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Papers by Paulien Barf
was as good as in days without skipped sessions (Figure 1C, lenged in a symmetric three-arm maze ... more was as good as in days without skipped sessions (Figure 1C, lenged in a symmetric three-arm maze with a balanced approach of a positive reinforcer (food gathered at the end of the arm) and a negative reinforcer (a mild but aversive foot-shock; delivered via a grid floor at the end of the arm; Figure 1A; performanceR 80%; Wilcoxon signed rank test p> 0.80), rul-ing out the use of such timers. Second, to further test whether an interval timer could have been used, with the transition of lights on and/or off as a starting point under 12 hr:12 hr LD con-ditions, we tested time-place learning under constant-light conditions (Figure 1D). Mice performed equally well under constant-light and LD conditions (Wilcoxon signed rank test p> 0.43), rendering it unlikely that an interval timer was
Copyright © 2010 R. Paulien Barf et al. This is an open access article distributed under the Crea... more Copyright © 2010 R. Paulien Barf et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Epidemiological studies have shown an association between short or disrupted sleep and an increased risk for metabolic disorders. To assess a possible causal relationship, we examined the effects of experimental sleep disturbance on glucose regulation in Wistar rats under controlled laboratory conditions. Three groups of animals were used: a sleep restriction group (RS), a group subjected to moderate sleep disturbance without restriction of sleep time (DS), and a home cage control group. To establish changes in glucose regulation, animals were subjected to intravenous glucose tolerance tests (IVGTTs) before and after 1 or 8 days of sleep restriction or disturbance. Data show that both RS and DS reduce body weight without affecting f...
Background: Neuroinflammation is an important secondary mechanism that is a key mediator of the l... more Background: Neuroinflammation is an important secondary mechanism that is a key mediator of the long-term consequences of neuronal injury that occur in traumatic brain injury (TBI). Microglia are highly plastic cells with dual roles in neuronal injury and recovery. Recent studies suggest that the chemokine fractalkine (CX3CL1, FKN) mediates neural/microglial interactions via its sole receptor CX3CR1. CX3CL1/CX3CR1 signaling modulates microglia activation, and depending upon the type and time of injury, either protects or exacerbates neurological diseases. Methods: In this study, mice deficient in CX3CR1 were subjected to mild controlled cortical impact injury (CCI), a model of TBI. We evaluated the effects of genetic deletion of CX3CR1 on histopathology, cell death/survival, microglia activation, and cognitive function for 30 days post-injury. Results: During the acute post-injury period (24 h–15 days), motor deficits, cell death, and neuronal cell loss were more profound in injured...
There are large individual differences in the success rates of exercise intervention programs aim... more There are large individual differences in the success rates of exercise intervention programs aimed at the prevention and treatment of obesity-related disorders. In the present study, we tested the hypothesis that differences in coping style may impact the success rates of these intervention programs. We tested insulin responses before and after voluntary wheel running in both passive (insulin resistant) Roman Low Avoidance (RLA) and proactive (insulin sensitive) Roman High Avoidance (RHA) rats using intravenous glucose tolerance tests (IVGTTs). To control for a potential difference between voluntary and forced exercise, we also included RLA and RHA rats that were subjected to forced running. We found the following: 1) when given the opportunity to run voluntarily in a running wheel, passive RLA rats run more than proactively than RHA rats; 2) voluntary exercise leads to a normalization of insulin responses during an IVGTTs in RLA rats; and 3) there were no behavioral and physiological differences in efficacy between voluntary and forced running. We conclude that exercise, both forced and voluntary, is a successful lifestyle intervention for the treatment of hyperinsulinemia, especially in individuals with a passive coping style.
Psychoneuroendocrinology, 2016
Poor sleep quality or quantity impairs glycemic control and increases risk of disease under chron... more Poor sleep quality or quantity impairs glycemic control and increases risk of disease under chronic conditions. Recovery sleep may offset adverse metabolic outcomes of accumulated sleep debt, but the extent to which this occurs is unclear. We examined whether recovery sleep improves glucose metabolism in mice subjected to prolonged sleep disruption, and whether high-fat intake during sleep disruption exacerbates glycemic control. Adult male C57BL/6J mice were subjected to 18-h sleep fragmentation daily for 9 days, followed by 1 day of recovery. During sleep disruption, one group of mice was fed a high-fat diet (HFD) while another group was fed standard laboratory chow. Insulin sensitivity and glucose tolerance were assessed by insulin and glucose tolerance testing at baseline, after 3 and 7 days of sleep disruption, and at the end of the protocol after 24 h of undisturbed sleep opportunity (recovery). To characterize changes in sleep architecture that are associated with sleep debt and recovery, we quantified electroencephalogram (EEG) recordings during sleep fragmentation and recovery periods from an additional group of mice. We now report that 9 days of 18-h daily sleep fragmentation significantly reduces rapid eye movement sleep (REMS) and non-rapid eye movement sleep (NREMS). Mice respond with increases in REMS, but not NREMS, during the daily 6-h undisturbed sleep opportunity. However, both REMS and NREMS increase significantly during the 24-h recovery period. Although sleep disruption alone has no effect in this protocol, high fat feeding in combination with sleep disruption impairs glucose tolerance, effects that are reversed by recovery sleep. Insulin sensitivity modestly improves after 3 days of sleep fragmentation and after 24 h of recovery, with significantly greater improvements in mice exposed to HFD during sleep disruption. Improvements in both glucose tolerance and insulin sensitivity are associated with NREMS rebound, raising the possibility that this sleep phase contributes to restorative effects of recovery sleep on glycemic control.
Journal of Neuroinflammation, 2015
Background: Neuroinflammation is an important secondary mechanism that is a key mediator of the l... more Background: Neuroinflammation is an important secondary mechanism that is a key mediator of the long-term consequences of neuronal injury that occur in traumatic brain injury (TBI). Microglia are highly plastic cells with dual roles in neuronal injury and recovery. Recent studies suggest that the chemokine fractalkine (CX3CL1, FKN) mediates neural/microglial interactions via its sole receptor CX3CR1. CX3CL1/CX3CR1 signaling modulates microglia activation, and depending upon the type and time of injury, either protects or exacerbates neurological diseases. Methods: In this study, mice deficient in CX3CR1 were subjected to mild controlled cortical impact injury (CCI), a model of TBI. We evaluated the effects of genetic deletion of CX3CR1 on histopathology, cell death/survival, microglia activation, and cognitive function for 30 days post-injury. Results: During the acute post-injury period (24 h-15 days), motor deficits, cell death, and neuronal cell loss were more profound in injured wild-type than in CX3CR1 −/− mice. In contrast, during the chronic period of 30 days post-TBI, injured CX3CR1 −/− mice exhibited greater cognitive dysfunction and increased neuronal death than wild-type mice. The protective and deleterious effects of CX3CR1 were associated with changes in microglia phenotypes; during the acute phase CX3CR1 −/− mice showed a predominant anti-inflammatory M2 microglial response, with increased expression of Ym1, CD206, and TGFβ. In contrast, increased M1 phenotypic microglia markers, Marco, and CD68 were predominant at 30 days post-TBI. Conclusion: Collectively, these novel data demonstrate a time-dependent role for CX3CL1/CX3CR1 signaling after TBI and suggest that the acute and chronic responses to mild TBI are modulated in part by distinct microglia phenotypes.
Physiology & Behavior, 2012
Sleep disturbances, induced by either lifestyle, shift work or sleeping disorders, have become mo... more Sleep disturbances, induced by either lifestyle, shift work or sleeping disorders, have become more prevalent in our 24/7 Western society. Sleep disturbances are associated with impaired health including metabolic diseases such as obesity and type 2 diabetes. The question remains whether there is a direct effect of disturbed sleep on glucose homeostasis. Experimental studies under controlled laboratory conditions in both humans and experimental animals revealed that there are differences between the effects of acute or chronic sleep disturbance. Acute sleep restriction clearly leads to glucose intolerance, often combined with insulin resistance. Although glucose intolerance does also occur after chronic sleep disturbance, the changes in insulin can vary, dependent on the body weight changes in the various studies. The underlying mechanism that might cause the changes in glucose homeostasis after sleep disturbance remains unclear, but both the biological clock located in the nucleus ...
International Journal of Endocrinology, 2010
Epidemiological studies have shown an association between short or disrupted sleep and an increas... more Epidemiological studies have shown an association between short or disrupted sleep and an increased risk for metabolic disorders. To assess a possible causal relationship, we examined the effects of experimental sleep disturbance on glucose regulation in Wistar rats under controlled laboratory conditions. Three groups of animals were used: a sleep restriction group (RS), a group subjected to moderate sleep disturbance without restriction of sleep time (DS), and a home cage control group. To establish changes in glucose regulation, animals were subjected to intravenous glucose tolerance tests (IVGTTs) before and after 1 or 8 days of sleep restriction or disturbance. Data show that both RS and DS reduce body weight without affecting food intake and also lead to hyperglycemia and decreased insulin levels during an IVGTT. Acute sleep disturbance also caused hyperglycemia during an IVGTT, yet, without affecting the insulin response. In conclusion, both moderate and severe disturbances of sleep markedly affect glucose homeostasis and body weight control.
SLEEP, 2000
Sleep Homeostasis in the Day-Active Tree Shrew-Coolen et al Sleep in humans and other mammalian s... more Sleep Homeostasis in the Day-Active Tree Shrew-Coolen et al Sleep in humans and other mammalian species is a complex phenomenon consisting of 2 distinct stages, nonrapid eye movement (NREM) and rapid eye movement (REM) sleep. Each of these 2 stages may have its own function in brain recovery and information processing. However, despite many theories, these functions are still largely unknown. It is generally accepted that a need for sleep builds up during wakefulness. This notion is supported by the finding that extended wakefulness or sleep deprivation (SD) is associated with an increased drive for sleep and is followed by compensatory rebound sleep. This is particularly true for NREM sleep, which may display a compensatory increase in both time and intensity. The NREM sleep intensity is reflected in the amount of slow waves in the EEG. 6-9 EEG slow-wave activity at the start of NREM sleep, i.e., the spectral power in the 1-4 Hz range, is a clear function of the duration of prior wakefulness. 10-13 SWA is highest at the beginning of sleep and gradually declines during the course of the sleep phase as the NREM sleep debt dissipates. Also REM sleep often displays a rebound increase after SD. It is still generally believed that REM sleep recovery
Journal of Sleep Research, 2011
have shown that brief SD immediately following a mild foot shock impairs consolidation of context... more have shown that brief SD immediately following a mild foot shock impairs consolidation of contextual fear memory as reflected in a reduced behavioral freezing response during re-exposure to the shock context later on. In the first part of this study, we examined whether this reduced freezing response is accompanied by an attenuated fear-induced activation of the hypothalamic-pituitary-adrenal (HPA) axis. Results show that 6 hours of SD immediately following the initial shock results in a diminished adrenal corticosterone (CORT) response upon re-exposure to the shock context the next day. In the second part, we established whether the attenuated freezing response in SD animals is associated with reduced activation of relevant brain areas known to be involved in the retrieval and expression of fear memory. Immunohistochemical analysis of brain slices showed that the normal increase in phosphorylation of the transcription factor cAMP response-element binding protein (CREB) upon reexposure to the shock context was reduced in SD animals in the CA1 region of the hippocampus and in the amygdala. In conclusion, brief SD impairs the consolidation of contextual fear memory. Upon reexposure to the context, this is reflected in a diminished behavioral freezing response, an attenuated HPA axis response, and a reduction of the normal increase of phosphorylated CREB (pCREB) expression in hippocampus and amygdala.
Journal of Neuroscience Methods, 2013
• The method used is effective in fragmenting sleep of mice for prolonged periods without behavio... more • The method used is effective in fragmenting sleep of mice for prolonged periods without behavioral adaptation.
Hormones and Behavior, 2012
There are large individual differences in the success rates of exercise intervention programs aim... more There are large individual differences in the success rates of exercise intervention programs aimed at the prevention and treatment of obesity-related disorders. In the present study, we tested the hypothesis that differences in coping style may impact the success rates of these intervention programs. We tested insulin responses before and after voluntary wheel running in both passive (insulin resistant) Roman Low Avoidance (RLA) and proactive (insulin sensitive) Roman High Avoidance (RHA) rats using intravenous glucose tolerance tests (IVGTTs). To control for a potential difference between voluntary and forced exercise, we also included RLA and RHA rats that were subjected to forced running. We found the following: 1) when given the opportunity to run voluntarily in a running wheel, passive RLA rats run more than proactively than RHA rats; 2) voluntary exercise leads to a normalization of insulin responses during an IVGTTs in RLA rats; and 3) there were no behavioral and physiological differences in efficacy between voluntary and forced running. We conclude that exercise, both forced and voluntary, is a successful lifestyle intervention for the treatment of hyperinsulinemia, especially in individuals with a passive coping style.
Current Biology, 2008
Endogenous biological clocks allow organisms to anticipate daily environmental cycles . The abili... more Endogenous biological clocks allow organisms to anticipate daily environmental cycles . The ability to achieve timeplace associations is key to the survival and reproductive success of animals. The ability to link the location of a stimulus (usually food) with time of day has been coined timeplace learning , but its circadian nature was only shown in honeybees [1] and birds . So far, an unambiguous circadian time-place-learning paradigm for mammals is lacking. We studied whether expression of the clock gene Cryptochrome (Cry), crucial for circadian timing, is a prerequisite for time-place learning. Time-place learning in mice was achieved by developing a novel paradigm in which food reward at specific times of day was counterbalanced by the penalty of receiving a mild footshock. Mice lacking the core clock genes Cry1 and Cry2 (Cry double knockout mice; Cry1 2/2 Cry2 2/2 ) learned to avoid unpleasant sensory experiences (mild footshock) and could locate a food reward in a spatial learning task (place preference). These mice failed, however, to learn time-place associations. This specific learning and memory deficit shows that a Cry-gene dependent circadian timing system underlies the utilization of time of day information. These results reveal a new functional role of the mammalian circadian timing system.
AJP: Regulatory, Integrative and Comparative Physiology, 2012
Physiology & Behavior, 2012
► The slowly rotating drum method effectively restricted sleep time in rats. ► Short sleep increa... more ► The slowly rotating drum method effectively restricted sleep time in rats. ► Short sleep increases energy expenditure but no change in food intake. ► Short sleep attenuates weight gain in rats. ► Plasma glucose, insulin and leptin levels were reduced, reflecting the nutritional status.
was as good as in days without skipped sessions (Figure 1C, lenged in a symmetric three-arm maze ... more was as good as in days without skipped sessions (Figure 1C, lenged in a symmetric three-arm maze with a balanced approach of a positive reinforcer (food gathered at the end of the arm) and a negative reinforcer (a mild but aversive foot-shock; delivered via a grid floor at the end of the arm; Figure 1A; performanceR 80%; Wilcoxon signed rank test p> 0.80), rul-ing out the use of such timers. Second, to further test whether an interval timer could have been used, with the transition of lights on and/or off as a starting point under 12 hr:12 hr LD con-ditions, we tested time-place learning under constant-light conditions (Figure 1D). Mice performed equally well under constant-light and LD conditions (Wilcoxon signed rank test p> 0.43), rendering it unlikely that an interval timer was
Copyright © 2010 R. Paulien Barf et al. This is an open access article distributed under the Crea... more Copyright © 2010 R. Paulien Barf et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Epidemiological studies have shown an association between short or disrupted sleep and an increased risk for metabolic disorders. To assess a possible causal relationship, we examined the effects of experimental sleep disturbance on glucose regulation in Wistar rats under controlled laboratory conditions. Three groups of animals were used: a sleep restriction group (RS), a group subjected to moderate sleep disturbance without restriction of sleep time (DS), and a home cage control group. To establish changes in glucose regulation, animals were subjected to intravenous glucose tolerance tests (IVGTTs) before and after 1 or 8 days of sleep restriction or disturbance. Data show that both RS and DS reduce body weight without affecting f...
Background: Neuroinflammation is an important secondary mechanism that is a key mediator of the l... more Background: Neuroinflammation is an important secondary mechanism that is a key mediator of the long-term consequences of neuronal injury that occur in traumatic brain injury (TBI). Microglia are highly plastic cells with dual roles in neuronal injury and recovery. Recent studies suggest that the chemokine fractalkine (CX3CL1, FKN) mediates neural/microglial interactions via its sole receptor CX3CR1. CX3CL1/CX3CR1 signaling modulates microglia activation, and depending upon the type and time of injury, either protects or exacerbates neurological diseases. Methods: In this study, mice deficient in CX3CR1 were subjected to mild controlled cortical impact injury (CCI), a model of TBI. We evaluated the effects of genetic deletion of CX3CR1 on histopathology, cell death/survival, microglia activation, and cognitive function for 30 days post-injury. Results: During the acute post-injury period (24 h–15 days), motor deficits, cell death, and neuronal cell loss were more profound in injured...
There are large individual differences in the success rates of exercise intervention programs aim... more There are large individual differences in the success rates of exercise intervention programs aimed at the prevention and treatment of obesity-related disorders. In the present study, we tested the hypothesis that differences in coping style may impact the success rates of these intervention programs. We tested insulin responses before and after voluntary wheel running in both passive (insulin resistant) Roman Low Avoidance (RLA) and proactive (insulin sensitive) Roman High Avoidance (RHA) rats using intravenous glucose tolerance tests (IVGTTs). To control for a potential difference between voluntary and forced exercise, we also included RLA and RHA rats that were subjected to forced running. We found the following: 1) when given the opportunity to run voluntarily in a running wheel, passive RLA rats run more than proactively than RHA rats; 2) voluntary exercise leads to a normalization of insulin responses during an IVGTTs in RLA rats; and 3) there were no behavioral and physiological differences in efficacy between voluntary and forced running. We conclude that exercise, both forced and voluntary, is a successful lifestyle intervention for the treatment of hyperinsulinemia, especially in individuals with a passive coping style.
Psychoneuroendocrinology, 2016
Poor sleep quality or quantity impairs glycemic control and increases risk of disease under chron... more Poor sleep quality or quantity impairs glycemic control and increases risk of disease under chronic conditions. Recovery sleep may offset adverse metabolic outcomes of accumulated sleep debt, but the extent to which this occurs is unclear. We examined whether recovery sleep improves glucose metabolism in mice subjected to prolonged sleep disruption, and whether high-fat intake during sleep disruption exacerbates glycemic control. Adult male C57BL/6J mice were subjected to 18-h sleep fragmentation daily for 9 days, followed by 1 day of recovery. During sleep disruption, one group of mice was fed a high-fat diet (HFD) while another group was fed standard laboratory chow. Insulin sensitivity and glucose tolerance were assessed by insulin and glucose tolerance testing at baseline, after 3 and 7 days of sleep disruption, and at the end of the protocol after 24 h of undisturbed sleep opportunity (recovery). To characterize changes in sleep architecture that are associated with sleep debt and recovery, we quantified electroencephalogram (EEG) recordings during sleep fragmentation and recovery periods from an additional group of mice. We now report that 9 days of 18-h daily sleep fragmentation significantly reduces rapid eye movement sleep (REMS) and non-rapid eye movement sleep (NREMS). Mice respond with increases in REMS, but not NREMS, during the daily 6-h undisturbed sleep opportunity. However, both REMS and NREMS increase significantly during the 24-h recovery period. Although sleep disruption alone has no effect in this protocol, high fat feeding in combination with sleep disruption impairs glucose tolerance, effects that are reversed by recovery sleep. Insulin sensitivity modestly improves after 3 days of sleep fragmentation and after 24 h of recovery, with significantly greater improvements in mice exposed to HFD during sleep disruption. Improvements in both glucose tolerance and insulin sensitivity are associated with NREMS rebound, raising the possibility that this sleep phase contributes to restorative effects of recovery sleep on glycemic control.
Journal of Neuroinflammation, 2015
Background: Neuroinflammation is an important secondary mechanism that is a key mediator of the l... more Background: Neuroinflammation is an important secondary mechanism that is a key mediator of the long-term consequences of neuronal injury that occur in traumatic brain injury (TBI). Microglia are highly plastic cells with dual roles in neuronal injury and recovery. Recent studies suggest that the chemokine fractalkine (CX3CL1, FKN) mediates neural/microglial interactions via its sole receptor CX3CR1. CX3CL1/CX3CR1 signaling modulates microglia activation, and depending upon the type and time of injury, either protects or exacerbates neurological diseases. Methods: In this study, mice deficient in CX3CR1 were subjected to mild controlled cortical impact injury (CCI), a model of TBI. We evaluated the effects of genetic deletion of CX3CR1 on histopathology, cell death/survival, microglia activation, and cognitive function for 30 days post-injury. Results: During the acute post-injury period (24 h-15 days), motor deficits, cell death, and neuronal cell loss were more profound in injured wild-type than in CX3CR1 −/− mice. In contrast, during the chronic period of 30 days post-TBI, injured CX3CR1 −/− mice exhibited greater cognitive dysfunction and increased neuronal death than wild-type mice. The protective and deleterious effects of CX3CR1 were associated with changes in microglia phenotypes; during the acute phase CX3CR1 −/− mice showed a predominant anti-inflammatory M2 microglial response, with increased expression of Ym1, CD206, and TGFβ. In contrast, increased M1 phenotypic microglia markers, Marco, and CD68 were predominant at 30 days post-TBI. Conclusion: Collectively, these novel data demonstrate a time-dependent role for CX3CL1/CX3CR1 signaling after TBI and suggest that the acute and chronic responses to mild TBI are modulated in part by distinct microglia phenotypes.
Physiology & Behavior, 2012
Sleep disturbances, induced by either lifestyle, shift work or sleeping disorders, have become mo... more Sleep disturbances, induced by either lifestyle, shift work or sleeping disorders, have become more prevalent in our 24/7 Western society. Sleep disturbances are associated with impaired health including metabolic diseases such as obesity and type 2 diabetes. The question remains whether there is a direct effect of disturbed sleep on glucose homeostasis. Experimental studies under controlled laboratory conditions in both humans and experimental animals revealed that there are differences between the effects of acute or chronic sleep disturbance. Acute sleep restriction clearly leads to glucose intolerance, often combined with insulin resistance. Although glucose intolerance does also occur after chronic sleep disturbance, the changes in insulin can vary, dependent on the body weight changes in the various studies. The underlying mechanism that might cause the changes in glucose homeostasis after sleep disturbance remains unclear, but both the biological clock located in the nucleus ...
International Journal of Endocrinology, 2010
Epidemiological studies have shown an association between short or disrupted sleep and an increas... more Epidemiological studies have shown an association between short or disrupted sleep and an increased risk for metabolic disorders. To assess a possible causal relationship, we examined the effects of experimental sleep disturbance on glucose regulation in Wistar rats under controlled laboratory conditions. Three groups of animals were used: a sleep restriction group (RS), a group subjected to moderate sleep disturbance without restriction of sleep time (DS), and a home cage control group. To establish changes in glucose regulation, animals were subjected to intravenous glucose tolerance tests (IVGTTs) before and after 1 or 8 days of sleep restriction or disturbance. Data show that both RS and DS reduce body weight without affecting food intake and also lead to hyperglycemia and decreased insulin levels during an IVGTT. Acute sleep disturbance also caused hyperglycemia during an IVGTT, yet, without affecting the insulin response. In conclusion, both moderate and severe disturbances of sleep markedly affect glucose homeostasis and body weight control.
SLEEP, 2000
Sleep Homeostasis in the Day-Active Tree Shrew-Coolen et al Sleep in humans and other mammalian s... more Sleep Homeostasis in the Day-Active Tree Shrew-Coolen et al Sleep in humans and other mammalian species is a complex phenomenon consisting of 2 distinct stages, nonrapid eye movement (NREM) and rapid eye movement (REM) sleep. Each of these 2 stages may have its own function in brain recovery and information processing. However, despite many theories, these functions are still largely unknown. It is generally accepted that a need for sleep builds up during wakefulness. This notion is supported by the finding that extended wakefulness or sleep deprivation (SD) is associated with an increased drive for sleep and is followed by compensatory rebound sleep. This is particularly true for NREM sleep, which may display a compensatory increase in both time and intensity. The NREM sleep intensity is reflected in the amount of slow waves in the EEG. 6-9 EEG slow-wave activity at the start of NREM sleep, i.e., the spectral power in the 1-4 Hz range, is a clear function of the duration of prior wakefulness. 10-13 SWA is highest at the beginning of sleep and gradually declines during the course of the sleep phase as the NREM sleep debt dissipates. Also REM sleep often displays a rebound increase after SD. It is still generally believed that REM sleep recovery
Journal of Sleep Research, 2011
have shown that brief SD immediately following a mild foot shock impairs consolidation of context... more have shown that brief SD immediately following a mild foot shock impairs consolidation of contextual fear memory as reflected in a reduced behavioral freezing response during re-exposure to the shock context later on. In the first part of this study, we examined whether this reduced freezing response is accompanied by an attenuated fear-induced activation of the hypothalamic-pituitary-adrenal (HPA) axis. Results show that 6 hours of SD immediately following the initial shock results in a diminished adrenal corticosterone (CORT) response upon re-exposure to the shock context the next day. In the second part, we established whether the attenuated freezing response in SD animals is associated with reduced activation of relevant brain areas known to be involved in the retrieval and expression of fear memory. Immunohistochemical analysis of brain slices showed that the normal increase in phosphorylation of the transcription factor cAMP response-element binding protein (CREB) upon reexposure to the shock context was reduced in SD animals in the CA1 region of the hippocampus and in the amygdala. In conclusion, brief SD impairs the consolidation of contextual fear memory. Upon reexposure to the context, this is reflected in a diminished behavioral freezing response, an attenuated HPA axis response, and a reduction of the normal increase of phosphorylated CREB (pCREB) expression in hippocampus and amygdala.
Journal of Neuroscience Methods, 2013
• The method used is effective in fragmenting sleep of mice for prolonged periods without behavio... more • The method used is effective in fragmenting sleep of mice for prolonged periods without behavioral adaptation.
Hormones and Behavior, 2012
There are large individual differences in the success rates of exercise intervention programs aim... more There are large individual differences in the success rates of exercise intervention programs aimed at the prevention and treatment of obesity-related disorders. In the present study, we tested the hypothesis that differences in coping style may impact the success rates of these intervention programs. We tested insulin responses before and after voluntary wheel running in both passive (insulin resistant) Roman Low Avoidance (RLA) and proactive (insulin sensitive) Roman High Avoidance (RHA) rats using intravenous glucose tolerance tests (IVGTTs). To control for a potential difference between voluntary and forced exercise, we also included RLA and RHA rats that were subjected to forced running. We found the following: 1) when given the opportunity to run voluntarily in a running wheel, passive RLA rats run more than proactively than RHA rats; 2) voluntary exercise leads to a normalization of insulin responses during an IVGTTs in RLA rats; and 3) there were no behavioral and physiological differences in efficacy between voluntary and forced running. We conclude that exercise, both forced and voluntary, is a successful lifestyle intervention for the treatment of hyperinsulinemia, especially in individuals with a passive coping style.
Current Biology, 2008
Endogenous biological clocks allow organisms to anticipate daily environmental cycles . The abili... more Endogenous biological clocks allow organisms to anticipate daily environmental cycles . The ability to achieve timeplace associations is key to the survival and reproductive success of animals. The ability to link the location of a stimulus (usually food) with time of day has been coined timeplace learning , but its circadian nature was only shown in honeybees [1] and birds . So far, an unambiguous circadian time-place-learning paradigm for mammals is lacking. We studied whether expression of the clock gene Cryptochrome (Cry), crucial for circadian timing, is a prerequisite for time-place learning. Time-place learning in mice was achieved by developing a novel paradigm in which food reward at specific times of day was counterbalanced by the penalty of receiving a mild footshock. Mice lacking the core clock genes Cry1 and Cry2 (Cry double knockout mice; Cry1 2/2 Cry2 2/2 ) learned to avoid unpleasant sensory experiences (mild footshock) and could locate a food reward in a spatial learning task (place preference). These mice failed, however, to learn time-place associations. This specific learning and memory deficit shows that a Cry-gene dependent circadian timing system underlies the utilization of time of day information. These results reveal a new functional role of the mammalian circadian timing system.
AJP: Regulatory, Integrative and Comparative Physiology, 2012
Physiology & Behavior, 2012
► The slowly rotating drum method effectively restricted sleep time in rats. ► Short sleep increa... more ► The slowly rotating drum method effectively restricted sleep time in rats. ► Short sleep increases energy expenditure but no change in food intake. ► Short sleep attenuates weight gain in rats. ► Plasma glucose, insulin and leptin levels were reduced, reflecting the nutritional status.