Spiegel I, Peles E.
A new player in CNS myelination.
Neuron. 2006 Mar 16;49(6):777-8.
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This paper has significant potential implications for multiple sclerosis, and one can reasonably speculate about potential relevance to Alzheimer disease, as well. The general principle the authors are describing, that is, that electrical activity in neurons releases a signal—in this case ATP—that tells the astrocytes to release other signals that then feed back on neighboring cells such as oligodendrocytes is quite interesting.
One possible connection to neurodegenerative disease is that there is much evidence that astrocytes are releasing signals that are crucial for the promotion of CNS neuron survival, though no one yet knows what these astrocyte-derived trophic signals are. Could electrical activity in neurons induce astrocytes to release more of these neurotrophic signals? If so, decreased activity with aging or in neurodegenerative disease certainly might lead to less release of trophic signals (which in turn could lead to failure of myelin maintenance).
In fact, I showed previously that LIF and CNTF are co-mitogens for oligodendrocyte precursor cells (Barres et al., 1993). If activity is inducing astrocytes to release LIF, this could mean that when activity is blocked, there is also less proliferation of oligodendrocyte precursor cells and therefore less new oligodendrocyte generation. Over time, this might lead to loss of myelin in humans. Such a loss of myelin has recently been found in the temporal lobes of patients with major depressive disorder (Aston et al., 2005). I wonder if decreased activity in a temporal lobe pathway, perhaps because of stress, might eventually lead to depression by causing myelin loss. If so, then it’s fair to speculate that major depressive disorder could be a type of neurodegenerative disease.
Barres BA, Schmid R, Sendnter M, Raff MC.
Multiple extracellular signals are required for long-term oligodendrocyte survival.
Development. 1993 May;118(1):283-95.
Kulartz M, Hiller E, Kappes F, Pinna LA, Knippers R.
Protein kinase CK2 phosphorylates the cell cycle regulatory protein Geminin.
Biochem Biophys Res Commun. 2004 Mar 19;315(4):1011-7.
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