In utero ethanol exposure decreased the density of serotonin neurons. Maternal ipsapirone treatment exerted a protective effect

Tajuddin, Nuzhath F.; Druse, Mary J.

doi:10.1016/s0165-3806(99)00102-9

Cited by 61 publications

(51 citation statements)

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“…Reduced concentrations of 5-HT and its metabolite, 5-HIAA, have been observed throughout the brain in alcohol-exposed animals (Druse et al 1991). In a series of studies, Druse and colleagues have demonstrated that maternal treatment with 5-HT 1A agonists, buspirone and ipsapirone, mitigated the ethanol-induced damage to the 5-HT system (Eriksen and Druse 2001;Tajuddin and Druse 1999).…”

Section: -Ht 1a Agonistsmentioning

confidence: 99%

From Research to Practice: An Integrative Framework for the Development of Interventions for Children with Fetal Alcohol Spectrum Disorders

Kodituwakku

2011

Neuropsychol Rev

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Since fetal alcohol syndrome was first described over 35 years ago, considerable progress has been made in the delineation of the neurocognitive profile in children with prenatal alcohol exposure. Preclinical investigators have made impressive strides in elucidating the mechanisms of alcohol teratogenesis and in testing the effectiveness of pharmacological agents and dietary supplementation in the amelioration of alcohol-induced deficits. Despite these advances, only limited progress has been made in the development of evidence-based comprehensive interventions for functional impairment in alcohol-exposed children. Having performed a search in PubMed and PsycINFO using key words, interventions, treatment, fetal alcohol syndrome, prenatal alcohol exposure, and fetal alcohol spectrum disorders, we found only 12 papers on empirically-based interventions. Only two of these interventions had been replicated and none met the criteria of "well-established," as defined by Chambless and Hollon (Journal of Consulting and Clinical Psychology 66(1):7-18, 1998). There has been only limited cross-fertilization of ideas between preclinical and clinical research with regard to the development of interventions. Therefore, we propose a framework that allows integrating data from preclinical and clinical investigations to develop comprehensive intervention programs for children with fetal alcohol spectrum disorders. This framework underscores the importance of multi-level evaluations and interventions.

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Section: -Ht 1a Agonistsmentioning

confidence: 99%

From Research to Practice: An Integrative Framework for the Development of Interventions for Children with Fetal Alcohol Spectrum Disorders

Kodituwakku

2011

Neuropsychol Rev

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“…In vitro and in vivo studies of animal models show that ethanol damages the developing CNS by reducing neurons in the cortex, cerebellum, hippocampus, and dorsal and median raphe (Marcussen, et al, 1994;Goodlett and Eilers, 1997;Tajuddin and Druse, 1999;Jacobs and Miller, 2001;Moulder, et al, 2002). Reportedly, a single high dose of ethanol, administered during a vulnerable developmental period, causes neurodegeneration in the rodent forebrain, caudate nucleus, nucleus accumbens, hippocampus, amygdala, thalamus, and cerebellum (Ikonomidou, et al, 2000;Dikranian et al, 2005.…”

Section: Introductionmentioning

confidence: 99%

“…In fact, this laboratory finds that the loss of the developing serotonin (5-HT) neurons of the dorsal and median raphe region (Tajuddin and Druse, 1999; is caused by ethanol-associated apoptosis (Druse et al, 2004;2007). Moreover, these effects are accompanied by a decrease in the activity of the phosphatidylinositol 3'kinase (PI-3K) → pAkt pro-survival pathway and the downstream reduction in the expression of NF-kB dependent genes that encode pro-survival/anti-apoptotic proteins (Druse et al, 2005, e.g.…”

Section: Introductionmentioning

confidence: 99%

Antioxidants prevent ethanol-associated apoptosis in fetal rhombencephalic neurons

Antonio

Druse

2008

Brain Research

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It is well known that ethanol damages the developing nervous system by augmenting apoptosis. Previously, this laboratory reported that ethanol augments apoptosis in fetal rhombencephalic neurons, and that the increased apoptosis is associated with reduced activity of the phosphatidylinositol 3'kinase pathway and downstream expression of pro-survival genes. Other laboratories have shown that another mechanism by which ethanol induces apoptosis in developing neurons is through the generation of reactive oxygen species (ROS) and the associated oxidative stress.The present study used an in vitro model to investigate the potential neuroprotective effects of several antioxidants against ethanol-associated apoptosis in fetal rhombencephalic neurons. The investigated antioxidants included three phenolics: (-)-epigallocatechin-3-gallate (EGCG), a flavanoid polyphenol found in green tea; curcumin, found in tumeric; and resveratrol (3,5,4'-trihydroxystilbene), a component of red wine. Additional antioxidants, including melatonin, a naturally occurring indole, and α-lipoic acid, a naturally occurring dithiol, were also investigated.These studies demonstrated that a 24-hour treatment of fetal rhombencephalic neurons with 75 mM ethanol caused a 3-fold increase in the percentage of apoptotic neurons. However, co-treatment of these cultures with any of the five different antioxidants prevented ethanol-associated apoptosis. Antioxidant treatment did not alter the extent of apoptosis in control neurons, i.e., those cultured in the absence of ethanol. These studies showed that several classes of antioxidants can exert neuroprotection against ethanol-associated apoptosis in fetal rhombencephalic neurons.

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“…Recent work in this laboratory showed that the same treatment also reduced the number of 5-HT neurons and retards their migration in the brain of E15 C57BL mice [49,50]. Recently, it has been shown that alcohol exposure prior to conception and throughout pregnancy reduced the density of 5-HT-immunoreactive neurons in the dorsal raphe and B9 in postnatal day 5 rats [42]. It would, therefore, be of interest to examine if alcohol affects the development of the 5-HT system in a more defined stage (namely, E8-15) and if the neurons are already reduced in earlier development.…”

mentioning

confidence: 99%

“…The neurotoxic effects of alcohol may also include disruption of several neurotransmitter systems such as the serotonergic [42,50], dopaminergic [7,9], noradrenergic [7], glutamatergic [15,18], histaminic [33] and cholinergic systems [27,38,39]. In this present work, we focused on the serotonin (5-HT) system because earlier evidence indicates that 5-HT can act as a regulatory or trophic factor during neurogenesis for the development of 5-HT and other neurons [8,13,17,24,26,45].…”

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confidence: 99%

Alcohol Deters the Outgrowth of Serotonergic Neurons at Midgestation

2001

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We have previously demonstrated that treatment of pregnant C57BL mice from gestation days 8 to 14 with alcohol with 20% ethanol-derived calories (EDC) reduced the number of serotonin (5-HT) neurons and retarded their migration in the fetal brains. In the present study, we obtained similar results with the use of 25% EDC and extended our previous findings by demonstrating that besides the alteration of the number of 5-HT neurons, prenatal alcohol exposure also affects their projecting fibers in their early development. Pregnant C57BL mice were divided into an alcohol-exposed (ALC) group given 25% EDC (4.49%, v/v), a pair-fed group to the ethanol-fed group (PF) and a chow-fed group (Chow). The PF and Chow groups served as controls. Our results showed that in the ALC group, when compared with the control groups, prenatal alcohol exposure with 25% EDC reduced the number of 5-HT-immunoreactive neurons in both the median and dorsal raphe, and the amount of 5-HT-immunoreactive fibers in the medial forebrain bundle (MFB). The diameter of the 5-HT-immunoreactive MFB was also reduced as a result of treatment. No significant differences of the above parameters were found between the PF and Chow groups. The previous and present work confirmed that alcohol reduces the normal formation and growth of 5-HT neurons in the midbrain. Furthermore, the projection of 5-HT fibers, in density as well as in distribution, is reduced in the major trajectory bundle. This may affect the amount of 5-HT fibers available to the forebrain. In light of the importance of the 5-HT system in brain development, alcohol may affect the growth of the forebrain through its effect on 5-HT signaling.

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In utero ethanol exposure decreased the density of serotonin neurons. Maternal ipsapirone treatment exerted a protective effect

Cited by 61 publications

References 63 publications

From Research to Practice: An Integrative Framework for the Development of Interventions for Children with Fetal Alcohol Spectrum Disorders

From Research to Practice: An Integrative Framework for the Development of Interventions for Children with Fetal Alcohol Spectrum Disorders

Antioxidants prevent ethanol-associated apoptosis in fetal rhombencephalic neurons

Alcohol Deters the Outgrowth of Serotonergic Neurons at Midgestation

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