Alcohol and the Developing Brain : Neuroanatomical Studies, Part 2

by National Institute of Health

(Page 3 of 4)

Fewer Dendritic Spines

Proper CNS communication depends on an adequate number of dendritic spines and dendritic branching, because dendrites are the sites of contact for neurons. Animal studies, both in vivo and in vitro, have demonstrated that developmental alcohol exposure negatively affects the structural integrity of the dendrites and the number of dendritic spines in neurons located in the substantia nigra (a group of nerve cells involved in movement), the cortex, and the hippocampus. For example, Tarelo-Acuna and colleagues showed that prenatal and postnatal alcohol exposure alters the proportions of different spine shapes in the long (apical) dendrites of hippocampal CA1 pyramidal cells.

Changes in the dendritic morphology and reductions in dendritic spines in the hippocampus interfere with the optimal transmission of the neural impulse. Relating these data to humans, it is possible that these changes could contribute to the cognitive problems seen in children with FAS, because the hippocampus is involved in learning and memory.

Disrupted Mitochondrial Membrane

The mitochondria are subcellular structures that produce energy for the cell. Changes in the structural integrity of the mitochondrial membrane and its associated proteins have been shown to initiate apoptosis or necrosis, two possible forms of cell death. Ramachandran demonstrated that alcohol exposure in utero significantly elevates cytochrome c and apoptosis-inducing factor (AIF) levels in mitochondria in the fetal rat brain. Light and colleagues showed that 1 day of alcohol exposure leads to apoptotic Purkinje cells in early generated cerebellar lobules. The observation of these apoptotic neurons coincides with the release of cytochrome c from the mitochondria of the Purkinje cells. These studies suggest that alcohol-induced neuronal loss may occur via disruption of mitochondria within those neurons.

Changes in Cell Adhesion Molecule Properties

The extracellular matrix (ECM), a filamentlike structure on the surface of the cell, is crucial for proper adhesion, migration, and differentiation of neurons in the developing CNS. Therefore, disruptions in the ECM can have severe negative ramifications for developing neurons. One such disruption of the ECM is evident in alcohol's effects on the L1 cell adhesion molecule (L1CAM), a cell surface protein that promotes cell-to-cell binding. Charness and coworkers demonstrated that alcohol inhibits the adhesive properties of L1CAM in cell cultures, preventing neurons from properly adhering to each other or to the ECM. Bearer and colleagues reported that alcohol inhibited L1CAM-mediated outgrowth of the connective fibers from early postnatal rat cerebellar neurons. Collectively, these results suggest that developmental alcohol exposure may alter cellular components, such as L1CAM, and that the consequences of a change in L1CAM function could be detrimental to brain development.

Neural Circuitry Modifications

A complete, intact, and functional neural circuitry requires proper connections between regions of the brain. Developmental alcohol exposure has been shown to cause aberrant wiring patterns or abnormalities in fiber bundles in the developing brain. For instance, the size of the corpus callosum, one of the largest fiber bundles in the brain, is significantly reduced following prenatal alcohol exposure in rats. Further research has shown that, in rats, in utero alcohol exposure alters the distribution of neurons from cortical areas projecting through the corpus callosum into the somatosensory cortex, which receives tactile information from the body. Recently, Elberger and associates found that alcohol exposure during the period equivalent to the second trimester in rats resulted in an abnormal dendritic branching of corpus callosal projection neurons in the visual cortex. These findings demonstrate that the interhemispheric connections are affected by prenatal alcohol exposure. Furthermore, early findings indicated that the topographic organization of hippocampal mossy fibers (neuron extensions that terminate in mosslike branchings) was affected by developmental alcohol exposure.

Prenatal alcohol exposure also may significantly interrupt the development of the cortical circuitry by interfering with the proliferation and migration of the cortical neurons. Miller demonstrated that prenatal alcohol exposure delays the migration of neurons from the zone where they are produced to their final destinations, and the rate of migration of these cortical neurons was decreased as well. Such errors in proliferation and migration disrupt synchronized developmental events, which results in ectopic clusters of cortical neurons and abnormal neuronal circuitry. In sum, because of the critical role of integrated neural circuits within the brain, it is obvious that abnormalities in any component of a neuroanatomical circuit resulting from developmental alcohol exposure would have severe consequences for CNS functions.

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