Dataset Information

Hibernation Impairs Odor Discrimination - Implications for Alzheimer's Disease.

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.

SUBMITTER: Bullmann T

PROVIDER: S-EPMC6646461 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Hibernation Impairs Odor Discrimination - Implications for Alzheimer's Disease.

Bullmann Torsten T Feneberg Emily E Kretzschmann Tanja Petra TP Ogunlade Vera V Holzer Max M Arendt Thomas T

Frontiers in neuroanatomy 20190716

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, <i>Mesocricetus auratus</i>). 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 plasticit ...[more]

PMID: 31379517

Similar Datasets

Project description:Introduction: Cholinergic Receptor Muscarinic 1 (CHRM1) is a G protein-coupled acetylcholine (ACh) receptor predominantly expressed in the cerebral cortex. In a retrospective postmortem brain tissues-based study, we demonstrated that severely (≥50% decrease) reduced CHRM1 proteins in the temporal cortex of Alzheimer's patients significantly correlated with poor patient outcomes. The G protein-mediated CHRM1 signal transduction cannot sufficiently explain the mechanistic link between cortical CHRM1 loss and the appearance of hallmark Alzheimer's pathophysiologies, particularly mitochondrial structural and functional abnormalities. Therefore, the objective of this study was to analyze the molecular, ultrastructural, and functional properties of cortical mitochondria using CHRM1 knockout (Chrm1-/-) and wild-type mice to identify mitochondrial abnormalities. Methods: Isolated and enriched cortical mitochondrial fractions derived from wild-type and Chrm1-/- mice were assessed for respiratory deficits (oxygen consumption) following the addition of different substrates. The supramolecular assembly of mitochondrial oxidative phosphorylation (OXPHOS)-associated protein complexes (complex I-V) and cortical mitochondrial ultrastructure were investigated by blue native polyacrylamide gel electrophoresis and transmission electron microscopy (TEM), respectively. A cocktail of antibodies, specific to Ndufb8, Sdhb, Uqcrc2, Mtco1, and Atp5a proteins representing different subunits of complexes I-V, respectively was used to characterize different OXPHOS-associated protein complexes. Results: Loss of Chrm1 led to a significant reduction in cortical mitochondrial respiration (oxygen consumption) concomitantly associated with reduced oligomerization of ATP synthase (complex V) and supramolecular assembly of complexes I-IV (Respirasome). Overexpression of Chrm1 in transformed cells (lacking native Chrm1) significantly increased complex V oligomerization and respirasome assembly leading to enhanced respiration. TEM analysis revealed that Chrm1 loss led to mitochondrial ultrastructural defects and alteration in the tinctorial properties of cortical neurons causing a significant increase in the abundance of dark cortical neurons (Chrm1-/- 85% versus wild-type 2%). Discussion: Our findings indicate a hitherto unknown effect of Chrm1 deletion in cortical neurons affecting mitochondrial function by altering multiple interdependent factors including ATP synthase oligomerization, respirasome assembly, and mitochondrial ultrastructure. The appearance of dark neurons in Chrm1-/- cortices implies potentially enhanced glutamatergic signaling in pyramidal neurons under Chrm1 loss condition. The findings provide novel mechanistic insights into Chrm1 loss with the appearance of mitochondrial pathophysiological deficits in Alzheimer's disease.

Dataset Information

Hibernation Impairs Odor Discrimination - Implications for Alzheimer's Disease.

Publications

Hibernation Impairs Odor Discrimination - Implications for Alzheimer's Disease.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets