Brain control for sensing of peripheral blood information and maintenance of body homeostasis

脳による末梢血液情報感知とホメオスタシス維持機構

2017-03-24

2017-03-24

The circumventricular organs (CVOs), including the organum vasculosum of the lamina terminals, subfornical organ, and area postrema, monitor the conditions of blood environment and control the hypothalamo-neurohypophysial system (HNS) and brain center of the autonomic nervous system to maintain homeostasis. 1) TRPV1 sensing peripheral blood-derived information in the sensory circumventricula organs Transient receptor potential vanilloid receptor 1 ion channel (TRPV1) is a polymodal nonselective cation channel and activated by high osmolarity and acidic pH. This study, revealed the localization of TRPV1 at a thick cellular processes of astrocyte to constitute dense network surrounding the vasculature in the CVOs. Furthermore, Fos immunohistochemistry showed astrocytic TRPV1 senses blood- and cerebrospinal fluid-derived information and transmits its information to neighboring brain neurons. Thus, astrocytic TRPV1 in the CVOs is able to monitor directly osmolarity and acid for homeostasis. 2) TRPV1 activates STAT3 signaling and thermoregulatory pathways in the brain The present study shows the involvement of TRPV1 in the CVOs with thermoregulation under inflammation. The TRPV1 activation induces faster proinflammatory responses of STAT3 in the CVOs and thermoregulation related brain regions and induces hypothermia. Furthermore, inhibition of TRPV1 enhances lipopolysaccharide-induced hyperthermia. Thus, astrocytic TRPV1 in the CVOs has an important role in proinflammatory STAT3 activation and thermoregulation. 3) Notch signaling in the hypothalamic-neurohypophysial system The HNS shows structural plasticity to enhance synthesizing of vasopressin and oxytocin at the supraoptic nucleus (SON) and paraventricular nucleus (PVN) and releasing at the neurohypophysis. This study revealed the existence of Notch signaling in the HNS. Notch ligand Delta-like 4 (DLL4) was localized at the axonal terminals and Notch3 at the vasopressin- and oxytocin-containing somato-dendrites in the SON and PVN. In the neurohypophysis, DLL4 was localized at the oxytocin-containing axonal terminals and Notch3 at pituicytes. Chronic osmotic stimulation reduces DLL4 expression at the SON and PVN. Furthermore, both chronic and acute osmotic stimulation promote proteolytic cleavage of Notch3 in the NHS. Thus, activity-dependent Notch signaling may be involved in structural plasticity in the HNS. The circumventricular organs (CVOs), including the organum vasculosum of the lamina terminals, subfornical organ, and area postrema, monitor the conditions of blood environment and control the hypothalamo-neurohypophysial system (HNS) and brain center of the autonomic nervous system to maintain homeostasis.

博士（学術）

京都工芸繊維大学

14303甲第827号

http://hdl.handle.net/10212/2384

eng

ETD

Thesis or Dissertation

Thesis