A new model of cuprizone-mediated demyelination/remyelination.

In the central nervous system, demyelinating diseases, such as multiple sclerosis, result in devastating long-term neurologic damage, in part because of the lack of effective remyelination in the adult human brain. One model used to understand the mechanisms regulating remyelination is cuprizone-induced demyelination, which allows investigation of remyelination mechanisms in adult animals following toxin-induced demyelination. Unfortunately, the degree of demyelination in the cuprizone model can vary, which complicates understanding the process of remyelination.

Conditional ablation of raptor or rictor has differential impact on oligodendrocyte differentiation and CNS myelination.

During CNS development, oligodendrocytes, the myelinating glia of the CNS, progress through multiple transitory stages before terminating into fully mature cells. Oligodendrocyte differentiation and myelination is a tightly regulated process requiring extracellular signals to converge to elicit specific translational and transcriptional changes. Our lab has previously shown that the protein kinases, Akt and mammalian Target of Rapamycin (mTOR), are important regulators of CNS myelination in vivo.

The dependence on gp130 cytokines of axotomy induced neuropeptide expression in adult sympathetic neurons.

Adult peripheral neurons exhibit dramatic changes in gene expression after axonal injury, including changes in neuropeptide phenotype. For example, sympathetic neurons in the superior cervical ganglion (SCG) begin to express vasoactive intestinal peptide (VIP), galanin, pituitary adenylate cyclase activating polypeptide (PACAP), and cholecystokinin after axotomy. Before these changes, nonneuronal cells in the SCG begin to express leukemia inhibitory factor (LIF).

Galanin plays a role in the conditioning lesion effect in sensory neurons.

Sensory neurons show enhanced neurite outgrowth in vivo and in vitro following a conditioning lesion. Previous studies have shown that these effects are dependent on two members of the gp130 family of cytokines, leukemia inhibitory factor and interleukin-6. Here, we asked whether galanin, a neuropeptide induced by these cytokines, plays a role in the conditioning lesion response.

Novel changes in gene expression following axotomy of a sympathetic ganglion: a microarray analysis.

Neurons of the peripheral nervous system are capable of extensive regeneration following axonal injury. This regenerative response is accompanied by changes in gene expression in axotomized neurons and associated nonneuronal cells. In the sympathetic nervous system, a few of the genes affected by axonal injury have been identified; however, a broad sampling of genes that could reveal additional and unexpected changes in expression has been lacking.