Eldon E. Geisert

Distribution and characteristics of a 90 kDa protein, KG-CAM, in the rat CNS

The distribution of a 90 kDa protein, termed KG-CAM, was examined in the developing and adult rat central nervous system (CNS) using the monoclonal antibody 11-59. The amino acid sequence of this protein revealed a sequence homology with a group of chick cell adhesion molecules from the immunoglobulin superfamily: DM-GRASP; SC1; and BEN. Immunolabeling of cells cultured from the embryonic and neonatal rat brain demonstrates that the protein recognized by 11-59 is on the external surface of a subpopulation of neurons and a limited population of glial cells. When the 11-59 antibody was used to stain sections of the adult brain and spinal cord, a number of different structures were labeled. The most intense immunoreactivity was found in the somatosensory system, the basal ganglia, the cortex, the olfactory system, and the circumventricular organs. One of the more interesting aspects of KG-CAM is the spatially and temporally regulated patterns of expression observed during the development of the CNS. For example, the dendrites of layer II pyramidal cells in the granular retrosplenial cortex are immunopositive for 11-59 while the dendrites are in the process of bundling in layer I, but not before bundling begins or after the process is completed. These findings reveal the varied roles of this adhesion molecule in the developing brain and spinal cord, as well as its potential role in the maintenance of the structural integrity of the adult CNS.

α2-Adrenergic receptor-mediated modulation of calcium current in neocortical pyramidal neurons

Noradrenergic projections to the cortex modulate a variety of cortical activities and calcium channels are one likely target for such modulation. We used the whole-cell patch-clamp technique to study noradrenergic modulation of barium currents in acutely dissociated pyramidal neurons from rat sensorimotor cortex. Extracellular application of specific agonists and antagonists revealed that norepinephrine (NE) reduced Ca2+ current. A major component of this modulation was due to activation of alpha2 receptors. Activation of alpha2-adrenergic receptors resulted in a fast, voltage-dependent pathway involving Gi/Go G-proteins. This pathway targeted N- and P-type calcium channels The alpha2 modulation was partially reversed by repeated action potential waveforms (APWs). N- and P-type channels have been implicated in synaptic transmission and activation of afterhyperpolarizations in these cells. Our findings suggest that NE can regulate these cellular processes by mechanisms sensitive to spike activity.

N-cadherin at the glial scar in the rat

Following injury to the central nervous system (CNS), astrocytes become reactive and in many cases form a glial scar. Very little is known about the adhesive interactions between astrocytes at the glial scar, even though reactive gliosis and scar formation are a central issue in CNS wound healing. In the present study, we examine the role of cadherin in the process of scar formation using immunohistochemistry and immunoblot methods. When a stab wound was made in the cerebral cortex of the rat, cadherins were consistently upregulated by the reactive astrocytes at the glial scar. Our immunoblot analysis demonstrates that the increase in cadherin immunoreactivity was due to a threefold upregulation of a single protein with a molecular weight of 135 kDa. The size (135 kDa) and location of the immunoreactive protein at regions of cell-cell contact in cultured astrocytes indicates that the immunoreactive protein is N-cadherin. These data are the first to demonstrate that N-cadherin plays a prominent role in the response of astrocytes to injury, including the formation and maintenance of the glial scar.

Special Issue in Honor of Dr. Dianna Johnson

It is a privilege to be the guest editor of the special issue honoring Dr. Dianna (Redburn) Johnson. Dr. Johnson has a long and exemplary career, serving as a role model for many young scientists. Dianna’s entre to neuroscience began in 1967 with a chance interview with Dr. Fred Samson, Chair of the Department of Physiology and Cell Biology at the University of Kansas, who had just returned the previous month from a sabbatical at UCLA to learn more about the emerging discipline of neurochemistry. Caught up in his fresh enthusiasm and a new appreciation of the complexities of the chemistry of the brain, Dianna signed up as his graduate student to study microtubules, Dr. Dianna Johnson