Mechanisms which regulate the cholinergic phenotype in sympathetic, central cholinergic and spinal motoneurons

ABSTRACTS

490

Mechanisms which regulate the cholinergic phenotype in sympathetic, central cholinergic and spinal motoneurons M. Sendtner

Besides their function in supporting neuronal survival, neurotrophic factors influence various functional properties of responsive neurons. In cell culture, neurotrophic factors of the CNTF/LIF family can switch the transmitter phenotype of sympathetic neurons from adrenergic to cholinergic (Schotringer and Landis, 1990; Saadat et al., 1989; Ernsberger et al., 1997), and choline acetyl transferase expression both in central cholinergic neurons as well as in spinal motoneurons is influenced by neurotrophic factors (Gnahn et al., 1983: Magal et al., 1991; Williams et al., 1996; Wang et al., 1993; Alderson et al., 1996;). Although these mechanisms have been studied in detail in cell culture, it is not clear whether the same factors also regulate cholinergic transmitter production of these neurons in viva. Ciliary neurotrophic factor and leukemia-inhibitory factor are not expressed within the innervated target region of cholinergic neurons such as sweat gland and skeletal muscle (StGckli et al.. 1991; Banner and Patterson. 1993). Instead. they are found in Schwann cells within the peripheral nerve and astrocytes within the central nervous system. In particular ;after peripheral nerve or mechanical brain lesion, the production of LIF is increased, and CNTF can be released in order IO act on lesioned cholinergic neurons (Sendtner et al.. 1997). Currently. mouse mutants lacking the genes for neurotrophic factors (DeChiara et al., 1995; Li et al., 1995; Sendtner et al., 1996; Francis et al., 1997) are analyzed to define the physiological endogenous role of these factors in regulating the cholinergic phenotype of these neurons.

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residues and 5 disulfide bonds) (Endo and Tamiya, 1991). On the basis of electrophysiological and binding experiments, we rccently demonstrated that only long-chain toxins possessing 5 disulfide bonds are capable of blocking the ~r7 neuronal acetylcholine re-