Prenatal exposure to ultrasound waves impacts neuronal migration in mice

Abstract

Neurons of the cerebral neocortex in mammals, including humans, are generated during fetal life in the proliferative zones and then migrate to their final destinations by following an inside-tooutside sequence. The present study examined the effect of ultrasound waves (USW) on neuronal position within the embryonic cerebral cortex in mice. We used a single BrdU injection to label neurons generated at embryonic day 16 and destined for the superficial cortical layers. Our analysis of over 335 animals reveals that, when exposed to USW for a total of 30 min or longer during the period of their migration, a small but statistically significant number of neurons fail to acquire their proper position and remain scattered within inappropriate cortical layers and͞or in the subjacent white matter. The magnitude of dispersion of labeled neurons was variable but systematically increased with duration of exposure to USW. These results call for a further investigation in larger and slower-developing brains of non-human primates and continued scrutiny of unnecessarily long prenatal ultrasound exposure.brain malformations ͉ cerebral cortex ͉ embryonic development A fundamental feature of cerebral cortical organization is that positions of its neuronal constituents into horizontal (laminar) and vertical (radial) arrays ultimately define their connectivity and function (1). Cortical neurons acquire appropriate positions by migration from the site of their origin in the proliferative zones lining the cerebral ventricle, according to a precise schedule (2, 3) and along well defined pathways (4-6). When the rate of neuronal migration and the sequence of arrival are altered because of genetic and͞or environmental factors, various consequences, including abnormal behavior, have been observed (7-13). In terms of orientation and directionality of movement, neuronal migration to the cerebral cortex can be classified into radial (proceeding radially from the ventricular to the pial surface) (5, 14) and tangential (running parallel to the brain surface) (15)(16)(17). Contact interaction between migrating neurons and the surfaces of neighboring cells plays a decisive role in selecting the migratory pathway and determining their final position (18,19). Neuronal migration involves translocation of the nucleus and the surrounding cytoplasm with the leading process, which requires rearrangement of the cytoskeleton (20, 21). As a consequence of these complex cellular and molecular interactions, the process of neuronal migration is highly sensitive to a variety of biological, physical, and chemical agents, as well as to specific genetic mutations (7-13). For example, repeated exposure of the rodent and primate fetal brain to environmental agents, such as alcohol (9), drugs (22), neurotrophic viruses (23), and ionizing irradiation (24, 25), causes misplacement of neurons and behavioral deficits.To our knowledge, the effect of ultrasound waves (USW) on the rate of migration in the cerebral cortex has never been tested, although it has been reported ...

Our unborn children at risk?

“…In this study, the TI was not provided, but the I SPTA (a measure of thermal effects) and MI were within U.S. Food and Drug Administration limits, although the I SPPA was slightly high. Therefore, thermal and mechanical cavitation effects are unlikely to be the cause of heterotopia; the authors (1) emphasize that the mechanism causing heterotopia is not understood. Other known types of US bioeffects that may be the cause include acoustic streaming, propagation of shear waves resulting in torque, and radiation force (11).…”

“…US is capable of causing deleterious bioeffects to the human fetus, and the paper by Ang et al (1) reminds us of the need to maintain our vigilance. More fundamentally, the study may illustrate a new consequence of US where we have little or no understanding of the mechanism.…”

“…The authors (1) suggest that such neuronal heterotopia may result in anomalies in brain circuitry and synaptic activity. Does this study indicate that we should be concerned about human fetal US?…”

“…T he study by Ang et al (1) in this issue of PNAS strikes a precautionary note, in that it presents experimental evidence that prolonged continuous ultrasound (US) exposure may cause mild disruption in neuronal migration to the cerebral cortex in fetal mice. The authors (1) suggest that such neuronal heterotopia may result in anomalies in brain circuitry and synaptic activity.…”

“…First, we will review the essential details of the study by Ang et al (1). In the mouse, cells of the neocortex are formed and largely complete their migrations from their place of origin in the ventricular zone (VZ) to the cortex during the final week of a 19-day gestation (2).…”