Abstract
There are many microtubules in axons and dendritic shafts, but it has been thought that there were fewer microtubules in spines. Recently, there have been four reports that observed the intraspinal microtubules. Because microtubules originate from the centrosome, these four reports strongly suggest a stimulation-dependent connection between the nucleus and the stimulated postsynaptic membrane by microtubules. In contrast, several pieces of evidence suggest that spine elongation may be caused by the polymerization of intraspinal microtubules. This structural mechanism for spine elongation suggests, conversely, that the synapse loss or spine loss observed in Alzheimer's disease may be caused by the depolymerization of intraspinal microtubules. Based on this evidence, it is suggested that the impairment of intraspinal microtubules may cause spinal structural change and block the translocation of plasticity-related molecules between the stimulated postsynaptic membranes and the nucleus, resulting in the cognitive deficits of Alzheimer's disease.
Highlights
What is the precise mechanism of memory disturbance in patients with Alzheimer’s disease (AD)? For the mechanism of memory storage in the normal brain, it is commonly believed that a long-lasting change in synaptic function is the cellular basis of learning and memory [1,2,3], especially at the hippocampal Schaffer collateral synapses on CA1 pyramidal cells
Normal tau is primarily present in the axon, but hyperphosphorylated tau newly distributes to dendrites and sequesters microtubule-associated proteins (MAPs) such as normal tau, MAP1A/MAP1B, and MAP2 [38] and may cause the inhibition and disruption of intraspinal microtubules by losing the microtubule-preserving effect of MAPs
In our report, based on acute hippocampal slices that were fixed by a microtubule conserving process after long-term potentiation (LTP)-inducing stimulation, we showed that microtubules of the dendritic shaft ramified into spines (Figure 1) into the stimulated postsynaptic membranes (Figure 2)
Summary
What is the precise mechanism of memory disturbance in patients with Alzheimer’s disease (AD)? For the mechanism of memory storage in the normal brain, it is commonly believed that a long-lasting change in synaptic function is the cellular basis of learning and memory [1,2,3], especially at the hippocampal Schaffer collateral synapses on CA1 pyramidal cells. The second discovery described above was an important step toward understanding the mechanisms of memory storage, but the specificity of plasticity at stimulated synapses, International Journal of Alzheimer’s Disease as occurs in CA1 neurons, may require other mechanisms in addition to an increase in the transcription level To explain this synaptic specificity, the synaptic tagging theory proposes that a tag is activated in activated synapses, and this localizes the effects of plasticity-promoting molecules that otherwise travel nonspecifically in the neuron [17,18,19,20]. Normal tau is primarily present in the axon, but hyperphosphorylated tau newly distributes to dendrites and sequesters microtubule-associated proteins (MAPs) such as normal tau, MAP1A/MAP1B, and MAP2 [38] and may cause the inhibition and disruption of intraspinal microtubules by losing the microtubule-preserving effect of MAPs. it may be strongly suggested that amyloid beta may be a putative intraspinal microtubule-depolymerizer to induce spine loss and synaptic loss, resulting in the impairment of the bidirectional dendritic transports and the memory disturbance in AD
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