Perinatal inflammation and gestational intermittent hypoxia disturbs respiratory rhythm generation and long-term facilitation in vitro: Partial protection by acute minocycline.

Perinatal inflammation triggers breathing disturbances early in life and affects the respiratory adaptations to challenging conditions, including the generation of amplitude long-term facilitation (LTF) by acute intermittent hypoxia (AIH). Some of these effects can be avoided by anti-inflammatory treatments like minocycline. Since little is known about the effects of perinatal inflammation on the inspiratory rhythm generator, located in the preBötzinger complex (preBötC), we tested the impact of acute lipopolysaccharide (LPS) systemic administration (sLPS), as well as gestational LPS (gLPS) and gestational chronic IH (gCIH), on respiratory rhythm generation and its long-term response to AIH in a brainstem slice preparation from neonatal mice. We also evaluated whether acute minocycline administration could influence these effects. We found that perinatal inflammation induced by sLPS or gLPS, as well as gCIH, modulate the frequency, signal-to-noise ratio and/or amplitude (and their regularity) of the respiratory rhythm recorded from the preBötC in the brainstem slice. Moreover, all these perinatal conditions inhibited frequency LTF and amplitude long-term depression (LTD); gCIH even induced frequency LTD of the respiratory rhythm after AIH. Some of these alterations were not observed in slices pre-treated in vitro with minocycline, when compared with slices obtained from naïve pups, suggesting that ongoing inflammatory conditions affect respiratory rhythm generation and its plasticity. Thus, it is likely that alterations in the inspiratory rhythm generator and its adaptive responses could contribute to the respiratory disturbances observed in neonates that suffered from perinatal inflammatory challenges.

Chronic intermittent hypoxia alters main olfactory bulb activity and olfaction.

Olfactory dysfunction is commonly observed in patients with obstructive sleep apnea (OSA), which is related to chronic intermittent hypoxia (CIH). OSA patients exhibit alterations in discrimination, identification and odor detection threshold. These olfactory functions strongly rely on neuronal processing within the main olfactory bulb (MOB). However, a direct evaluation of the effects of controlled CIH on olfaction and MOB network activity has not been performed. Here, we used electrophysiological field recordings in vivo to evaluate the effects of 21-day-long CIH on MOB network activity and its response to odors. In addition, we assessed animals´ olfaction with the buried food and habituation/dishabituation tests. We found that mice exposed to CIH show alterations in MOB spontaneous activity in vivo, consisting of a reduction in beta and gamma frequency bands power along with an increase in the theta band power. Likewise, the MOB was less responsive to odor stimulation, since the proportional increase of the power of its population activity in response to four different odorants was smaller than the one observed in control animals. These CIH-induced MOB functional alterations correlate with a reduction in the ability to detect, habituate and discriminate olfactory stimuli. Our findings indicate that CIH generates alterations in the MOB neural network, which could be involved in the olfactory deterioration in patients with OSA.

Bioactive Food Abates Metabolic and Synaptic Alterations by Modulation of Gut Microbiota in a Mouse Model of Alzheimer's Disease.

Recent investigations have demonstrated an important role of gut microbiota (GM) in the pathogenesis of Alzheimer's disease (AD). GM modulates a host's health and disease by production of several substances, including lipopolysaccharides (LPS) and short-chain fatty acids (SCFAs), among others. Diet can modify the composition and diversity of GM, and ingestion of a healthy diet has been suggested to lower the risk to develop AD. We have previously shown that bioactive food (BF) ingestion can abate neuroinflammation and oxidative stress and improve cognition in obese rats, effects associated with GM composition. Therefore, BF can impact the gut-brain axis and improved behavior. In this study, we aim to explore if inclusion of BF in the diet may impact central pathological markers of AD by modulation of the GM. Triple transgenic 3xTg-AD (TG) female mice were fed a combination of dried nopal, soy, chia oil, and turmeric for 7 months. We found that BF ingestion improved cognition and reduced Aß aggregates and tau hyperphosphorylation. In addition, BF decreased MDA levels, astrocyte and microglial activation, PSD-95, synaptophysin, GluR1 and ARC protein levels in TG mice. Furthermore, TG mice fed BF showed increased levels of pGSK-3ß. GM analysis revealed that pro-inflammatory bacteria were more abundant in TG mice compared to wild-type, while BF ingestion was able to restore the GM's composition, LPS, and propionate levels to control values. Therefore, the neuroprotective effects of BF may be mediated, in part, by modulation of GM and the release of neurotoxic substances that alter brain function.