Related Experiment Video

Updated: Jun 28, 2026

Experimental Methods for Testing the Effects of Neurotrophic Peptide, ADNF-9, Against Alcohol-induced Apoptosis during Pregnancy in C57BL/6 Mice
09:50

Experimental Methods for Testing the Effects of Neurotrophic Peptide, ADNF-9, Against Alcohol-induced Apoptosis during Pregnancy in C57BL/6 Mice

Published on: April 24, 2013

Adenylyl cyclases types 1 and 8 promote pro-survival pathways after ethanol exposure in the neonatal brain

Alana C Conti1, Chainllie Young, John W Olney

  • 1Department of Pediatrics, Washington University in St. Louis, St. Louis, MO 63110, USA. conti_a@kids.wustl.edu

Neurobiology of Disease
|November 11, 2008
PubMed

Insights

Adenylyl cyclases 1 and 8 (AC1/AC8) protect the brain from ethanol-induced cell death. Deleting these enzymes increases neurodegeneration, suggesting they are key to preventing Fetal Alcohol Syndrome symptoms.

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Developmental Biology

Background:

  • Fetal alcohol exposure causes developmental disabilities, but molecular factors influencing severity are unknown.
  • Adenylyl cyclases 1 and 8 (AC1/AC8) are implicated in ethanol's effects, but their role in acute neurodegeneration is unclear.

Purpose of the Study:

  • To investigate the role of AC1 and AC8 in acute ethanol-induced neurodegeneration.
  • To determine if AC1/AC8 are critical for primary or secondary mechanisms of ethanol neurotoxicity.

Main Methods:

  • Utilized knockout mice lacking AC1 and AC8 (DKO) and wild-type (WT) controls.
  • Examined apoptosis levels in the striatum following ethanol exposure.
  • Assessed phosphorylation of pro-survival proteins: IRS-1, Akt, and ERK.

Main Results:

  • DKO mice showed significantly increased striatal apoptosis compared to WT controls.
  • Enhanced neuroapoptosis in DKO mice was linked to reduced phosphorylation of IRS-1, Akt, and ERK.
  • AC1/AC8 appear crucial for activating cell survival pathways acutely after ethanol exposure.

Conclusions:

  • AC1 and AC8 are critical for activating cell survival signaling pathways in response to acute ethanol exposure.
  • These enzymes may directly influence the severity of Fetal Alcohol Syndrome symptoms.
  • Targeting AC1/AC8 pathways could offer therapeutic strategies for FASD.

More Related Videos

Construction of Vapor Chambers Used to Expose Mice to Alcohol During the Equivalent of all Three Trimesters of Human Development15:27

Construction of Vapor Chambers Used to Expose Mice to Alcohol During the Equivalent of all Three Trimesters of Human Development

Published on: July 13, 2014

Rapid Detection of Neurodevelopmental Phenotypes in Human Neural Precursor Cells (NPCs)10:47

Rapid Detection of Neurodevelopmental Phenotypes in Human Neural Precursor Cells (NPCs)

Published on: March 2, 2018

Related Concept Videos

GPCRs Regulate Adenylyl Cylase Activity01:09

GPCRs Regulate Adenylyl Cylase Activity

Some GPCRs transmit signals through adenylyl cyclase (AC), a transmembrane enzyme. AC helps synthesize second messenger cyclic adenosine monophosphate (cAMP). AC catalyzes cyclization reaction and converts ATP to cAMP by releasing a pyrophosphate. The pyrophosphate is further hydrolyzed to phosphate by the enzyme pyrophosphatase, which drives cAMP synthesis to completion. However, cAMP is rapidly degraded to 5′ AMP by the enzymes phosphodiesterase (PDE), preventing overstimulation of cells.
Two...
Intracellular Signaling Cascades01:24

Intracellular Signaling Cascades

Once a ligand binds to a receptor, the signal is transmitted through the membrane and into the cytoplasm. The continuation of a signal in this manner is called signal transduction. Signal transduction only occurs with cell-surface receptors, which cannot interact with most components of the cell, such as DNA. Only internal receptors can interact directly with DNA in the nucleus to initiate protein synthesis. When a ligand binds to its receptor, conformational changes occur that affect the...
Regulation of Angiogenesis and Blood Supply01:24

Regulation of Angiogenesis and Blood Supply

Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits.  Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl hydroxylase and factor...
cAMP-dependent Protein Kinase Pathways01:25

cAMP-dependent Protein Kinase Pathways

Cyclic Adenosine Monophosphate (cAMP) is an essential second messenger that activates protein kinase A (PKA) and regulates various biological processes. A single epinephrine molecule binds to GPCR and activates several heterotrimeric G proteins, each stimulating multiple adenylyl cyclase, amplifying the signal, and synthesizing large numbers of cAMP molecules. Small changes in cAMP concentration affect PKA activity. The binding of four cAMP molecules induces a conformational change in PKA,...
Amplifying Signals via Enzymatic Cascade01:22

Amplifying Signals via Enzymatic Cascade

When a ligand binds to a cell-surface receptor, the receptor's intracellular domain changes shape, which may either activate its enzyme function or allow its binding to other molecules. The initial signal is amplified by most signal transduction pathways. This means that a single ligand molecule can activate multiple molecules of a downstream target. Proteins that relay a signal are most commonly phosphorylated at one or more sites, activating or inactivating the protein. Kinases catalyze the...
Interactions Between Signaling Pathways01:19

Interactions Between Signaling Pathways

Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...