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kent1290535254.pdf (2.11 MB)
ETD Abstract Container
Abstract Header
Characterization of the Circadian Clock in Pet-1 Knockout Mice
Author Info
Gilbert, Erin V.
Permalink:
http://rave.ohiolink.edu/etdc/view?acc_num=kent1290535254
Abstract Details
Year and Degree
2010, PHD, Kent State University, College of Arts and Sciences / School of Biomedical Sciences.
Abstract
The suprachiasmatic nucleus (SCN) drives circadian rhythms of physiology and behavior and synchronizes the timing of circadian clocks in other tissues via unknown signals. One of the major input signals to the SCN is serotonin (5-HT), which is thought to communicate information about behavioral activity to the circadian clock. In mice lacking the transcription factor Pet-1 the 5-HT system fails to develop normally, resulting in mice with only a small fraction of their normal complement of 5-HT neurons. Pet-1 knockout mice show longer endogenous circadian periods indicating that 5-HT may function as an overall phase advancing signal to the clock. The loss of the advancing signal also causes a shift in peak wheel running activity from early to late night and a phase response curve to light which is reduced in amplitude when compared to wildtype leading to smaller phase delays in Pet-1 knockout animals. No alterations in response to pharmacological nonphotic stimuli (8-OH-DPAT) were seen and responses to non-pharmacological, nonphotic stimuli suggest that cage changes are a more significant stimulus for female animals. Within the cerebellum, a site of an extra-SCN oscillator, Pet-1 knockout animals show attenuation of Per1 expression 4 hours before lights off and generally attenuated levels of Per2 expression. The lack of 5-HT did not affect expression of the core clock genes Clock, Npas2, Bmal1, or the immediate early gene Fos indicating that 5-HT may play a role in modulating levels of Per gene expression. However, Fos expression in response to injection of 8-OH-DPAT was increased in wildtype but not Pet-1 knockout animals which suggests the possibility that 5-HT receptors in knockout mice are unable to respond to drugs which affect the 5-HT system. Together, these data suggest that a developmental deficit of the serotonergic system may alter the circadian clock in a way that differs from current understanding of the system and add to our knowledge of the role of 5-HT in circadian rhythm generation.
Committee
Eric Mintz, PhD (Committee Chair)
Sean Veney, PhD (Committee Member)
Heather Caldwell, PhD (Committee Member)
Gail Fraizer, PhD (Committee Member)
Amy Milsted, PhD (Committee Member)
Pages
162 p.
Subject Headings
Neurobiology
;
Neurosciences
Keywords
Pet-1
;
serotonin
;
circadian
;
suprachiasmatic
;
clock genes
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Citations
Gilbert, E. V. (2010).
Characterization of the Circadian Clock in Pet-1 Knockout Mice
[Doctoral dissertation, Kent State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=kent1290535254
APA Style (7th edition)
Gilbert, Erin.
Characterization of the Circadian Clock in Pet-1 Knockout Mice.
2010. Kent State University, Doctoral dissertation.
OhioLINK Electronic Theses and Dissertations Center
, http://rave.ohiolink.edu/etdc/view?acc_num=kent1290535254.
MLA Style (8th edition)
Gilbert, Erin. "Characterization of the Circadian Clock in Pet-1 Knockout Mice." Doctoral dissertation, Kent State University, 2010. http://rave.ohiolink.edu/etdc/view?acc_num=kent1290535254
Chicago Manual of Style (17th edition)
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Document number:
kent1290535254
Download Count:
646
Copyright Info
© 2010, all rights reserved.
This open access ETD is published by Kent State University and OhioLINK.