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Blunted respiratory responses in the STZ‐induced rat model of Alzheimer's disease
Author(s) -
Ebel Dalton Louis,
Torkilsen Christopher G,
Ostrowski Tim Daniel
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.1072.5
Subject(s) - astrogliosis , medicine , respiratory system , ventilation (architecture) , endocrinology , hippocampus , alzheimer's disease , hypercapnia , central nervous system , neuroscience , anesthesia , biology , disease , mechanical engineering , engineering
Alzheimer's disease (AD) is a debilitating disease of the central nervous system that results in a drastic decline in cognition and memory. In addition, respiratory dysfunction is frequently observed in AD patients, as shown by altered breathing during sleep and blunted minute ventilation during heightened oxygen demand with peak exercise. The combination of AD symptoms leads to a decrease in day‐to‐day function and increased mortality. At this time, the mechanisms behind the respiratory alterations are widely unknown. For this study, an AD rat model was induced by injecting 1.5 mg/kg Streptozotocin (STZ) in the lateral ventricle to trigger pathological changes consistent with sporadic AD. We used plethysmography to analyze the peripheral and central chemoreflex in response to hypoxia (14 ‐ 8% O 2 , equilibrated with N 2 ) or hypercapnia (5% CO 2 , equilibrated with O 2 ), respectively. We compared respiratory parameters before and after injection of STZ or vehicle (aCSF). Morphological changes in the brainstem and hippocampus were immunohistochemically analyzed using an antibody against S‐100B for astrocytes. Similar to the inflammation in the CNS of AD patients, microinjection of STZ induced astrogliosis in the CA1 region of the hippocampus. We also found reactive astrocytes in the commissural part of the nucleus tractus solitarii, an important center for the control of respiration and responses to low oxygen conditions. In comparison, astrocytes in the pre‐Bötzinger complex of AD rats did not change. Analyzing the respiratory pattern, we found an expected age‐dependent decrease in minute ventilation in our control group. This age‐dependent decrease was absent in the AD group, indicating elevated minute ventilation following STZ administration. Peripheral chemoreflex activation with hypoxia showed significant alterations in the AD group, as observed by a blunted elevation of respiratory rate and minute ventilation. Central chemoreflex activation with hypercapnia only decreased respiratory rate following STZ. We show that the STZ‐induced AD rat model displays significant respiratory dysfunction at rest and in response to hypoxia. Thus, this study provides the first model to elucidate the mechanisms behind respiratory dysfunction of sporadic Alzheimer's disease.