Minocycline treatment effects on cognition, sleep, breathing and body temperature in a model for sporadic Alzheimer's disease

Abstract

AbstractBackgroundChronic inflammation plays an important role in the cascade of molecular events in the brain of patients with Alzheimer's disease (AD). Preclinical studies have shown that minocycline has a potent anti‐inflammatory effect exerted by its neuroprotective action in various neurodegenerative diseases, such as AD. Thus, we tested the hypothesis that minocycline treatment could reverse / minimize the cognitive and respiratory and sleep deficits of our sporadic AD model.MethodWe used as an animal model for sporadic Alzheimer’s disease (AD) induced by icv injection of streptozotocin (STZ) (2 mg/kg). After five consecutive days of daily dosing with minocycline (30 mg / kg, i.p) the animals were submitted to the experiments. We evaluated memory and learning by Barnes' maze (n = 12), ventilatory parameters during sleep and wakefulness by the whole body plethysmography method and sleep time by electroencephalography method. We evaluate body temperature also during all experiments.ResultThe minocycline treatment improved learning and memory of the STZ‐AD model (n = 12, p < 0.05). But it did not decrease the sensitivity of STZ‐AD model to CO2 ventilatory response during wakefulness Placebo (VE mean ± standard deviation: STZ‐AD = 2477.5 ± 514.8 mL. Kg−1. min−1 vs VE Placebo‐Vehicle = 2005.1 ± 364.2 mL. Kg−1. min−1) vs Minocycline (VE Minocycline‐STZ‐AD = 2535.0 ± 246.7 vs VE Minocycline‐Vehicle = 1936.0 ± 226.4 mL. Kg−1. min−1) (P >0.05 test Two‐Way ANOVA). Similarly, minocycline treatment had no effect on reversal of wakefulness increase in STZ‐AD model (% Time spent in awake state mean ± standard deviation: Placebo‐STZ = 66.4 ± 17.7 vs Placebo‐Vehicle = 53.0 ± 9.9 % ) (Minocycline‐STZ = 66.6 ± 8.2 vs Minocycline‐Vehicle = 44.8 ± 11.7 %). No difference was observed in the body temperature of the animals during the experiments, but the hypoxia promoted a regulated fall in body temperature.ConclusionIn summary, our data suggest that minocycline is a promising drug to minimize cognitive dysfunctions in the AD model without changing the respiratory and sleep‐wake cycle parameters.