Lesion-induced axonal sprouting in the central nervous system.
Injury or neuronal death often come about as a result of brain disorders. Inasmuch as the damaged nerve cells are interconnected via projections to other regions of the brain, such lesions lead to axonal loss in distal target areas. The central nervous system responds to deafferentation by means of plastic remodeling processes, in particular by inducing outgrowth of new axon collaterals from surviving neurons (collateral sprouting). These sprouting processes result in a partial reinnervation, new circuitry, and functional changes within the deafferented brain regions. Lesioning of the entorhinal cortex is an established model system for studying the phenomenon of axonal sprouting. Using this model system, it could be shown that the sprouting process respects the pre-existing lamination pattern of the deafferented fascia dentata, i. e., it is layer-specific. A variety of different molecules are involved in regulating this reorganization process (extracellular matrix molecules, cell adhesion molecules, transcription factors, neurotrophic factors, growth-associated proteins). It is proposed here that molecules of the extracellular matrix define the boundaries of the laminae following entorhinal lesioning and in so doing limit the sprouting process to the deafferented zone. To illustrate the role of axonal sprouting in disease processes, special attention is given to its significance for neurodegenerative disorders, particularly Alzheimer's disease (AD), and temporal lobe epilepsy. Finally, we discuss both the beneficial as well as disadvantageous functional implications of axonal sprouting for the injured organism in question.
Deller
Thomas
T
Institute of Clinical Neuroanatomy, Johann Wolfgang Goether-University, Frankfurt am Main, Germany.
Haas
Carola A
CA
Freiman
Thomas M
TM
Phinney
Amie
A
Jucker
Mathias
M
Frotscher
Michael
M
D000544:Alzheimer Disease / Q000473:pathology / Q000503:physiopathology; D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000378:metabolism; D001369:Axons / Q000502:physiology* / Q000648:ultrastructure; D002490:Central Nervous System / Q000166:cytology / Q000473:pathology / Q000502:physiology*; D002493:Central Nervous System Diseases / Q000473:pathology / Q000503:physiopathology; D018728:Entorhinal Cortex / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D004833:Epilepsy, Temporal Lobe / Q000473:pathology / Q000503:physiopathology; D005109:Extracellular Matrix / Q000737:chemistry / Q000378:metabolism; D006801:Humans