title: Synaptic plasticity and cell cycle activation in neurons are alternative effector pathways: the 'Dr. Jekyll and Mr. Hyde concept' of Alzheimer's disease or the yin and yang of neuroplasticity.
abstract: Mental actions are based on the dynamic organization of neuronal networks. In particular, phylogenetically young brain areas (e.g., cortical associative circuits) involved in the realization of higher brain functions are continuously re-adjusted to meet environmental demands. The mechanisms of synaptic plasticity, i.e., of structural stabilization and labilization underlying a life-long synaptic remodelling, are largely based on external morphoregulatory cues and internal signalling pathways that non-neuronal cells have phylogenetically acquired to sense their relationship to the local neighbourhood and to control after development is completed proliferation and differentiation in the process of tissue repair and regeneration. After having withdrawn from the cell cycle, differentiated neurons are, thus, able to use molecular mechanisms primarily developed to control proliferation alternatively to control synaptic plasticity. The existence of these alternative effector pathways within a neuron puts it at risk to erroneously convert signals derived from plastic synaptic changes into positional cues that will activate the cell cycle. This cell cycle activation potentially links synaptic plasticity to cell death. Preventing cell cycle activation by locking neurons in a differentiated but still highly plastic phenotype will, thus, be crucial to prevent neurodegeneration.
authors.affiliation: Paul Flechsig Institute of Brain Research, Department of Neuroanatomy, University of Leipzig, Jahnallee 59, D-04109, Leipzig, Germany. aret@medizin.uni-leipzig.de
authors.forename: Thomas
authors.initials: T
authors.lastname: Arendt
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology* / Q000503:physiopathology; D000818:Animals; D002453:Cell Cycle / Q000502:physiology*; D006801:Humans; D009434:Neural Pathways / Q000502:physiology; D009473:Neuronal Plasticity / Q000502:physiology*; D009474:Neurons / Q000378:metabolism*; D013569:Synapses / Q000502:physiology*