Master of Science (MS), Wright State University, 2014, Physiology and Neuroscience

Transcranial direct current stimulation (tDCS) has been utilized in human studies to modulate a multitude of psychological, cognitive, and psychiatric disorders. There have been positive behavioral results in human subjects but our knowledge of biological processes occurring during stimulation to elicit behavioral outcomes is limited. Our study utilizes a rodent tDCS (R-tDCS) model in which Sprague Dawley rats receive tDCS in order to examine whether tDCS affects neuronal activation. We examined two immediate early genes (IEG's), cFos and zif268, in order to discern if tDCS affects neuronal activation. Our findings indicate that tDCS does affect neuronal activation by means of IEG induction and that there is dose dependence between current intensity used and mRNA levels of IEG's. These findings are important because they show biologically tDCS affecting neuronal activation. This study aided the scientific community in better understanding what is occurring biologically during tDCS.

Committee: Ryan Jankord Ph.D. (Advisor); Larry Ream Ph.D. (Committee Member); David Ladle Ph.D. (Committee Member) Subjects: Neurosciences

MS, Kent State University, 2009, College of Arts and Sciences / School of Biomedical Sciences

The suprachiasmatic nucleus of the hypothalamus (SCN) is the primary mammalian circadian clock. The SCN relies on photic cues to synchronize rhythms to the environment. Glutamate transmits photic information to the SCN and the non-competitive NMDA receptor antagonist MK-801 attenuates the expression of c-fos in the SCN of hamsters as well as the phase shifting effects of light in both hamsters and rats. The SCN subregions of the mouse are not as anatomically well defined as those of the hamster and rat. The goal of this study was to determine whether regional specificity of immediate-early gene expression in mice follows the same pattern as it does in hamsters and to establish a clearer picture of the pathways governing gene expression patterns in the SCN during the early and the late night. We performed an analysis of the effects of MK-801 administration on light-induced expression of the immediate early genes c-fos and egr1 as well as the MAP kinase activation indicator p-ERK in both the early and late night. MK-801 inhibited both c-fos and egr1 expression in the late night in the mouse SCN but had no effect on p-ERK expression. In hamsters, there was a near significant decrease in c-fos expression in the ventral 1/3 of the SCN which coincided with a significant decrease in c-fos expression in the ventral 1/3 of the mouse SCN. Egr1 expression was significantly decreased in the dorsal portion of the SCN in mice. MK-801 administration prior to a light pulse had no effect on the phase-delaying effect of a light pulse in the early night. These findings lead us to conclude that NMDA receptor activation in the dorsal areas of the SCN increases egr1 expression and receptor activation in the ventral areas of the SCN increases c-fos expression. However, c-fos attenuation in just the ventral portion of the SCN is not sufficient to cause a blockage of phase-shifting in the wheel running behavior of mice.

Committee: Dr. Eric Mintz PhD (Advisor); Dr. Heather Caldwell PhD (Committee Member); Dr. John Johnson PhD (Committee Member) Subjects: Neurology

PHD, Kent State University, 2007, College of Biomedical Sciences

Viral infection induces expression and activation of several genes involved directly or indirectly in antiviral defense. Protein kinase R (PKR), a Ser/Thr kinase induced by interferons and activated by double-stranded RNA (dsRNA) is a crucial component in mediating cellular antiviral action. Following activation by dsRNA, PKR initiates antiviral defense by inhibiting translation and inducing apoptosis. Apart from its role in translational inhibition, PKR has been implicated as a key integrator of many other signaling pathways stimulated by lipopolysaccharide, cytokines, growth factors and different types of cellular stresses. In order to define PKR dependent genes to better elucidate its physiological function, gene expression profiling following dsRNA treatment was performed on wild-type (wt) and PKR knockout (pkr-ko) spleen derived macrophage cell lines (SM) cells). The microarray results identified several novel PKR-dependent genes whose expression is induced by dsRNA treatment of mouse macrophages. The expression of early growth response-1 (Egr-1), an immediate early gene was highly induced in a PKR dependent manner on dsRNA treatment. NF-kB was determined to be a key component in regulation of the dsRNA mediated PKR-dependent, Egr-1 induction.Earlier reports have implied a role for PKR in induction and activation of AP-1 family members including c-Fos and ATF2 in response to different stimuli. A novel role for PKR in up-regulation of the AP-1 transcription factor c-Jun in response to dsRNA is documented in this thesis. Depending on the cell type, dsRNA mediated c-Jun induction is shown to be dependent on c-Jun NH2-terminal kinase JNK or extracellular signal related kinase ERK. Additionally, a role for c-AMP response element binding protein CREB is implicated in dsRNA mediated c-Jun induction. Importantly, activation of CREB, in response to dsRNA was impaired in the absence of PKR in SM cells.A role for PKR in the regulation of different pro-inflammatory cytokin (open full item for complete abstract)

Committee: Bryan Williams (Advisor) Subjects: Biology, Molecular