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Published on: August 2, 2017
The correlation between microtubule-associated protein 2 in the brainstem of SIDS victims and physiological data on
Toshiko Sawaguchi1, Franco Patricia, Hazim Kadhim
1Department of Legal Medicine,Tokyo Women's Medical University School of Medicine, 8-1 Kawada-cho, Shinjuku, Tokyo 162-8666, Japan. tsawagu@research.twmu.ac.jp
Background:
Microtubule-associated protein 2(MAP2), a cytoskeletal protein of the neuron, is a marker of early ischemic neuronal damage. As a chronic hypoxic situation exists in the brains of victims of the sudden infant death syndrome (SIDS), the correlation between MAP2-positive neurons or dendritic spines in the brainstem and sleep apnea was investigated in SIDS, which is still the main cause of postneonatal infant death.
Materials And Methods:
27,000 infants were studied prospectively to characterize their sleep-wake behavior and amongst these, 38 infants died under 6 months of age. They included 26 cases of SIDS. The frequency and duration of sleep apneae were analyzed. The brainstem material was collected and immunohistochemistry of MAP2 was carried out. The density of MAP2-positive neurons, dendrites and dendritic spines were measured quantitatively. Correlation analyses were carried out between the MAP2-associated pathological data and the physiological data of sleep apnea.
Results:
One negative correlation between the density of MAP2-positive dendrites in the pars compacta of pedunculo-pontine tegmentum nucleus (PPTNc) and the duration of obstructive apnea (p=0.017) and two SIDS-specific positive correlations between the density of MAP2-positive dendrites in the pars dissipata of pedunculo-pontine tegmentum nucleus (PPTNd) and the duration of central apnea (p=0.005) and between the dorsal raphe and the frequency of obstructive apnea were found in SIDS victims. The density of MAP2-positive dendritic spines in PPTNc was significantly higher in SIDS than in control (p=0.034).
Conclusions:
The significant correlations with the MAP2-positive findings in the midbrain arousal pathway and the characteristics of sleep apnea in SIDS victims were in agreement with the association with apnea and arousal-deficiency in SIDS.
Insights
Sudden Infant Death Syndrome (SIDS) victims with sleep apnea showed altered Microtubule-associated protein 2 (MAP2) levels in brainstem regions critical for arousal. These findings link MAP2 changes to sleep apnea characteristics in SIDS.
Area of Science:
- Neuroscience
- Pathology
- Pediatrics
Background:
- Microtubule-associated protein 2 (MAP2) is a neuronal cytoskeletal protein indicating early ischemic damage.
- Chronic hypoxia in Sudden Infant Death Syndrome (SIDS) brains suggests a link between MAP2 and sleep apnea.
Purpose of the Study:
- To investigate the correlation between MAP2-positive neurons/dendritic spines in the brainstem and sleep apnea in SIDS victims.
- To explore MAP2 as a potential biomarker for SIDS and its association with sleep-disordered breathing.
Main Methods:
- Prospective study of 27,000 infants, analyzing sleep-wake behavior.
- Postmortem brainstem analysis of 38 infant deaths (26 SIDS) using MAP2 immunohistochemistry.
- Quantitative measurement of MAP2-positive neurons, dendrites, and spines, correlated with sleep apnea data.
Main Results:
- Negative correlation found between MAP2-positive dendrites in the PPTNc and obstructive apnea duration.
- Positive correlations observed between MAP2-positive dendrites in the PPTNd and central apnea duration, and in the dorsal raphe with obstructive apnea frequency.
- Increased MAP2-positive dendritic spines in the PPTNc of SIDS victims compared to controls.
Conclusions:
- Significant correlations exist between MAP2 findings in the midbrain arousal pathway and sleep apnea characteristics in SIDS.
- These findings support the association of apnea and arousal deficiency in SIDS.
- MAP2 may serve as a marker for neuronal changes related to sleep-disordered breathing in SIDS.
