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Impaired Chemoreflex Response to Acute Hypoxia Correlates with Decreased Activation of the Medial Nucleus Tractus Solitarii in the STZ‐Induced Rat Model of Alzheimer's Disease
Author(s) -
Brown Andrea G.,
Thapa Mahima,
Hooker John W.,
Ostrowski Tim D.
Publication year - 2018
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.2018.32.1_supplement.545.3
Subject(s) - hypoxia (environmental) , streptozotocin , endocrinology , medicine , brainstem , forebrain , anesthesia , central nervous system , diabetes mellitus , chemistry , organic chemistry , oxygen
Background Alzheimer's disease (AD) is the most common cause of dementia and clinically diagnosed largely based on cognitive decline. Most AD patients also present with disorders of respiration, swallowing, and autonomic function. Current studies suggest that pathological changes in the brainstem manifest simultaneously or even before those in forebrain regions, and may account for non‐cognitive symptoms. Identifying the pathologic changes in brainstem centers may elucidate the mechanisms behind cardiorespiratory dysfunction in AD. This study concentrated on the respiratory deficits. Using the streptozotocin (STZ)‐induced model of AD, we determined cell activation in response to acute hypoxia in the nucleus tractus solitarii (nTS), a brainstem area that is integral for chemoreflex function. Methods Sporadic AD was induced in Sprague Dawley rats (280 ± 17g, n = 6 rats/group) by intracerebroventricular injections of streptozotocin (1.5 mg/kg STZ in citrate buffer; day 1 and 3). Vehicle injections served as control (CTL). Peripheral chemoreflex function was tested with two hours of acute hypoxia (10% O 2 ) in a plethysmography chamber. Immediately following the hypoxic period, the brains were fixed with 4% paraformaldehyde. Four representative areas of the nTS were immunohistochemically analyzed for cell activation (c‐Fos). Results The chemoreflex‐mediated increase of minute ventilation in response to acute hypoxia was significantly blunted by ~20% in STZ rats when compared to CTL ( p = 0.03). The diminished response continued over the entire 2 hours of hypoxia and was mainly due to alterations in respiratory rate. Immunohistochemical analysis revealed a ~25% decrease of hypoxia‐mediated cell activation in the medial nTS of STZ rats (−14.04 mm from bregma, p = 0.02). This decline in cell activation was not due to a general decrease in cell density as shown by DAPI staining. The level of activation in commissural and rostral nTS sections was not different from CTL. Conclusion We had previously found respiratory dysregulation in the STZ model of sporadic AD. This follow‐up study analyzed respiratory parameters over a two‐hour hypoxic period and the underlying pattern of cell activation in the nTS. Our data document a reduced activation of the medial nTS in the chemoreflex pathway of AD rats. This finding may help explain the respiratory symptoms observed in AD patients. This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .