Novel peptides prevent alcohol-induced spatial learning deficits and proinflammatory cytokine release in a mouse model of fetal alcohol syndrome

Vink, Joy; Auth, Jonathan; Abebe, Daniel; Brenneman, Douglas E.; Spong, Catherine Y.

doi:10.1016/j.ajog.2005.02.101

Cited by 53 publications

(42 citation statements)

References 24 publications

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“…Furthermore, cocultures of prenatal ethanol-exposed astrocytes with control neurons caused a marked decrease in neuronal growth, differentiation, and synaptic connections relative to the cocultures with control astrocytes, effects that were reverted by the addition of NAP (Pascual and Guerri, 2007). Other studies showed that prenatal NAP administration, in combination with ADNF-9 (SALLRSIPA), prevented the alcohol-induced spatial learning deficits and attenuated alcohol-induced proinflammatory cytokine increase in a model of fetal alcohol syndrome (Vink et al, 2005).…”

Section: Discussionmentioning

confidence: 93%

Activity-Dependent Neuroprotective Protein Snippet NAP Reduces Tau Hyperphosphorylation and Enhances Learning in a Novel Transgenic Mouse Model

Vulih-Shultzman¹,

Pinhasov²,

Mandel³

et al. 2007

J Pharmacol Exp Ther

202

275

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Activity-dependent neuroprotective protein (ADNP) differentially interacts with chromatin to regulate essential genes. Because complete ADNP deficiency is embryonic lethal, the outcome of partial ADNP deficiency was examined. ADNP ϩ/Ϫ mice exhibited cognitive deficits, significant increases in phosphorylated tau, tangle-like structures, and neurodegeneration compared with ADNP ϩ/ϩ mice. Increased tau hyperphosphorylation is known to cause memory impairments in neurodegenerative diseases associated with tauopathies, including the most prevalent Alzheimer's disease. The current results suggest that ADNP is an essential protein for brain function and plays a role in normal cognitive performance. ADNP-deficient mice offer an ideal paradigm for evaluation of cognitive enhancers. NAP (NAPVSIPQ) is a peptide derived from ADNP that interacts with microtubules and provides potent neuroprotection. NAP treatment partially ameliorated cognitive deficits and reduced tau hyperphosphorylation in the ADNP ϩ/Ϫ mice. NAP is currently in phase II clinical trials assessing effects on mild cognitive impairment.

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Section: Discussionmentioning

confidence: 93%

Activity-Dependent Neuroprotective Protein Snippet NAP Reduces Tau Hyperphosphorylation and Enhances Learning in a Novel Transgenic Mouse Model

Vulih-Shultzman¹,

Pinhasov²,

Mandel³

et al. 2007

J Pharmacol Exp Ther

202

275

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“…For example, treatment of Down syndrome cortical neurons with NAP and SAL has been found to produce a reduction of degenerative processes (Busciglio et al 2007). A number of investigators have documented that combinatorial treatment with NAP and SAL prevented the deleterious effects of alcohol on the developing fetus (Parnell et al 2007;Spong et al 2001;Vink et al 2005;Zhou et al 2004). Spong et al (2001) found that the prenatal administration of NAP+SAL to alcohol-treated pregnant mice significantly increased the survival rates of fetuses.…”

Section: -Ht 1a Agonistsmentioning

confidence: 96%

“…Spong et al (2001) found that the prenatal administration of NAP+SAL to alcohol-treated pregnant mice significantly increased the survival rates of fetuses. Prenatal administration of NAP +SAL has also been found to prevent alcohol-induced spatial learning difficulties (Vink et al 2005) and reduce birth defects such as ocular anomalies (Parnell et al 2007). …”

Section: -Ht 1a Agonistsmentioning

confidence: 97%

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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“…Even a brief exposure to ethanol during gestation can produce an imbalance in the brain's intracellular redox state [43]. Such imbalances correlate with FASD-relevant spatial learning deficits [44]. We have previously identified a delay in spatial learning in second-trimester ethanol-exposed mice [10].…”

Section: Discussionmentioning

confidence: 99%

Molecular Changes during Neurodevelopment following Second-Trimester Binge Ethanol Exposure in a Mouse Model of Fetal Alcohol Spectrum Disorder: From Immediate Effects to Long-Term Adaptation

Mantha

Laufer

Singh³

2014

Dev Neurosci

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Fetal alcohol spectrum disorder (FASD) is an umbrella term that refers to a wide range of behavioral and cognitive deficits resulting from prenatal alcohol exposure. It involves changes in brain gene expression that underlie lifelong FASD symptoms. How these changes are achieved from immediate to long-term effects, and how they are maintained, is unknown. We have used the C57BL/6J mouse to assess the dynamics of genomic alterations following binge alcohol exposure. Ethanol-exposed fetal (short-term effect) and adult (long-term effect) brains were assessed for gene expression and microRNA (miRNA) changes using Affymetrix mouse arrays. We identified 48 and 68 differentially expressed genes in short- and long-term groups, respectively. No gene was common between the 2 groups. Short-term (immediate) genes were involved in cellular compromise and apoptosis, which represent ethanol's toxic effects. Long-term genes were involved in various cellular functions, including epigenetics. Using quantitative RT-PCR, we confirmed the downregulation of long-term genes: Camk1g, Ccdc6, Egr3, Hspa5, and Xbp1. miRNA arrays identified 20 differentially expressed miRNAs, one of which (miR-302c) was confirmed. miR-302c was involved in an inverse relationship with Ccdc6. A network-based model involving altered genes illustrates the importance of cellular redox, stress and inflammation in FASD. Our results also support a critical role of apoptosis in FASD, and the potential involvement of miRNAs in the adaptation of gene expression following prenatal ethanol exposure. The ultimate molecular footprint involves inflammatory disease, neurological disease and skeletal and muscular disorders as major alterations in FASD. At the cellular level, these processes represent abnormalities in redox, stress and inflammation, with potential underpinnings to anxiety.

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Novel peptides prevent alcohol-induced spatial learning deficits and proinflammatory cytokine release in a mouse model of fetal alcohol syndrome

Cited by 53 publications

References 24 publications

Activity-Dependent Neuroprotective Protein Snippet NAP Reduces Tau Hyperphosphorylation and Enhances Learning in a Novel Transgenic Mouse Model

Activity-Dependent Neuroprotective Protein Snippet NAP Reduces Tau Hyperphosphorylation and Enhances Learning in a Novel Transgenic Mouse Model

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

Molecular Changes during Neurodevelopment following Second-Trimester Binge Ethanol Exposure in a Mouse Model of Fetal Alcohol Spectrum Disorder: From Immediate Effects to Long-Term Adaptation

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