Bruce F. O'Hara - US grants
Affiliations: | University of Kentucky, Lexington, KY |
Area:
Sleep and circadian rhythmsWebsite:
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The funding information displayed below comes from the NIH Research Portfolio Online Reporting Tools and the NSF Award Database.The grant data on this page is limited to grants awarded in the United States and is thus partial. It can nonetheless be used to understand how funding patterns influence mentorship networks and vice-versa, which has deep implications on how research is done.
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High-probability grants
According to our matching algorithm, Bruce F. O'Hara is the likely recipient of the following grants.| Years | Recipients | Code | Title / Keywords | Matching score |
|---|---|---|---|---|
| 1994 — 1998 | O'hara, Bruce F | K21Activity Code Description: To foster the development of outstanding scientists with potential for making important contributions to the fields of alcoholism, drug abuse or mental health (ADM) research. Primarily intended to meet the need for supervised research experience for highly promising biological or behavioral scientists who need further supervised research experience. |
Molecular Approaches to Drugs of Abuse and Arousal State @ Stanford University The proposal is focused primarily on the effects of nicotine in the suprachiasmatic nucleus (SCN), locus of the circadian clock in mammals, and an important influence on arousal state control. Preliminary studies have shown that nicotine produces robust phase shifts of the circadian clock in vitro. This effect on the clock will be explored using a rodent model to determine the mechanisms of nicotine induced phase shifts and whether nicotine can entrain circadian rhythms both in vivo and in vitro. The clock resetting properties of nicotine need to be taken into account to fully understand the addictive characteristics of cigarette smoking. The pharmacological nature of the receptors at which nicotine exerts its effects in the SCN will be determined, as well as the intracellular mechanisms mediating the response. Particular attention will be paid to the alpha7 nicotinic acetylcholine receptor (nAChR) subunit, which is the only alpha subunit found within the SCN. This newly cloned subunit produces a novel nAChR with unique pharmacology, including high affinity for alpha-bungarotoxin (alpha-BTX) when expressed in oocytes. This work will be done primarily in the in vitro SCN slice preparation, which maintains a circadian rhythm of neuronal firing. This rhythm is strongly altered by the application of nicotine, providing an ideal System in which to examine the details of nicotine action. The effects of nicotine on the biological clock in whole animals will be examined in an automated system known as SCORE, which can measure locomotor activity, drinking, feeding, body temperature, EEG and other variables simultaneously from many animals. The ability of nicotine to entrain circadian rhythms in rats could have relevance to human addiction. Part of the addictive liability of nicotine may result from a kind of circadian self-medication in smokers, especially to augment arousal in the morning. Smoking may actually synchronize the rest-activity cycle in a fashion similar and perhaps complementary to that of light. Nicotine withdrawal, on the other hand, might result in the loss of such synchronization and concomitant difficulty in arousing at preferred clock times, surely an aversive consequence in a clock-conscious society. Furthermore, the smoker in withdrawal might be most prone to recidivism early in the morning. The final specific aim of this proposal examines the effect of nicotine on the fetal SCN. A recent report has shown that cocaine administration in pregnant rats causes a specific induction of c-fos in the fetal SCN, raising the possibility of deleterious effects on the developing biological clock. Preliminary evidence presented here suggests that nicotine has a similar effect. In both cases, the response occurs in the fetus but not in adults. This proposal will examine the developmental changes in this response for both nicotine and cocaine, and investigate possible explanations for this unexpected finding. |
0.954 |
| 2010 — 2011 | Hamre, Kristin M O'hara, Bruce F |
R21Activity Code Description: To encourage the development of new research activities in categorical program areas. (Support generally is restricted in level of support and in time.) |
Gender and Genetic Effects On Sleep:Wake Parameters Following Ethanol Exposure @ University of Tennessee Health Sci Ctr DESCRIPTION (provided by applicant): Withdrawal from chronic ethanol exposure results in a number of physiological responses. Two of those responses are altered sleep parameters and increased anxiety. However, little is known about either the factors that influence the severity of the alterations in sleep parameters or about whether there is a relationship between sleep: wake characteristics and anxiety during ethanol withdrawal. Two factors that have been shown to affect both sleep: wake characteristics and the severity of ethanol's withdrawal effects are the genetics or gender of the organism, and thus, the first experiment will test the hypotheses that genetics and/or gender or a combination of the two variables influences the severity of ethanol-induced changes in sleep. Testing of these hypotheses will be facilitated by the use of a novel system, the Piezo system, developed by the PI Dr. O'Hara. This system has the advantage of evaluating sleep patterns in a non-invasive fashion that also requires minimal labor investment. To test these hypotheses, DBA/2J (D2) and C57BL/6J (B6) mice as well as the BXD recombinant inbred mice generated by intercrossing the D2 and B6 mice will be examined. The addition of the BXD strains will allow us to not only address the hypotheses, but also to identify the region(s) of the genome that mediate any differential responses. Ethanol exposure will be given using vapor inhalation and following the multiple cycles of withdrawal and exposure of Veatch (2006), a technique that allows for the rapid induction of alcohol dependence. Comparisons of the sleep: wake parameters before ethanol exposure (baseline) will be compared to those during withdrawal. The second experiment will examine whether there is a relationship between the anxiety phenotypes of the animal and the severity of sleep alterations during ethanol withdrawal to determine whether the mice with the highest level of anxiety also show the most severe sleep disruptions during withdrawal. The anxiety phenotype of the mice will be addressed using several different behavioral paradigms including the elevated plus maze and locomotor activity in an activity chamber. Mice will be exposed to ethanol and the sleep: wake parameters monitored in the same manner as in the first experiment. Anxiety phenotypes will be assessed prior to ethanol exposure and during withdrawal. These experiments will provide insights into variables that need to be considered in the design of treatment programs for particular patients or in understanding the factors that mediate differences in treatment outcomes. PUBLIC HEALTH RELEVANCE: Sleep disruptions are one of the physiological responses that occur during alcohol withdrawal and have been shown to be a negative predictor of success in alcohol withdrawal. This proposal will provide insight into the role of gender and genetics in sleep disruptions following alcohol exposure and withdrawal as well as identify regions of the genome that underlie these differences. |
0.961 |
| 2011 — 2012 | Lifshitz, Jonathan [⬀] O'hara, Bruce F |
R21Activity Code Description: To encourage the development of new research activities in categorical program areas. (Support generally is restricted in level of support and in time.) |
Post Traumatic Sleep: An Individualized Indicator of Severity and Recovery @ University of Kentucky DESCRIPTION (provided by applicant): The purpose of sleep continues to be debated. Prevailing hypotheses suggest a role in restoring energy balance, permitting synaptic reorganization, or cellular repair. With a traumatic brain injury, the mechanical forces and ensuing cellular signaling disrupt energy balance, initiate synaptic deafferentation followed by plasticity, and damage membranes, proteins and structural elements. Thus, acute post-traumatic sleep may mitigate injury-related damage. However, for the more than 1.4 million concussed individuals per year in the United States, prevailing folklore recommends that they should not be allowed to sleep or be awoken regularly, which is unsupported by medical evidence. Moreover, this sleep disturbance counteracts the natural repair processes of sleep that would be promoted by the ubiquitous inflammatory response after brain injury, as occurs with cytokine signaling upon infection. Surprisingly, the utility or detriment of acute post-traumatic sleep has yet to be explored. The current proposal tests the hypothesis that sleep is an immediate natural response to diffuse brain injury likely promoting recovery of the injured brain. Aim 1 will correlate quantitative sleep parameters acutely following mild and moderate diffuse brain injury in the mouse to chronic physiological, behavioral and histopathological outcomes. Aim 2 will explore the consequences of sleep disturbance on cognitive function, cytokine and glucocorticoid levels and histopathology across limbic and sleep structures. Post- traumatic sleep will be monitored by novel non-invasive technology validated for sleep- wake studies. This system employs custom-designed pressure sensors on the cage floor that continuously monitor for the motion associated with rhythmic breathing while animals are in a sleep posture. These experiments examine, for the first time, the effects of diffuse brain injury on sleep-wake patterns. Post-traumatic interventions to disrupt sleep may worsen or mitigate the behavioral and histopathological consequences of injury. Post-traumatic sleep may come to serve as an individualized biomarker to measure the severity of the initial injury and monitor the recovery process. For mild TBI, sleep itself could become a plausible behavioral intervention to mitigate the enduring neurological consequences of TBI. PUBLIC HEALTH RELEVANCE: After a concussion, prevailing folklore recommends that individuals should not be allowed to sleep or be awoken regularly. Since sleep may be responsible for cellular repair and reorganization, post-injury sleep disturbance may delay or even prevent recovery. This proposal evaluates post-injury sleep in a mouse model of traumatic brain injury and the consequences, good or bad, of disturbing sleep shortly after injury. |
1 |
| 2020 — 2021 | Bachstetter, Adam D (co-PI) [⬀] Duncan, Marilyn J. Murphy, Michael Paul [⬀] Murphy, Michael Paul [⬀] Murphy, Michael Paul [⬀] O'hara, Bruce F Sunderam, Sridhar |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Sleep Fragmentation and Alzheimer?S Disease @ University of Kentucky Chronic sleep disruption, resulting from work schedules, noise exposure, family obligations, sleep disorders, or lifestyle choices, is a pervasive feature of contemporary life. Sleep problems affect up to 40% of AD patients, may precede cognitive impairments by more than a decade, and worsen as the disease progresses. As well as affecting mood and well-being, sleep disruption may drive the development of AD neuropathology for instance, by reducing clearance of amyloid-? (A?) and by promoting a neurotoxic proinflammatory state involving astrocytes and microglia. Sleep disruption can include reduced total sleep (sleep restriction [SR]), loss of deep sleep (also known as slow-wave sleep [SWS], marked by large amplitude, low frequency electrical activity), and fragmentation of sleep (SF) into shorter bouts. Fragmentation of the daily sleep-wake rhythm is associated with greater risk of incident AD and earlier cognitive decline in older humans. In spite of these correlative studies, whether or how chronic SF impacts the progression of AD has not been experimentally investigated. SF may be a better model of the sleep disruption associated with AD than the traditional approach of SR. Our studies of AD mouse models show that spontaneously occurring SF is associated with more severe A? accumulation and that experimentally-induced SF leads to A? accumulation and neuroinflammation. Besides SF, loss of SWS may exacerbate AD, and improving SWS may be beneficial in mild cognitive impairment (MCI) or even in AD. Since sleep disruption adversely affects the development of AD-related neuropathology, it is surprising that sleep enhancement (SE) strategies to consolidate sleep and increase SWS have not been adequately explored to slow or reverse these effects. Our overall working hypothesis is that a change in the quality of sleep, especially sleep fragmentation and loss of SWS, is more important than the quantity of sleep. Further, we hypothesize that the mechanism underlying these effects is primarily neuroinflammation, at least in part mediated by A? peptide deposition. We will use a unique, well-characterized mouse model, that exhibits AD-related A? pathology, neuroinflammation, and cognitive deficits. This project has three specific aims: (1) that SF will accelerate (and SE decelerate) AD progression; (2) that increases in A? accumulation mediates SF-induced neuroinflammation, neuropathology, and cognitive decline; and (3) that increases in neuroinflammation mediate SF-induced neuropathology and cognitive decline. We will use multiple novel approaches, including thermoneutral temperature manipulation, and a unique anti-inflammatory compound that has recently entered early stage clinical trials. Thus, these studies will elucidate the underlying mechanisms by which sleep disruption is linked to AD and will lay the groundwork for new therapeutic strategies. |
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