Tau phosphorylation-associated spine regression does not impair hippocampal-dependent memory in hibernating golden hamsters.
The microtubule-associated protein tau, in its hyperphosphorylated form, is the major component of paired helical filaments and other aggregates in neurodegenerative disorders commonly referred to as "tauopathies". Recent evidence, however, indicates that mislocalization of hyperphosphorylated tau to subsynaptic sites leads to synaptic impairment and cognitive decline even long before formation of tau aggregates and neurodegeneration occur. A similar, but reversible hyperphosphorylation of tau occurs under physiologically controlled conditions during hibernation. Here, we study the hibernating Golden hamster (Syrian hamster, Mesocricetus auratus). A transient spine reduction was observed in the hippocampus, especially on apical dendrites of hippocampal CA3 pyramidal cells, but not on their basal dendrites. This distribution of structural synaptic regression was correlated to the distribution of phosphorylated tau, which was highly abundant in apical dendrites but hardly detectable in basal dendrites. Surprisingly, hippocampal memory assessed by a labyrinth maze was not affected by hibernation. The present study suggests a role for soluble hyperphosphorylated tau in the process of reversible synaptic regression, which does not lead to memory impairment during hibernation. We hypothesize that tau phosphorylation associated spine regression might mainly affect unstable/dynamic spines while sparing established/stable spines.
Department of Molecular and Cellular Mechanisms of Neurodegeneration, Paul Flechsig Institute of Brain Research, University of Leipzig, Leipzig, Germany.|Frey Initiative Research Unit, RIKEN Quantitative Biology Center, Japan.
Torsten
T
Bullmann
Department of Molecular and Cellular Mechanisms of Neurodegeneration, Paul Flechsig Institute of Brain Research, University of Leipzig, Leipzig, Germany.
Gudrun
G
Seeger
Department of Molecular and Cellular Mechanisms of Neurodegeneration, Paul Flechsig Institute of Brain Research, University of Leipzig, Leipzig, Germany.
Jens
J
Stieler
MTA-SE NAP B Research Group of Experimental Neuroanatomy and Developmental Biology, Hungarian Academy of Sciences, Budapest, Hungary.|Department of Anatomy, Semmelweis University, Budapest, Hungary.
János
J
Hanics
Department of Molecular and Cellular Mechanisms of Neurodegeneration, Paul Flechsig Institute of Brain Research, University of Leipzig, Leipzig, Germany.
Katja
K
Reimann
Department of Molecular and Cellular Mechanisms of Neurodegeneration, Paul Flechsig Institute of Brain Research, University of Leipzig, Leipzig, Germany.
Tanja Petra
TP
Kretzschmann
Department of Molecular and Cellular Mechanisms of Neurodegeneration, Paul Flechsig Institute of Brain Research, University of Leipzig, Leipzig, Germany.
Isabel
I
Hilbrich
Department of Molecular and Cellular Mechanisms of Neurodegeneration, Paul Flechsig Institute of Brain Research, University of Leipzig, Leipzig, Germany.
Max
M
Holzer
MTA-SE NAP B Research Group of Experimental Neuroanatomy and Developmental Biology, Hungarian Academy of Sciences, Budapest, Hungary.|Department of Anatomy, Semmelweis University, Budapest, Hungary.
Alán
A
Alpár
Department of Molecular and Cellular Mechanisms of Neurodegeneration, Paul Flechsig Institute of Brain Research, University of Leipzig, Leipzig, Germany.
Thomas
T
Arendt
D000818:Animals; D001143:Arousal / Q000502:physiology; D006224:Cricetinae; D049229:Dendritic Spines / Q000378:metabolism*; D000076122:Disks Large Homolog 4 Protein; D005260:Female; D006605:Hibernation / Q000502:physiology*; D006624:Hippocampus / Q000166:cytology* / Q000378:metabolism; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D008297:Male; D018782:Maze Learning; D008565:Membrane Proteins / Q000378:metabolism; D008568:Memory / Q000502:physiology*; D008647:Mesocricetus / Q000502:physiology; D009043:Motor Activity; D009474:Neurons / Q000648:ultrastructure*; D016415:Sequence Alignment; D013569:Synapses / Q000502:physiology; D013997:Time Factors; D064348:Torpor / Q000502:physiology; D016875:tau Proteins / Q000378:metabolism*
C501444:DLG4 protein, human; D000076122:Disks Large Homolog 4 Protein; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D016875:tau Proteins
Alzheimer's disease; hypometabolism; microtubule associated protein; protein phosphorylation; torpor