Summary: | Recent hypotheses concerning the pathogenesis of sudden infant death
syndrome (SIDS) have focused on developmental abnormalities of the central
nervous system, which are believed to produce cardiorespiratory instability in
susceptible infants. The present study was designed to investigate developmental
abnormalities in the dorsal motor nucleus of the vagus (DMV) in SIDS.
Using serial histological sections of the brainstem from SIDS cases and agematched
control cases without neurological disease, morphometric analyzes were
performed to compare postnatal changes in 1) the total volume of the DMV, 2) the
numerical density of neurons (Nv, cells per mm³), 3) the total number of neurons,
and 4) mean neuronal profile area. In the SIDS cases there was a significant
increase in the total volume of the DMV (33%), when compared to controls. In SIDS
there was a significant decrease in the Nv of neurons (33%), although the total
number of neurons did not differ significantly from controls. Mean neuronal profile
areas were significantly greater in SIDS for both motor (31&) and non-motor (30%)
neurons, when compared to controls. These changes are consistent with an
overgrowth of the DMV during early postnatal development. Given the role of the
DMV in the autonomic control of breathing and heart rate, this subtle developmental
disorder likely contributes to the cardiorespiratory instability characteristic of
susceptible infants.
Given the possibility that increased expression of insulin-like growth factor
I during early postnatal development might contribute to this overgrowth,
morphometric analyses were performed on the DMV and hypoglossal nucleus (HN)
in transgenic mice, which overexpress IGF-I postnatally, and in normal littermate
controls on postnatal day 35. Morphometric variables included 1) the total volumes
of the DMV and HN, 2) the Nv of neurons, 3) the total number of neurons, and 4) the
mean neuronal profile areas. In transgenic mice there was a significant increase in
the volumes of both the DMV (84%) and the HN (30%). The Nv of neurons was
significantly reduced in both nuclei in transgenic mice. In the DMV, however, there
was a significant increase in the total number of neurons (56%). In the HN, the total
number of neurons did not differ significantly between transgenic mice and controls.
Mean neuronal profile areas were significantly increased in transgenic mice in both
the DMV (35%) and the HN (22%). Available evidence suggests that the increased
neuron number in the DMV results from an antiapoptotic effect of IGF-I.
In a third experiment, morphometric and stereological analyses were
performed in the DMV of rats during normal postnatal development to determine the
time course of the progressive and regressive phases of synaptogenesis. The initial
phase of synapse proliferation occurred from birth to postnatal day 30, while the
regressive phase of synapse elimination occurred after day 30. Recent hypotheses
suggest that SIDS results from a failure to eliminate normally extraneous synapses
from the brainstem. By knowing the age at which peak synaptic densities occur, one
could introduce exogenous growth factors to prevent normal elimination of
synapses. Preventing synapse elimination from the brainstem of the rat might be
expected to produce an animal model of SIDS. (A scientific formula N[subscript V] used in this abstract could not be reproduced by the software.)
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