Abstract
Reversible formation of PHF-like phosphorylated tau, an early feature of Alzheimer’s disease (AD) was previously shown to occur in torpor during hibernation in the Golden hamster (Syrian hamster, Mesocricetus auratus). Here, we tackled the question to what extent hibernating Golden hamsters can serve as a model for the early stage of AD. During early AD, anosmia, the loss of olfactory function, is a common and typical feature. We, thus, investigated tau phosphorylation, synaptic plasticity and behavioral physiology of the olfactory system during hibernation. Tau was phosphorylated on several AD-relevant epitopes, and distribution of PHF-like phosphorylated tau in the olfactory bulb was quite similar to what is seen in AD. Tau phosphorylation was not associated with a destabilization of microtubules and did not lead to fibril formation. Previously, we observed a transient spine reduction in pyramidal cells in the hippocampus, which is correlated with the distribution of phosphorylated tau. Here we show that granule cells in the olfactory bulb are devoid of phosphorylated tau and maintain their spines number during torpor. No reduction of synaptic proteins was observed. However, hibernation did impair the recall performance in a two-odor discrimination task. We conclude that hibernation is associated with a specific olfactory memory deficit, which might not be attributed to the formation of PHF-like phosphorylated tau within the olfactory bulb. We discuss a possible involvement of modulatory input provided by cholinergic neurons in the basal forebrain, which are affected by hibernation.
Highlights
The microtubule-associated protein tau promotes polymerization (Weingarten et al, 1975), stabilizes existing microtubules (Drechsel et al, 1992), organizes them into bundles (Elie et al, 2015) and mediates interaction of microtubules with filamentous actin (Biswas and Kalil, 2017; Cabrales Fontela et al, 2017)
The majority of antibodies showed a significant increase in phosphorylation at their respective epitopes during torpor, which was fully reversible after arousal (Figure 1E)
We combined behavioral, biochemical and morphological analyses to investigate whether hibernation induced phosphorylation of tau in the main olfactory bulb is associated with synaptic regression and a loss of long-term memory for discrimination of odors
Summary
The microtubule-associated protein tau promotes polymerization (Weingarten et al, 1975), stabilizes existing microtubules (Drechsel et al, 1992), organizes them into bundles (Elie et al, 2015) and mediates interaction of microtubules with filamentous actin (Biswas and Kalil, 2017; Cabrales Fontela et al, 2017). Long before the formation of PHFs and subsequent neuronal degeneration, the presence of hyperphosphorylated tau in the post-synaptic compartments leads to the deterioration of synaptic plasticity and cognitive decline (Yoshiyama et al, 2007; Hoover et al, 2010; Ittner et al, 2010; Morris et al, 2011). This is supported by the presence of tau aggregates in dendritic spines (Blazquez-Llorca et al, 2011) at very early stages of Alzheimer’s disease
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