J Comprehensible Results

Journal of Comprehensible Results

Sanchez E, Bigbee J, Fobbs W, Robinson S, Sato-Bigbee C (2008)
Opioid Addiction and Pregnancy:Perinatal Exposure to Buprenorphine
Affects Myelination in the Developing Brain.
Glia 56:1010-1027

(Translated by Brenna Kent)

Background


Myelin

Myelin forms a sheath around neurons in the brain which helps to increase the speed at which information, in the form of electrical impulses, can travel. Without myelin, neurons tend to be larger and require more energy. For example, the unmyelinated giant axon of the squid has a 500 mm diameter and requires 5,000 times as much energy as a myelinated axon in a frog which is only 12 mm in diameter [2]. When myelin is altered or damaged, motor and sensory function can be affected; multiple sclerosis is one of the best-known diseases in which demyelination plays a role. Currently there is not a cure for demyelinating diseases; instead treatments focus on reducing symptoms [3].

Myelination begins as early as the fifth fetal month or towards the end of the second trimester. Rapid myelination continues till around the second year of life and then continues more gradually into young adulthood [4]. Myelin is composed of proteins and lipids; a few of its major constituents are myelin basic proteins (MBP) and myelin associated glycoprotein (MAG) which are shown in figure 14.

Figure 14: Diagram of Myelin and its Components.The proteins studied in this article are circled in red.
MBP: accounts for approximately 30% of myelin proteins
MAG: accounts for approximately 1% of myelin, but it may have a role in the initiation of myelination[5]

Adapted from "Magnetic resonance imaging of myelin" by Laule, C., Vavasour, I.M., Kolind, S.H. et al., 2007, GLIA, 4, p. 460. Copyright 2007 by Springer New York

 

Oligodendrocytes

In the central nervous system, myelin is produced by cells called oligodendrocytes. Oligodendrocyte formation starts with oligodendrocyte progenitor cells (OPCs) which then go through several stages of development. Throughout their development, oligodendrocytes express opioid receptors which normally bind endogenous opioids, ones that are naturally made in the body [7], such as endorphins like endomorphin 1. However if other opioids are introduced, they have the potential to bind to the opioid receptors on oligodendrocytes which could alter myelination in the developing brain.

 

The stages of oligodendrocyte maturation are shown above on the left. On the right, is a depiction of how oligodendrocytes interact with axons and produce myelin[10].

 

Maintenance Therapy

Because synthetic opioids have the potential to bind to opioid receptors on oligodendrocytes, this has implications for how opioid addiction is treated. Maintenance therapy is one treatment for opioid addiction. In maintenance therapy, opioid addicts are prescribed an opioid like methadone or buprenorphine in order to reduce the risk of relapse and combat the symptoms of withdrawal. Both methadone and buprenorphine work by occupying the same receptors that a prescription opioid or heroin would. However, methadone acts as an opioid agonist and buprenorphine acts as a partial opioid agonist. This means that they do not activate the receptors that they bind to as fully as a prescription opioid would, so there is not a feeling of euphoria that is typically associated with misusing an opioid. Buprenorphine and methadone are also prescribed to pregnant opioid addicts [6]. Although buprenorphine and methadone are intended to bind to the receptors in the brain that control the feeling of pain, they can also bind to the opioid receptors on oligodendrocytes that are described above.