A new study provides evidence that endocannabinoids, natural compounds that are chemically similar to the active ingredient in marijuana, play a role in the development of Fetal Alcohol Spectrum Disorders (FASD). Researchers led by Balapal S. Basavarajappa (aka: Basavaraj S. Balapal), Ph.D., of the Nathan Kline Institute for Psychiatric Research and New York State Psychiatric Institute, investigated the effect of alcohol on the endocannabinoid system and how those effects influence brain development in mice. The molecules and receptors that comprise the body’s endocannabinoid system work together to affect physiological processes such as brain development, appetite, pain, mood, and memory – the very processes also affected by using marijuana.

In this study, published in the April 10, 2013 issue of the Journal of Neuroscience, researchers exposed 7-day-old mice to binge-like amounts of alcohol to examine the resulting changes in the brain’s structure and functions. In terms of brain development, this is comparable to exposing a human in the third trimester of fetal development to alcohol. What they found is that the endocannabinoid anandamide (AEA) and its receptor, CB1, both increase in response to alcohol. Elevated AEA and CB1 receptor causes the extracellular signal-regulated kinases (ERK 1/2) to change from its active, or phosphorylated, form to its inactive or dephosphorylated form. The authors hypothesized that it is this change in ERK 1/2 that causes neurodegeneration in neonates and deficits in synaptic plasticity and cognitive function in adults that are characteristic of FASD.

The researchers further tested this hypothesis by blocking CB1 receptors in two ways. One was to pharmacologically block CB1 activity with an antagonist. The other was by using mice that were genetically engineered to have no CB1 receptor. Both of these manipulations prevented alcohol-induced neurodegeneration in neonates and long-lasting synaptic and memory deficits in adult mice.

Dr. Shivakumar Subbanna, the study’s first author explains that “elevated AEA/CB1 receptor signaling occurred through transcriptional activation of genes responsible for AEA biosynthetic enzymes and CB1 receptor protein.”

Dr. Balapal, who is also a faculty at Department of Psychiatry, College of Physicians and Surgeons, Columbia University, NY, and his colleagues note that AEA/CB1 receptor/pERK1/2 signaling molecules that regulate the formation of proper synaptic connections in the developing brain might be directly responsible for the synaptic and memory deficits associated with FASD.

Dr. Antonio Noronha, director of NIAAA’s Division of Neuroscience and Behavior, believes the study’s findings have important implications for the prevention of FASD.

“Understanding the mechanism leading to the neurodegeneration that underlies the development of FASD is a critical step in developing novel treatments to block alcohol-induced neurotoxicity in the developing brain. Potentially, these data can lead to the development of drugs or other tools that target the endocannabinoid/CB1 receptor-ERK 1/2 signaling pathways, and avoid or reverse brain damages,” said Dr. Noronha.

 

Source: Anandamide–CB1 Receptor Signaling Contributes to Postnatal Ethanol-Induced Neonatal Neurodegeneration, Adult Synaptic, and Memory Deficits. Subbanna, S, et al. J. Neuroscience.