- Email: [email protected]
16. Biobehavioral correlates of overweight and obesity in postpartum women
4
Abstracts / Brain, Behavior, and Immunity 22 (2008) 1–7
Fever is an organized, adaptive strategy critical to host survival, but can be dangerous if uncontrolled. Endotoxin tolerance, in which individuals receiving a low dose of endotoxin are protected from a subsequent high dose, is well documented, and is also likely adaptive. Here we assessed whether infection early in life influences the response to infection in adulthood, given evidence that events occurring during the perinatal period may ‘‘program” later physiology and behavior. In Exp. 1, rats infected neonatally with Escherichia coli exhibited a slight but significant increase in fever and sickness behavior following a low dose of lipopolysaccharide (LPS) in adulthood compared to controls. Eight days after the LPS injection, the same rats received a high dose of live E. coli. Neonatally-infected rats exhibited a markedly longer fever compared to controls. In Exp. 2, fever to a single high dose of E. coli in adulthood did not dier as a consequence of early infection, suggesting that the dierence in Exp. 1 was a lack of LPS tolerance in early-infected rats. In Exp. 3, TNF±; expression in peripheral macrophages was higher basally in early-infected rats, but tolerance was observed in both groups. In Exp. 4, cyclooxygenase-2 expression, a rate-limiting enzyme in fever, and a microglial activation marker within the preoptic area of the hypothalamus were significantly higher in neonatally-infected rats challenged with LPS and subsequent E. coli in adulthood compared to all other groups. In sum, early-life infection appears to sensitize the brain to each subsequent challenge in adulthood. doi:10.1016/j.bbi.2008.04.018
16. Biobehavioral correlates of overweight and obesity in postpartum women Maureen Groer E-mail: [email protected] In a psychoneuroimmunological study of the postpartum, overweight and obesity were present in 57% of 200 mothers. Therefore we asked whether BMI was associated with stress and immune variables that were measured. Mothers were measured in their homes at approximately 5 weeks postpartum, completing stress, mood, and health questionnaires and providing a blood sample. Participants were healthy, had no chronic illnesses, had a full-term uncomplicated delivery, and about half were exclusively breastfeeding. Higher BMI was associated with lower socioeconomic status and increased incidence of Caesarean section. There was a tendency for higher BMI to be associated with greater perceived stress, depression, and anxiety. Decreased serum Interferon-c and IL-2 levels were associated with higher BMI, independently of stress. However inflammatory biomarkers IL-6, TNF-±; and C-reactive protein did not dier by BMI. Overweight and obesity did not increase infections reports. There was an association of higher BMI with elevated Thyroid-Stimulating Hormone levels, suggesting postpartum hypothyroidism. The data suggest that overweight or obesity is distressing to postpartum mothers, and may impact Th1/Th2 balance. This postpartal stage is normally associated with upregulated innate immunity and overweight or obesity did not seem to alter inflammation biomarkers. The postpartum may be a somewhat protected period, and additional weight is tolerated because of the metabolic demands of lactation, sleep deficits, and healing during this time of life. Further longitudinal work is needed to more carefully examine the risks associated with overweight and obesity during the postpartum period. doi:10.1016/j.bbi.2008.04.019
18. Minocycline attenuates lipopolysaccharide (LPS)-induced brain cytokine expression, social withdrawal, and anhedonia Christopher Henry a,*, Yan Huang a, Angela Wynne a, Justin Himler a, Jonathan Godbout a,b a
Department of Molecular Virology, Immunology and Medical Genetics, The Ohio State University, Columbus, OH 43210, USA b Institute for Behavioral Medicine Research, The Ohio State University, Columbus, OH 43210, USA * Corresponding author. E-mail: [email protected]
Activation of the peripheral innate immune system stimulates the production of CNS cytokines that modulate the behavioral symptoms of sickness. Excessive or prolonged production of CNS cytokines by microglia, however, may cause long-lasting behavioral and cognitive complications. The purpose of this study was to determine if minocycline, a purported microglial inhibitor, attenuates LPS-induced neuroinflammation, sickness behavior, and anhedonia in mice. In an initial study we confirmed that minocycline blocked LPS-stimulated inflammatory cytokine production in the BV2 and N13 microglia-derived cell lines. In the next set of experiments we confirmed that intraperitoneal (i.p.) lipopolysaccharide (LPS) injection (0.33 mg/kg) induced a sickness response in BALB/c mice characterized by increased social withdrawal, body weight loss, and anorexia 24 h post injection. These symptoms were attenuated by minocycline pretreatment (50 mg/kg/day for 3 days, i.p.). Moreover, LPS caused anhedonia in mice 24 h post challenge, as determined by a marked reduction in preference for a 2% sucrose solution over drinking water. This LPS-induced anhedonia was inhibited in mice pretreated with minocycline. Furthermore, plasma IL-6 levels at 4 h and 8 h post LPS injection were reduced by minocycline pretreatment while plasma IL-1b levels were reduced at 8 h but not at 4 h. Finally, the minocycline enhanced recovery from LPS-induced sickness behavior was paralleled by reduced levels of IL-1b, IL-6, and indoleamine-2,3-dioxygenase in the cortex and hippocampus. Taken together, these data indicate that minocycline mitigates inflammatory cytokine production in the brain and modulates the cytokine-associated changes in behavior. doi:10.1016/j.bbi.2008.04.020
19. Young adult APOE e4 carriers show a stress-induced decline in ‘‘hot cognition” and sIL-6r, but not IL-6 Andrine Lemieux *, Douglas Walton, Jon Nelson The College of St. Scholastica * Corresponding author. E-mail: [email protected] The apolipoprotein E epsilon 4 gene (APOE e4) has been extensively studied in the late life development of Alzheimer’s Disease, but early investigators of this gene refer to it a ‘‘silent gene” in young adults. It’s role as a stress-vulnerability gene in young adults has not been investigated. It was hypothesized here that APOE e4+ young adults tested in a developmentally appropriate manner would show stress-related cognitive deficits and elevations in cortisol, IL-6 and sIL-6r. Fifty-eight young adults (18–39 years) were evaluated in an exam stress paradigm. Outcome measures included cognitive functions (reasoning, memory and attention), as well as plasma cortisol, IL-6 and sIL-6r. Twenty-six young adults were APOE e4+ and 32 were APOE e4 . No gene eects were seen for cortisol, but gene X stress interactions were significant for both cognitive testing (p < .05) and sIL-6r (p < .05). Unexpectedly APOE e4+ subjects showed impaired emotion-based reasoning at both sessions, while APOE e4 counter-
Abstracts / Brain, Behavior, and Immunity 22 (2008) 1–7
Fever is an organized, adaptive strategy critical to host survival, but can be dangerous if uncontrolled. Endotoxin tolerance, in which individuals receiving a low dose of endotoxin are protected from a subsequent high dose, is well documented, and is also likely adaptive. Here we assessed whether infection early in life influences the response to infection in adulthood, given evidence that events occurring during the perinatal period may ‘‘program” later physiology and behavior. In Exp. 1, rats infected neonatally with Escherichia coli exhibited a slight but significant increase in fever and sickness behavior following a low dose of lipopolysaccharide (LPS) in adulthood compared to controls. Eight days after the LPS injection, the same rats received a high dose of live E. coli. Neonatally-infected rats exhibited a markedly longer fever compared to controls. In Exp. 2, fever to a single high dose of E. coli in adulthood did not dier as a consequence of early infection, suggesting that the dierence in Exp. 1 was a lack of LPS tolerance in early-infected rats. In Exp. 3, TNF±; expression in peripheral macrophages was higher basally in early-infected rats, but tolerance was observed in both groups. In Exp. 4, cyclooxygenase-2 expression, a rate-limiting enzyme in fever, and a microglial activation marker within the preoptic area of the hypothalamus were significantly higher in neonatally-infected rats challenged with LPS and subsequent E. coli in adulthood compared to all other groups. In sum, early-life infection appears to sensitize the brain to each subsequent challenge in adulthood. doi:10.1016/j.bbi.2008.04.018
16. Biobehavioral correlates of overweight and obesity in postpartum women Maureen Groer E-mail: [email protected] In a psychoneuroimmunological study of the postpartum, overweight and obesity were present in 57% of 200 mothers. Therefore we asked whether BMI was associated with stress and immune variables that were measured. Mothers were measured in their homes at approximately 5 weeks postpartum, completing stress, mood, and health questionnaires and providing a blood sample. Participants were healthy, had no chronic illnesses, had a full-term uncomplicated delivery, and about half were exclusively breastfeeding. Higher BMI was associated with lower socioeconomic status and increased incidence of Caesarean section. There was a tendency for higher BMI to be associated with greater perceived stress, depression, and anxiety. Decreased serum Interferon-c and IL-2 levels were associated with higher BMI, independently of stress. However inflammatory biomarkers IL-6, TNF-±; and C-reactive protein did not dier by BMI. Overweight and obesity did not increase infections reports. There was an association of higher BMI with elevated Thyroid-Stimulating Hormone levels, suggesting postpartum hypothyroidism. The data suggest that overweight or obesity is distressing to postpartum mothers, and may impact Th1/Th2 balance. This postpartal stage is normally associated with upregulated innate immunity and overweight or obesity did not seem to alter inflammation biomarkers. The postpartum may be a somewhat protected period, and additional weight is tolerated because of the metabolic demands of lactation, sleep deficits, and healing during this time of life. Further longitudinal work is needed to more carefully examine the risks associated with overweight and obesity during the postpartum period. doi:10.1016/j.bbi.2008.04.019
18. Minocycline attenuates lipopolysaccharide (LPS)-induced brain cytokine expression, social withdrawal, and anhedonia Christopher Henry a,*, Yan Huang a, Angela Wynne a, Justin Himler a, Jonathan Godbout a,b a
Department of Molecular Virology, Immunology and Medical Genetics, The Ohio State University, Columbus, OH 43210, USA b Institute for Behavioral Medicine Research, The Ohio State University, Columbus, OH 43210, USA * Corresponding author. E-mail: [email protected]
Activation of the peripheral innate immune system stimulates the production of CNS cytokines that modulate the behavioral symptoms of sickness. Excessive or prolonged production of CNS cytokines by microglia, however, may cause long-lasting behavioral and cognitive complications. The purpose of this study was to determine if minocycline, a purported microglial inhibitor, attenuates LPS-induced neuroinflammation, sickness behavior, and anhedonia in mice. In an initial study we confirmed that minocycline blocked LPS-stimulated inflammatory cytokine production in the BV2 and N13 microglia-derived cell lines. In the next set of experiments we confirmed that intraperitoneal (i.p.) lipopolysaccharide (LPS) injection (0.33 mg/kg) induced a sickness response in BALB/c mice characterized by increased social withdrawal, body weight loss, and anorexia 24 h post injection. These symptoms were attenuated by minocycline pretreatment (50 mg/kg/day for 3 days, i.p.). Moreover, LPS caused anhedonia in mice 24 h post challenge, as determined by a marked reduction in preference for a 2% sucrose solution over drinking water. This LPS-induced anhedonia was inhibited in mice pretreated with minocycline. Furthermore, plasma IL-6 levels at 4 h and 8 h post LPS injection were reduced by minocycline pretreatment while plasma IL-1b levels were reduced at 8 h but not at 4 h. Finally, the minocycline enhanced recovery from LPS-induced sickness behavior was paralleled by reduced levels of IL-1b, IL-6, and indoleamine-2,3-dioxygenase in the cortex and hippocampus. Taken together, these data indicate that minocycline mitigates inflammatory cytokine production in the brain and modulates the cytokine-associated changes in behavior. doi:10.1016/j.bbi.2008.04.020
19. Young adult APOE e4 carriers show a stress-induced decline in ‘‘hot cognition” and sIL-6r, but not IL-6 Andrine Lemieux *, Douglas Walton, Jon Nelson The College of St. Scholastica * Corresponding author. E-mail: [email protected] The apolipoprotein E epsilon 4 gene (APOE e4) has been extensively studied in the late life development of Alzheimer’s Disease, but early investigators of this gene refer to it a ‘‘silent gene” in young adults. It’s role as a stress-vulnerability gene in young adults has not been investigated. It was hypothesized here that APOE e4+ young adults tested in a developmentally appropriate manner would show stress-related cognitive deficits and elevations in cortisol, IL-6 and sIL-6r. Fifty-eight young adults (18–39 years) were evaluated in an exam stress paradigm. Outcome measures included cognitive functions (reasoning, memory and attention), as well as plasma cortisol, IL-6 and sIL-6r. Twenty-six young adults were APOE e4+ and 32 were APOE e4 . No gene eects were seen for cortisol, but gene X stress interactions were significant for both cognitive testing (p < .05) and sIL-6r (p < .05). Unexpectedly APOE e4+ subjects showed impaired emotion-based reasoning at both sessions, while APOE e4 counter-