Capsaicin evoked cardiopulmonary reflexes and heart rate variability responses are attenuated in a rat model of dementia induced by streptozotocin

Alzheimer's dementia (AD) principally a degenerative ailment of nervous system, also impacts systemic functions, including cardiopulmonary (CP) dynamics. Capsaicin-induced nociceptive CP reflexes play a defensive role against infective and inflammatory pathologies, yet their modulation in preclinical (early-stage) AD remains unclear. Therefore, this study investigates the modulation of capsaicin-evoked protective CP reflexes in streptozotocin-induced preclinical AD rat models as compared to Sham rats. Twelve adult Wistar male rats were assigned to AD and Sham groups, wherein preclinical AD was induced via bilateral intracerebroventricular streptozotocin injections using stereotaxic coordinates. Jugular vein cannulation enabled administration of capsaicin to evoke the nociceptive reflex CP responses, while femoral artery cannulation allowed continuous recording of blood pressure. Lead II electrocardiogram and breathing movements were also recorded. Hippocampal sections were stained with cresyl violet to evaluate neuronal cytoarchitecture, to confirm the induction of preclinical AD. Capsaicin evoked immediate hypotension, hyperventilation, tachypnea, and bradycardia in both AD and Sham groups, but were significantly attenuated (mean arterial pressure from 28 to 11%; respiratory rate from 44 to 15%; minute ventilation from 201 to 28%; heart rate from 30 to 7% of baseline) in AD rats. In addition, capsaicin-evoked heart rate variability alterations were significantly attenuated in the AD rats. Immunofluorescence analysis demonstrated amyloid β and phosphorylated Tau proteins deposition in the paraventricular nucleus of hypothalamus as well as key brainstem autonomic nuclei. To conclude, diminished nociceptive CP reflex responses in preclinical AD may be associated with AD-related pathologies in hypothalamus and brainstem, harboring the CP autonomic regulatory centers.