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Marian Kies Memorial Award for 1997
Dr. Karen Chandross

Dr. Karen Chandross

The focus of my thesis research was to better understand mechanisms underlying the synchronous responses of Schwann cells after peripheral nerve injury. These responses, which include cellular dedifferentiation, proliferation, and the eventual remyelination of axons, are critical for successful nerve regeneration and repair. The basic hypothesis was that cytokines released after nerve injury contribute towards the initiation and ultimately the termination of Schwann cell responses in the affected region. A specific hypothesis that emerged is that the cytokine-induced regulation of gap junctional communication among Schwann cells may help to coordinate responses to nerve injury. Gap junctions are specialized channels that form between cells and allow the direct cell-to-cell diffusion of ions, amino acids, and second messenger molecules. Myelinating Schwann cells, which are mitotically quiescent, express the gap junction protein connexin32 (Cx32), however, in my studies, they do not appear to be coupled to one another. Instead, Cx32 is believed to form reflexive contacts within individual myelinating glial cells and provide direct pathways for intracellular ionic and metabolic exchange from the cell body to the innermost periaxonal cytoplasmic regions. After nerve injury, I observed that proliferating (dedifferentiated) Schwann cells in the degenerating region down-regulate expression of Cx32 and increase expression of Cx46, a gap junction protein previously identified only in lens. After re-contact with regenerating axons Schwann cells again become uncoupled, suggesting a function for gap junction channels between cells after nerve injury. Moreover, the strength of junctional coupling among cultured Schwann cells is modulated by a number of cytokines to which Schwann cells are exposed to after nerve injury, and Cx46 levels correlate with the degree of coupling. The cascade of Schwann cell responses seen after the injury-induced decreases in Cx32, and the observation that reactive Schwann cells express Cx46, and possibly other connexins, and are strongly coupled through gap junction channels, raise the intriguing possibility that these specialized channels, under the control of local cues (i.e., inflammatory cytokines), play an instrumental role in coordinating the synchronous responses observed n these cells during injury responses.