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Neuroanatomical and functional alterations of the respiratory system during sleep and wakefulness in an experimental model for Alzheimer's disease


The dysfunction of the respiratory system is seen in several neurodegenerative diseases such as Alzheimer's, but how the pathophysiology mechanisms of the disease are related with the respiratory system remain poorly documented. Current clinical criteria for diagnosing AD (Alzheimer's Disease) are mainly focused on cognitive deficits produced by dysfunctions of hippocampal and neocortical areas, while non-cognitive symptoms, such as disorders in the sleep or in the respiratory system are neglected and may precede dementia. Alzheimer's Disease (AD), the most common among neurodegenerative disorders frequently associated with age, is characterized by severe brain degeneration, progressive cognitive decline and presence of hyperphosphorylated Tau neurofibrillary tangles (NFTs) and beta-amyloid plaques (A²). Tau protein is a phosphoprotein that has the function of stabilizing microtubules, its activity is regulated by its phosphorylation kinetics. In brain of patients with AD, Tau protein is found in neurofibrillary tangles (NFTs) formed of hyperphosphorylated Tau, indicating failure in the phosphorylation processes. The neurodegeneration in AD occurs in multiple brain regions including hippocampus, cortex, amygdala, neocortex, subcortical regions and regions involved in central chemosensitivity and maintenance of wakefulness, as locus coeruleus, dorsal raphe and the hypothalamus. Recent studies emphasize the possibility of early involvement of the brainstem in AD, where there are the main regions involved in the control of breathing, so that the dysfunction of the region could precede the dementia stage (cognitive decline) in AD. However, the role of these regions in this disease is not well studied. Thus, this project will test the hypothesis that neurochemical changes in AD promote respiratory problems and these problems may precede cognitive decline. The study will be conducted in an animal model of sporadic AD induced by intracerebroventricular injection of streptozotocin (STZ). In this way, changes in the respiratory system will be evaluated in the progression of AD (18 and 36 days after icv injection of STZ) during sleep and wakefulness. (AU)

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Scientific publications (7)
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
VICENTE, MARIANE C.; STABILE, ANGELITA M.; AMORIM, MATEUS; ANIBAL SILVA, CONCEICAO E.; PATRONE, LUIS GUSTAVO A.; CUNHA, THIAGO M.; BICEGO, KENIA C.; ALMEIDA, MARIA C.; CARRETTIERO, DANIEL C.; GARGAGLIONI, LUCIANE H.. Inhibition of Pro-Inflammatory Microglia with Minocycline Improves Cognitive and Sleep-Wake Dysfunction Under Respiratory Stress in a Sporadic Model for Alzheimer's Disease. JOURNAL OF ALZHEIMER'S DISEASE, v. 95, n. 1, p. 21-pg., . (16/04412-0, 16/24577-3)
LONGHINI, LEONARDO S.; PORTO, LAYS S.; ROCHA, ALINE C. G.; BICEGO, KENIA C.; KLEIN, WILFRIED; GARGAGLIONI, LUCIANE H.. Seasonal variation of hypoxic and hypercarbic ventilatory responses in the lizard Tropidurus torquatus. COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY A-MOLECULAR & INTEGRATIVE PHYSIOLOGY, v. 237, . (11/02008-3, 18/01899-0, 16/24577-3)
VICENTE, MARIANE C.; ALMEIDA, MARIA C.; BICEGO, KENIA C.; CARRETTIERO, DANIEL C.; GARGAGLIONI, LUCIANE H.. Hypercapnic and Hypoxic Respiratory Response During Wakefulness and Sleep in a Streptozotocin Model of Alzheimer's Disease in Rats. JOURNAL OF ALZHEIMER'S DISEASE, v. 65, n. 4, p. 1159-1174, . (15/02991-0, 16/24577-3, 15/23426-9)
PATRONE, LUIS GUSTAVO A.; CAPALBO, ARETUZA C.; MARQUES, DANUZIA A.; BICEGO, KENIA C.; GARGAGLIONI, LUCIANE H.. An age- and sex-dependent role of catecholaminergic neurons in the control of breathing and hypoxic chemoreflex during postnatal development. Brain Research, v. 1726, . (15/04849-6, 16/24577-3)
PATRONE, LUIS GUSTAVO A.; DUARTE, JAIME B.; BICEGO, KENIA CARDOSO; STEINER, ALEXANDRE A.; ROMANOVSKY, ANDREJ A.; GARGAGLIONI, LUCIANE H.. TRPV1 Inhibits the Ventilatory Response to Hypoxia in Adult Rats, but Not the CO2-Drive to Breathe. PHARMACEUTICALS, v. 12, n. 1, . (16/24577-3, 15/24785-2, 17/05318-0)
PATRONE, LUIS GUSTAVO A.; BIANCARDI, VIVIAN; MARQUES, DANUZIA A.; BICEGO, KENIA C.; GARGAGLIONI, LUCIANE H.. Brainstem catecholaminergic neurones and breathing control during postnatal development in male and female rats. JOURNAL OF PHYSIOLOGY-LONDON, v. 596, n. 15, p. 3299-3325, . (16/24577-3)

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