Hypercapnic and Hypoxic Respiratory Response During Wakefulness and Sleep in a Streptozotocin Model of Alzheimer's Disease in Rats

Author(s)

Vicente, Mariane C. ^[1] ; Almeida, Maria C. ^[2] ; Bicego, Kenia C. ^[1] ; Carrettiero, Daniel C. ^[2] ; Gargaglioni, Luciane H. ^[1]

Affiliation

^[1] Sao Paulo State Univ UNESP FCAV, Dept Anim Morphol & Physiol, Jaboticabal, SP - Brazil

^[2] UFABC, Ctr Nat & Human Sci, Sao Bernardo Do Campo, SP - Brazil

• Document type: Journal article
• Source: JOURNAL OF ALZHEIMER'S DISEASE; v. 65, n. 4, p. 1159-1174, 2018.
• Web of Science Citations: 1

Abstract

Besides the typical cognitive decline, patients with Alzheimer's disease (AD) develop disorders of the respiratory system, such as sleep apnea, shortness of breath, and arrhythmias. These symptoms are aggravated with the progression of the disease. However, the cause and nature of these disturbances are not well understood. Here, we treated animals with intracerebroventricular streptozotocin (STZ, 2 mg/kg), a drug that has been described to cause Alzheimer-like behavioral and histopathological impairments. We measured ventilation ((V) over dot(E)), electroencephalography, and electromyography during normocapnia, hypercapnia, and hypoxia in Wistar rats. In addition, we performed western blot analyses for phosphorylated tau, total tau, and amyloid-beta (A beta) peptide in the locus coeruleus (LC), retrotrapezoid nucleus, medullary raphe, pre-Botzinger/Botzinger complex, and hippocampus, and evaluated memory and learning acquisition using the Barnes maze. STZ treatment promoted memory and learning deficits and increased the percentage of total wakefulness during normocapnia and hypercapnia due to a reduction in the length of episodes of wakefulness. CO2-drive to breathe during wakefulness was increased by 26% in STZ-treated rats due to an enhanced tidal volume, but no changes in (V) over dot(E) were observed in room air or hypoxic conditions. The STZ group also showed a 70% increase of A beta in the LC and no change in tau protein phosphorylation. In addition, no alteration in body temperature was observed. Our findings suggest that AD animals present an increased sensitivity to CO2 during wakefulness, enhanced A beta in the LC, and sleep disruption. (AU)

• FAPESP's process: 15/02991-0 - Involvement of TRPM8 channels in thermoregulation of Wistar rats
• Grantee: Maria Camila Almeida
• Support Opportunities: Regular Research Grants
• FAPESP's process: 16/24577-3 - Neuroanatomical and functional alterations of the respiratory system during sleep and wakefulness in an experimental model for Alzheimer's disease
• Grantee: Luciane Helena Gargaglioni Batalhão
• Support Opportunities: Regular Research Grants
• FAPESP's process: 15/23426-9 - Beta-amyloid in Alzheimer's Disease: death or survival? Involvement of NF-kappaB and BAG2
• Grantee: Daniel Carneiro Carrettiero
• Support Opportunities: Regular Research Grants