Novel roles of neurohypophyseal hormones and biological active substances on brain function in genetic animal model

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Neurohypophyseal hormones (vasopressin and oxytocin) are produced in the neurosecretory cells in the paraventricular and supraoptic nuclei of the hypothalamus, and they are secreted into the systemic circulation from the terminals of the posterior pituitary gland. Vasopressin is known to be anti-diuretic hormone and oxytociin s involved in the delivery and milk-ejection reflex. Recently, we succeeded to generate vasopressin-GFP transgenic rats and oxytocin-CFP transgenic rats. Under fluorescent microscopy we can observe green fluorescence in vasopressin-secreting neurons and blue fluorescence in oxytocin-secreting neurons. The obtained results are as follow. (1) The vasopressin-GFP fusion gene showed exaggerated response to salt loading without disturbance of body fluid homeostasis in the transgenic rats. (2) The GFP fluorescence was distributed in not only the hypothalamo-neurohypophyseal system but also several brain areas such as the locus coeruleus in colchicines-treated vasopressin-GFP transgenic rats. (3) The gene expression of GFP as well as vasopressin and Per1, 2 in the suprachiasmatic nucleus showed circadian rhythm. (4) It was useful to examine the effects of novel peptides on isolated vasopressin-GFP neuron, by using whole-cell patch-clamp technique. (5) The GFP fluorescence in the posterior pituitary gland was monitored by online GFP-monitoring system. Next, we make a plan to generate double transgenic (vasopressin-GFP and oxytocin-CFP) rats.