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We have used antibodies to identify Schwann cells and oligodendrocytes and to study the expression of myelin-specific glycolipids and proteins in these cells isolated from perinatal rats. Our findings suggest that only Schwann cells which have been induced to myelinate make detectable amounts of galactocerebroside (GC), sulfatide, myelin basic protein (BP), or the major peripheral myelin glycoprotein (Po) . When rat Schwann cells were cultured, they stopped making detectable amounts of these myelin molecules, even when the cells were associated with neurites in short-term explant cultures of dorsal root ganglion . In contrast, oligodendrocytes in dissociated cell cultures of neonatal optic nerve, corpus callosum, or cerebellum continued to make GC, sulfatide and BP for many weeks, even in the absence of neurons. These findings suggest that while rat Schwann cells require a continuing signal from appropriate axons to make detectable amounts of myelin-specific glycolipids and proteins, oligodendrocytes do not .Schwann cells and oligodendrocytes also displayed very different morphologies in vitro which appeared to reflect their known differences in myelinating properties in vivo . Since these characteristic morphologies were maintained when Schwann cells and oligodendrocytes were grown together in mixed cultures and in the absence of neurons, we concluded that they are intrinsic properties of these two different myelin-forming cells .KEY WORDS Schwann cells oligodendrocytes " myelin " basic protein galactocerebroside dissociated cell culturesOne of the most remarkable examples of cell-cell interaction in the nervous system is the formation of myelin around neuronal axons by myelin-forming glial cells . Schwann cells in the peripheral nervous system (9) and oligodendrocytes in the central nervous system (16, 21) wrap their plasma membranes concentrically around axons to form multilayered myelin sheaths . Although myelin has been the subject of intensive biophysical and biochemical study, remarkably little is known about the molecular events involved in myelination . It seems likely that a detailed understanding of these events will require studying the process in vitro, preferably in dissociated cultures of purified myelin-forming cells mixed with purified neurons. Recently, we have defined surface antigenic markers which allow Schwann cells and oligodendrocytes to be unambiguously identified in dissociated cell cultures of peripheral and central nervous tissues, respectively . Rat neural antigen-1 J. CELL BIOLOGY

Objective Acute pancreatitis is caused by toxins that induce acinar cell calcium overload, zymogen activation, cytokine release and cell death, yet is without specific drug therapy. Mitochondrial dysfunction has been implicated but the mechanism not established. Design We investigated the mechanism of induction and consequences of the mitochondrial permeability transition pore (MPTP) in the pancreas using cell biological methods including confocal microscopy, patch clamp technology and multiple clinically representative disease models. Effects of genetic and pharmacological inhibition of the MPTP were examined in isolated murine and human pancreatic acinar cells, and in hyperstimulation, bile acid, alcoholic and choline-deficient, ethionine-supplemented acute pancreatitis. Results MPTP opening was mediated by toxin-induced inositol trisphosphate and ryanodine receptor calcium channel release, and resulted in diminished ATP production, leading to impaired calcium clearance, defective autophagy, zymogen activation, cytokine production, phosphoglycerate mutase 5 activation and necrosis, which was prevented by intracellular ATP supplementation. When MPTP opening was inhibited genetically or pharmacologically, all biochemical, immunological and histopathological responses of acute pancreatitis in all four models were reduced or abolished. Conclusions This work demonstrates the mechanism and consequences of MPTP opening to be fundamental to multiple forms of acute pancreatitis and validates the MPTP as a drug target for this disease.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by progressive death of cortical and spinal motor neurons, for which there is no effective treatment. Using a cell-based assay for compounds capable of preventing motor neuron cell death in vitro, a collection of approximately 40,000 low-molecular-weight compounds was screened to identify potential small-molecule therapeutics. We report the identification of cholest-4-en-3-one, oxime (TRO19622) as a potential drug candidate for the treatment of ALS. In vitro, TRO19622 promoted motor neuron survival in the absence of trophic support in a dose-dependent manner. In vivo, TRO19622 rescued motor neurons from axotomy-induced cell death in neonatal rats and promoted nerve regeneration following sciatic nerve crush in mice. In SOD1G93A transgenic mice, a model of familial ALS, TRO19622 treatment improved motor performance, delayed the onset of the clinical disease, and extended survival. TRO19622 bound directly to two components of the mitochondrial permeability transition pore: the voltage-dependent anion channel and the translocator protein 18 kDa (or peripheral benzodiazepine receptor), suggesting a potential mechanism for its neuroprotective activity. TRO19622 may have therapeutic potential for ALS and other motor neuron and neurodegenerative diseases.Amyotrophic lateral sclerosis (ALS) is a rapidly progressive neurodegenerative disorder that selectively affects motor neurons in the spinal cord, brainstem, and cortex. ALS affects people of all races and ethnic backgrounds with an incidence approximately 2 per 100,000 individuals (McGuire and Nelson, 2006). The onset of ALS is most common in the 55 to 75 year age range, and incidence rises with advancing age; men have a higher risk of developing the disease than women (Nelson, 1995). Common clinical features of ALS include muscle weakness and fasciculations. These occur predominantly in limbs, although bulbar onset pathology can also lead to tongue atrophy and dysphagia. Failure of the respiratory muscles and cardiac complications are generally the fatal event, occurring within an average of 3 years of disease onset, with only a 5% chance of survival 5 years after diagnosis (del Aguila et al., 2003). Although 5 to 10% of ALS This work was supported by the Association Française contre les Myopathies.1 Current affiliation: Center for Motor Neuron Biology and Disease, Columbia University, New York.Article, publication date, and citation information can be found at