Summary
To define the physiological roles of Pituitary adenylate cyclase-activating polypeptide (PACAP), we developed PACAP specific receptor (PAC1) transgenic (Tg) mice using the Cre/loxP recombination system. wPAC1 Tg mice, which express the Pac1 transgene in their entire body, showed increased behavioral activity in the dark period of a 12-h light/dark cycle (Zeitegeber time 0 (ZT0) = lights on, ZT12= lights off). LNL-PAC1/CaMKII-Cre double Tg mice (hPAC1 Tg mice), which undergo Cre/loxP recombination in hippocampal nerve cells, expressed the Pac1 transgene in the hippocampus. hPAC1 Tg mice showed increased behavioral activity (150% or more compared to control) in the early dark period (ZT 12–17), which is the most active time for wild type mice. However, there was no change in circadian rhythm. Similar hyperactivity was observed in LNL-PAC1/CaMKII-CreER double Tg mice (ihPAC1 Tg mice) when the mice were treated with tamoxifen to induce Cre/loxp recombination in adulthood. Moreover, immunohistochemical analysis of LNL-PAC1/LNL-Venus/ CaMKII-CreER triple Tg mice treated with tamoxifen, revealed that PAC1 transgene were expressed in hippocampal nerve cells. These results suggest that the expression of the PAC1 transgene, especially in hippocampal nerve cells, may enhance the behavioral activity associated with regular circadian rhythm.
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References
Arimura A (1992) Receptors for pituitary adenylate cyclase-activating polypeptide: comparison with vasoactive intestinal peptide receptors, Trends Endocrinol Metab 3:288–294
Otto C, Hein L, Brede M, Jahns R, Engelhardt S, Grone HJ, Schutz, G (2004) Pulmonary hypertension and right heart failure in pituitary adenylate cyclase-activating cyclase-activating polypeptide type 1 receptor-deficient mice. Circulation 110:3245–3251
Hannibal J, Moller M, Ottersen OP, Fahrenkrug J (2000) PACAP and glutamate are co-stored in the retinohypothalamic tract. J Comp Neurol 418:147–155
Hannibal J, Francoise J, Harriette Nielsen HS, Laurant J, Brabet P, Fahrenkrug J (2001) Dissociation between light-induced phase shift on the circadian rhythm and clock gene expression in mice lacking the pituitary adenylate cyclase activating polypeptide type 1 receptor. J Neuroscience 21:4883–4890
Harrington ME, Hoque S, Hall A, Golombek D, Biello S (1999) Pituitary adenylate cyclase-activating peptide phase shifts circadian rhythms in a manner similar to light. J Neurol. 19:6637–6642
Hashimoto H, Shintani N, Tanaka K, Mori W, Hirose M, Matsuda T, Sakaue M, Miyazaki J, Niwa H, Tashiro F, Yamamoto K, Koga K, Tomimoto S, Kunugi A, Suetake S, Baba A (2001) Altered psychomotor behaviors in mice lacking pituitary adenylate cyclase-activating cyclase-activating polypeptide (PACAP). Proc Natl Acad Sci U.S.A. 98:13355–13360
Kanegae Y, Takamori K, Sato Y, Lee G, Nakai M, Saito I (1996) Efficient gene activation system on mammalian cell chromosomes using recombinant adenovirus producing Cre recombinase. Gene 181:207–212
Kido T, Arata S, Suzuki R, Hosono T, Nakanishi Y, Miyazaki J, Saito I, Kuroki T, Shioda S (2005) The testicular fatty acid binding protein PERF15 regulates the fate of germ cells in PERF15 transgenic mice. Dev Growth Differ. 47:15–24
Masuo Y, Noguchi J, Morita S, Matsumoto Y (1995) Effects of intracere-broventricular administration of pituitary adenylate cyclase-activating polypeptide (PACAP) on the motor activity and reserpine-induced hypothermia in murines. Brain Res. 700:219–226
Masuo Y, Morita M, Oka S, Ishido M (2004) Motor hyperactivity caused by a deficit in dopaminergic neurons and the effects of endocrine disruptor: study inspired by the physiological roles of PACAP in the brain. Regul Pept 123:225–234
Nielsen HS, Hannibal J, Knudsen SM, Fahrenkrug J (2001) Pituitary adenylate cyclase-activating polypeptide induces Period1 and Period2 gene expression in the rat suprachiasmstic nucleus during late night. Neuroscience 103:433–441
Shioda S, Ohtaki H, Nakamachi T, Dohi K, Watanabe J, Nakajo S, Arata S, Kitamura S, Okuda H, Takenoya F, Kitamura Y (2006) Pleiotropic functions of PACAP in the CNS: neuroprotection and neurodevelopment. Ann N Y Acad Sci., 1070:550–60
Shivers BD, Gorce TJ, Gottschall, PE, Arimura, A (1991) Two high affinity binding sites for pituitary adenylate cyclase activating polypeptide have different tissue distribution. Endocrinology 128:3055–3065
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Arata, S., Hosono, T., Taketomi, Y., Kageyama, H., Nakamachi, T., Shioda, S. (2009). Increased behavioral activity with regular circadian rhythm in PACAP specific receptor (PAC1) transgenic mice. In: Shioda, S., Homma, I., Kato, N. (eds) Transmitters and Modulators in Health and Disease. Springer, Tokyo. https://doi.org/10.1007/978-4-431-99039-0_18
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DOI: https://doi.org/10.1007/978-4-431-99039-0_18
Publisher Name: Springer, Tokyo
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