Afferent pathways to the orexinergic neurons that involved in the defense response against stressor

54

Abstracts

from brain, spinal cord to peripheral nerve. I will briefly exemplify how we can track autonomic failure, focusing on sudomotor and adrenergic evaluation and finally, how we can harness known autonomic physiology to enhance treatment of orthostatic hypotension. Sudomotor failure can be due to lesions of the brain, spinal cord, autonomic ganglia or peripheral nerve. The pattern of anhidrosis on the thermoregulatory sweat test (TST) can provide insights to the site of the lesion. The postganglionic axon can be evaluated using the quantitative sudomotor axon reflex test (QSART). Combining the 2 tests can define the site (preganglionic vs postganglionic) of the lesion. Baroreflex failure is responsible for orthostatic hypotension (OH) and a fixed heart rate. It is possible to separately evaluate the vagal and adrenergic components of the baroreflex in the clinical autonomic laboratory. The vagal component of the baroreflex is evaluated by relating heart period to BP change. The adrenergic component can be quantitated by evaluating BP recovery indices. Finally, by enhancing ganglionic neurotransmission, it has been possible to define strategies to alleviate or reduce OH without aggravating supine hypertension. This has been achieved by the use of a cholinesterase inhibitor that increases the safety factor of ganglionic neurotransmission. doi:10.1016/j.autneu.2007.06.078

I-3B-02 Afferent pathways to the orexinergic neurons that involved in the defense response against stressor Wei Zhang a , Takeshi Sakurai c , Yasuichiro Fukuda b , Tomoyuki Kuwaki a,b a Department of Molecular and Integrative Physiology, Graduate School of Medicine Chiba University, Chiba, Japan b Department of Autonomic Physiology, Graduate School of Medicine Chiba University, Chiba, Japan c Department of Pharmacology, University Tsukuba, Japan We have previously shown that the defense response against stressor was attenuated in prepro-orexin knockout mice (Am J Physiol 285:R581, 2003) and orexin neuron-ablated mice (Am J Physiol 290:R1654, 2006) and proposed that orexin plays as a master switch to elicit multiple efferent pathways of the defense response (Autonom Neurosci 126: 139, 2006). However, where the afferent information of stressor comes from to the orexin neurons? Anatomical study has shown that several brain regions innervate to the orexin neuron. Of these regions, amygdale and bed nucleus of stria terminalis (BNST) are thought to be involved in the control of emotion. In this study, we examined possible contribution of the amygdala and the BNST as one of the afferent nuclei to activate orexinergic neurons. We used orexin–ataxin transgenic mice, almost all of the orexinergic neurons were ablated by expression of orexin-promotor driven neurotoxin, ataxin-3. At first, we explored brain regions in the wild-type mice to find the site where electrical simultaneous

increases in blood pressure, heart rate, respiratory frequency and tidal volume. The most effective sites are located in the amygdale and the BNST. Second, In urethane-anesthetized mice, a GABA-A receptor antagonist, bicuculline (0.1–10 mM in 20 nl), was microinjected into the amygdala or BNST. Measured parameters were blood pressure, heart rate, and respiratory frequency. In amygdala, bicuculline induced longlasting and dose-dependent increases in all the parameters in the wild-type mice. However, in orexin transgenic mice, changes were scarcely seen even in the highest dose. In BNST, in the orexin transgenic mice, changes in minute ventilation and blood pressure were smaller than those in the wild-type mice. In an immunohistochemical study, we confirmed that microinjection of bicuculline to the amygdala or BNST induced c-fos expression in the orexinergic neurons. The present study may be summarized as the following three points: one, electrical stimulation to the amygdala and the BNST induced a simultaneous rise in blood pressure, heart rate, respiratory frequency, and tidal volume in the wild-type mice. Two, cardiorespiratory changes were significantly smaller in orexin neuron ablated mice than in the wild-type mice when the amygdala or the BNST were stimulated by microinjection of bicuculline. Three, in the wild-type mice, chemical stimulation to the amygdale or the BNST induced c-fos expression in the orexin neurons. We conclude that the amygdala and BNST constitute one of the afferent pathways to the orexinergic neurons that involved in the defense response against stressor. doi:10.1016/j.autneu.2007.06.079

I-3B-03 A case of leptomeningeal amyloidosis associated with TTR Ala25Thr without somatic or autonomic peripheral neuropathy Yuko Shimizu a, Megumi Takeuchi a, Miyuki Matsumura a, Takahiko Tokuda b, Koichi Hagiwara c, Toru Iwaki c, Junichi Kira c, Makoto Iwata a a Department of Neurology, Tokyo Women's Medical University School of Medicine, Japan b Department of Neurology, Kyoto Prefectural University of Medicine, Japan c Department of Neurology, Neurological Institute, Graduate School of Medicine, Kyushu University, Japan d Department of Neuropathology, Neurological Institute, Graduate School of Medicine, Kyushu University, Japan Familial amyloidotic polyneuropathy is an autosomal dominant inherited disease that is usually caused by mutation of the transthyretin (TTR) gene, and characterized by systemic amyloid deposition in the visceral organs, as well as peripheral somatic and autonomic nerve tissues. It causes progressive autonomic dysfunction including syncope, orthostatic hypotension, neurogenic bladder, impotence and gastrointestinal disturbance. The peripheral neuropathy is generally sensory