the immunotoxin (anti-hIL2R antibody conjugated with Psudomonas exotoxin) into the LC of a male transgenic mouse, the NA neurons were almost entirely ablated in the LC. After lipopolysaccharide (LPS) injection intraperitoneally (ip), the number of Fos-immunoreactive neurons increased dramatically in various brain regions in control animals. In animals whose LC had been destroyed, Fos expression was reduced markedly in the cortex, preoptic and hypothalamic areas as well as amygdaloid nuclei. LPS injection ip elicited marked increase in plasma ACTH in control animals, and this increase was not attenuated in the LC-ablated animals. In the elevated plus-maze, the ratio of the number of open arm entry to the total number of entry became increased in the LC-ablated animals in comparison with that in the controls.These results suggest differential roles of the LC in the neuroendocrine and behavioral responses. We are currently studying whether estrogen may modulate the effects of the LC using female mice with or without estradiol supplementation. [J Physiol Sci. 2007;57 Suppl:S75]
