Amyloid Beta Inhibits Olfactory Bulb Activity and the Ability to Smell

Abstract

Early olfactory dysfunction has been consistently reported in both Alzheimer’s disease (AD) and in transgenic mice that reproduce some features of this disease. In AD transgenic mice, alteration in olfaction has been associated with increased levels of soluble amyloid beta protein (Aβ) as well as with alterations in the oscillatory network activity recorded in the olfactory bulb (OB) and in the piriform cortex. However, since AD is a multifactorial disease and transgenic mice suffer a variety of adaptive changes, it is still unknown if soluble Aβ, by itself, is responsible for OB dysfunction both at electrophysiological and behavioral levels. Thus, here we tested whether or not Aβ directly affects OB network activity in vitro in slices obtained from mice and rats and if it affects olfactory ability in these rodents. Our results show that Aβ decreases, in a concentration- and time-dependent manner, the network activity of OB slices at clinically relevant concentrations (low nM) and in a reversible manner. Moreover, we found that intrabulbar injection of Aβ decreases the olfactory ability of rodents two weeks after application, an effect that is not related to alterations in motor performance or motivation to seek food and that correlates with the presence of Aβ deposits. Our results indicate that Aβ disrupts, at clinically relevant concentrations, the network activity of the OB in vitro and can trigger a disruption in olfaction. These findings open the possibility of exploring the cellular mechanisms involved in early pathological AD as an approach to reduce or halt its progress.

Amyloid β Peptide-Induced Changes in Prefrontal Cortex Activity and Its Response to Hippocampal Input

“…Our finding that A β inhibits PFC spontaneous network activity is very similar to observations by our group and others that direct application of A β inhibits spontaneous network activity in a variety of networks including the olfactory bulb [43], the entorhinal cortex [44], and the hippocampus [37, 45]. In fact, a previous finding already indicated that direct application of A β inhibits synchronized activity induced by calcium depletion in PFC slices [46].…”

Selenomethionine Ameliorates Neuropathology in the Olfactory Bulb of a Triple Transgenic Mouse Model of Alzheimer’s Disease

“…Aβ oligomers have a major role in the neurotoxic pathology of AD. A strong correlation also has been suggested between the accumulation of soluble Aβ in the OB and very early olfactory (including OB activity) dysfunction in both AD patients and transgenic mice [1,29]. Conversely, a reduced level of Aβ ameliorated the olfactory dysfunction observed in AD transgenic mice [27].…”

The olfactory dysfunctions occurring in the course of Alzheimer’s disease

“…It is worth mentioning that research involving mice has shown that amyloid accumulating in the olfactory bulb inhibits its electrical activity, which oscillation amplitude is proportional to the smell task difficulty level [45]. In humans, olfactory bulb is a region, wherein occurs one of the earliest neuropathological alterations due to AD and its damage is common in this disease.…”

“…Warto wspomnieć, że badania na myszach wykazują, iż kumulujący się w opuszce węchowej amyloid hamuje jej aktywność elektryczną, której amplituda oscylacji jest wprost proporcjonalna do trudności zadania węchowe-go [45]. U ludzi opuszka węchowa jest rejonem, gdzie pojawiają się jedne z najwcześniejszych zmian neuropatologicznych związanych z AD; jej uszkodzenie jest powszechne w tej chorobie.…”