The effects of ethanol and the serotonin1A agonist ipsapirone on the expression of the serotonin1A receptor and several antiapoptotic proteins in fetal rhombencephalic neurons

Druse, Mary J.; Tajuddin, Nuzhath F.; Gillespie, Roberta A.; Le, Phong T.

doi:10.1016/j.brainres.2006.02.065

Cited by 33 publications

(43 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The dose used in those experiments (100 mM) was based on previously published studies that used EtOH treatment in a cell culture model system however, the physiological relevance of this high dose is questionable given that the blood alcohol level corresponding to the legal limit for driving (0.08%) is equivalent to about 25 mM [13], [14], [15], [16], [17], [18]. Therefore, we tested CRH promoter activity in the presence of varying doses of EtOH in order to establish the minimal effective dose.…”

Section: Resultsmentioning

confidence: 99%

Alcohol Dysregulates Corticotropin-Releasing-Hormone (CRH) Promoter Activity by Interfering with the Negative Glucocorticoid Response Element (nGRE)

2011

View full text Add to dashboard Cite

EtOH exposure in male rats increases corticotropin-releasing hormone (CRH) mRNA in the paraventricular nucleus of the hypothalamus (PVN), a brain region responsible for coordinating stress and anxiety responses. In this study we identified the molecular mechanisms involved in mediating these effects by examining the direct effects of EtOH on CRH promoter activity in a neuronal cell line derived from the PVN (IVB). In addition, we investigated the potential interactions of EtOH and glucocorticoids on the CRH promoter by concomitantly treating cells with EtOH and the glucocorticoid receptor (GR) antagonist RU486, and by sequentially deleting GR binding sites within glucocorticoid response element (GRE) on the CRH promoter. Cells were transiently transfected with a firefly luciferase reporter construct containing 2.5 kb of the rat wild type (WT) or mutated CRH promoter. Our results showed that EtOH treatment induced a biphasic response in CRH promoter activity. EtOH exposure for 0.5 h significantly decreased promoter activity compared to vehicle treated controls, whereas promoter activity was significantly increased after 2.0 h of EtOH exposure. Treatment with RU486, or deletion of the GR binding sites 1 and 2 within the GRE, abolished the EtOH-induced increase in the promoter activity, however did not affect EtOH-induced decrease in CRH promoter activity at an earlier time point. Overall, our data suggest that alcohol exposure directly regulates CRH promoter activity by interfering with the normal feedback mechanisms of glucocorticoids mediated by GR signaling at the GRE site of the CRH promoter.

show abstract

Section: Resultsmentioning

confidence: 99%

Alcohol Dysregulates Corticotropin-Releasing-Hormone (CRH) Promoter Activity by Interfering with the Negative Glucocorticoid Response Element (nGRE)

2011

View full text Add to dashboard Cite

show abstract

“…While their neuroprotective effects are undoubtedly due in part to their actions as classical antioxidants, the present studies raise the possibility that these effects might also involve the up-regulation of genes that encode pro-survival/anti-apoptotic proteins. Interestingly, this laboratory demonstrated that two additional neuroprotective agents, i.e., the 5-HT 1A agonist ipsapirone and S100B, both prevented ethanol-associated apoptosis and augmented expression of XIAP and either Bcl- xl or Bcl-2 (Druse et al, 2006; 2007). A common thread in the neuroprotective effects of three unrelated types of agents, i.e., antioxidants, ipsapirone, and S100B, might involve their ability to up-regulate the expression of these and possibly other neuroprotective genes.…”

Section: Discussionmentioning

confidence: 99%

Antioxidant neuroprotection against ethanol-induced apoptosis in HN2-5 cells

2009

Self Cite

View full text Add to dashboard Cite

Earlier studies from this and other laboratories show that ethanol induces apoptotic death of fetal and neonatal neurons. One mechanism that underlies these effects is the ethanol-associated reduction in the phosphatidylinositol 3′ kinase pro-survival pathway. Another mechanism involves the oxidative stress caused by the ethanol-associated increase in reactive oxygen species (ROS).In the present study, we used the murine HN2-5 hippocampal-derived cell line to investigate the effects of ethanol on ROS levels and apoptosis. We also investigated the potential neuroprotective effects of two structurally unrelated antioxidants: N-acetylcysteine (NAC) and melatonin. The results demonstrate that NAC blocked an ethanol-associated increase in ROS. In addition, NAC and melatonin prevented the augmentation of apoptosis in ethanol-treated neurons. Both antioxidants significantly elevated the expression of the anti-apoptotic gene XIAP in ethanol-treated and/or control neurons and melatonin increased Bcl-2 expression in ethanol-treated neurons. Thus, it is possible that the neuroprotective effects of NAC and melatonin involve their ability to augment the expression of one or more anti-apoptotic gene as well as their classical antioxidant actions. Additional studies are needed to establish the effectiveness of these antioxidants to prevent the loss of neurons which accompanies in utero exposure to ethanol.

show abstract

“…In addition, it reduces brainstem 5-HT levels, decreases the 5-HT neuronal density in the raph e, and decreases 5-HT innervation of target forebrain areas (Druse, Kuo, & Tajuddin, 1991;Kim et al, 2005;Zhou et al, 2001). Serotonin agonists also prevent several adverse effects of alcohol upon the 5-HT brainstem development (Druse, Tajuddin, Gillespie, & Le, 2006). In regards to prenatal exposure to cigarette smoking, nicotine, the major neurotoxic component, passes the placenta and fetal blood-brain barrier to bind to the endogenous nicotinic receptors in the fetal brain.…”

Section: Figurementioning

confidence: 99%

Brainstem mechanisms underlying the sudden infant death syndrome: Evidence from human pathologic studies

Kinney

2009

Developmental Psychobiology

108

View full text Add to dashboard Cite

The brainstem hypothesis is one of the leading hypotheses concerning the sudden infant death syndrome (SIDS). It states that SIDS, or an important subset of SIDS, is due to abnormal brainstem mechanisms in the control of respiration, chemosensitivity, autonomic regulation, and/or arousal which impairs the infant's response to life-threatening, but often occurring, stressors during sleep (e.g., hypoxia, hypercarbia, asphyxia, hyperthermia) and leads to sudden death in a vulnerable developmental period. In this review, we summarize neuropathologic evidence from SIDS cases that support this hypothesis, beginning with the seminal report of subtle brainstem gliosis three decades ago. We focus upon recent neurochemical studies in our laboratory concerning the neurotransmitter serotonin (5-HT) and its key role in mediating protective responses to homeostatic stressors via medullary circuits. The possible fetal origin of brainstem defects in SIDS is reviewed, including evidence for adverse effects of prenatal exposure to maternal cigarette smoking and alcohol upon the postnatal development of human brainstem 5-HT pathways.

show abstract

The effects of ethanol and the serotonin1A agonist ipsapirone on the expression of the serotonin1A receptor and several antiapoptotic proteins in fetal rhombencephalic neurons

Cited by 33 publications

References 45 publications

Alcohol Dysregulates Corticotropin-Releasing-Hormone (CRH) Promoter Activity by Interfering with the Negative Glucocorticoid Response Element (nGRE)

Alcohol Dysregulates Corticotropin-Releasing-Hormone (CRH) Promoter Activity by Interfering with the Negative Glucocorticoid Response Element (nGRE)

Antioxidant neuroprotection against ethanol-induced apoptosis in HN2-5 cells

Brainstem mechanisms underlying the sudden infant death syndrome: Evidence from human pathologic studies

Contact Info

Product

Resources

About