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Progression of Chemoreflex (Dys−)function in the Streptozotocin‐Induced Rat Model for Alzheimer’s Disease

2020; Wiley; Volume: 34; Issue: S1 Linguagem: Inglês

10.1096/fasebj.2020.34.s1.09426

1530-6860

Mahima Thapa, Mansi Trivedi, Tim D. Ostrowski,

Sleep and related disorders

Alzheimer’s disease (AD) is associated with gradual memory decline and impairment of cognitive ability. The majority of AD patients also suffer from multiple apneas during sleep. The sleep‐disordered breathing entails a reduced ability to adjust respiration during low oxygen (hypoxia) and/or increased carbon dioxide (hypercapnia) conditions, indicating dysfunction of the respiratory system. In this study, we measured respiratory responses of the Streptozotocin (STZ) ‐induced rat model of AD to hypoxia (10% O 2 ‐ peripheral chemoreflex) and hypercapnia (7% CO 2 ‐ central chemoreflex). Measurements were taken at three weeks (early stage) and three months (late stage) following STZ injection into the lateral ventricles of the brain (2 mg/kg STZ; 6‐week‐old rats, N = 6/group). Three weeks following AD induction, hypoxic exposure increased respiratory rate (RR) of vehicle control (CTL) and STZ‐AD rats. However, this increase was significantly blunted by ~25% in STZ‐AD. The blunted response was partial compensation by increased tidal volume (TV) resulting in a non‐significant decrease of minute ventilation (MV; RR x TV). Three months following AD induction, STZ‐AD rats still had a blunted response of RR to hypoxia, which was similar in magnitude to that observed at 3 weeks. However, at this late time point, baseline RR and MV at normoxia (21% O 2 ) appeared higher in STZ‐AD than those in CTL. Comparing data between time points (3 weeks AD vs. 3 months AD), both groups showed the expected age‐dependent increase in TV and decrease of RR. This decrease in RR was less in STZ‐AD than that in CTL, but the increase in TV was similar in both groups. Thus, STZ‐AD rats had a ~15% higher MV at the 3 months’ time point than at 3 weeks. CTL rats, on the other hand, had similar MV at both ages (~0% change). With exposure to 7% CO 2 , responses for RR, TV, and MV at 3 weeks were similar between CTL and STZ‐AD rats. Also at 3 months responses did not differ between groups. However, within the STZ‐AD group, MV at 3 months was significantly greater in response to hypercapnia than that at the younger age. This increase was due to the absent age‐dependent drop of RR in STZ‐AD. CTL rats, in contrast, had significantly reduced RR at 3 months, leading to comparable MV at both ages. In summary, major changes were observed in the peripheral chemoreflex of STZ‐AD rats throughout our 3‐months observation period. Both, responses to hypoxia (short‐term) and baseline values of respiration under normoxia (long‐term) were altered in these animals. Central chemoreflex function, on the other hand, remained largely unaltered. Support or Funding Information Conference Travel Scholarship by Truman State University to M Thapa and seed money from A.T. Still University to TDO