Hypomyelination, memory impairment, and blood-brain barrier permeability in a model of sleep apnea
Lenise Jihe Kim1, Denis Martinez1, Cintia Zappe Fiori1
1Laboratório Interdisciplinar de Pesquisa em Sono (LIPES-UFRGS), Serviço de Cardiologia, Universidade Federal do Rio Grande do Sul (UFRGS), Hospital de Clínicas de Porto Alegre (HCPA), Ramiro Barcelos, 2350, 90035-903 Porto Alegre, RS, Brazil.
Abstract:
We investigated the effect of intermittent hypoxia, mimicking sleep apnea, on axonal integrity, blood-brain barrier permeability, and cognitive function of mice. Forty-seven C57BL mice were exposed to intermittent or sham hypoxia, alternating 30s of progressive hypoxia and 30s of reoxigenation, during 8h/day. The axonal integrity in cerebellum was evaluated by transmission electron microscopy. Short- and long-term memories were assessed by novel object recognition test. The levels of endothelin-1 were measured by ELISA. Blood-brain barrier permeability was quantified by Evans Blue dye. After 14 days, animals exposed to intermittent hypoxia showed hypomyelination in cerebellum white matter and higher serum levels of endothelin-1. The short and long-term memories in novel object recognition test was impaired in the group exposed to intermittent hypoxia as compared to controls. Blood-brain barrier permeability was similar between the groups. These results indicated that hypomyelination and impairment of short- and long-term working memories occurred in C57BL mice after 14 days of intermittent hypoxia mimicking sleep apnea.
Insights
Intermittent hypoxia, mimicking sleep apnea, caused hypomyelination and impaired short- and long-term memory in mice. Blood-brain barrier permeability remained unaffected by this exposure.
Area of Science:
- Neuroscience
- Sleep Medicine
- Toxicology
Background:
- Sleep apnea is linked to neurological deficits.
- Intermittent hypoxia (IH) is a key feature of sleep apnea.
- The impact of IH on brain structure and function requires further investigation.
Purpose of the Study:
- To investigate the effects of IH on axonal integrity, blood-brain barrier (BBB) permeability, and cognitive function in mice.
- To elucidate the neuropathological consequences of IH mimicking sleep apnea.
Main Methods:
- Forty-seven C57BL mice were subjected to IH (alternating hypoxia and reoxygenation) or sham conditions for 8 hours daily over 14 days.
- Axonal integrity was assessed using transmission electron microscopy.
- Cognitive function was evaluated via the novel object recognition test.
- Blood-brain barrier permeability was measured using Evans Blue dye, and endothelin-1 levels were quantified via ELISA.
Main Results:
- Mice exposed to IH exhibited hypomyelination in cerebellar white matter.
- Serum levels of endothelin-1 were significantly elevated in the IH group.
- Impairment in both short- and long-term memory was observed in the IH group compared to controls.
- No significant difference in BBB permeability was found between IH and sham groups.
Conclusions:
- Fourteen days of IH, simulating sleep apnea, induces hypomyelination in the cerebellum.
- IH exposure leads to cognitive deficits, specifically impairing short- and long-term working memory.
- Endothelin-1 may play a role in the observed neuropathological changes, while BBB integrity appears preserved.
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