No abstract

The subpopulation of dorsal root ganglion (DRG) neurons recognized by Griffonia simplicifolia isolectin B4 (IB4) differ from other neurons by expressing receptors for glial cell line-derived neurotrophic factor (GDNF) rather than neurotrophins. Additionally, IB4-labeled neurons do not express the laminin receptor, ␣7-integrin (Gardiner et al., 2005), necessary for optimal axonal regeneration in the peripheral nervous system. In cultures of dissociated DRG neurons of adult mice on laminin, robust spontaneous neurite outgrowth from IB4-negative neurons occurs and is strongly enhanced by previous axotomy. In contrast, IB4-labeled neurons show little neurite outgrowth and do not express GAP 43, even after axotomy or culture with GDNF. Moreover, growth of their axons through collagen gels is impaired compared with other DRG neurons. To determine whether the sparse neurite outgrowth of IB4-labeled neurons is attributable to lack of integrin expression, DRG cultures were infected with a herpes simplex 1 vector encoding ␣7-integrin, but its forced expression failed to promote neurite outgrowth in either IB4-labeled or other DRG neurons or in cultured adult retinal ganglion cells. Forced coexpression of both ␣7-integrin and GAP 43 also failed to promote neurite outgrowth in IB4-labeled neurons. In addition, cultured sciatic nerve segments were found to release much lower levels of GDNF, demonstrated by ELISA, than nerve growth factor. These findings together with their impaired intrinsic axonal regeneration capacity may contribute to the known vulnerability of the IB4-labeled population of DRG neurons to peripheral nerve injury.

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1. A sublethal dose of botulinum toxin (type A) was injected into the muscles of one hind limb of the mouse causing local paralysis. 2. Neuromuscular transmission and muscle sensitivity to acetylcholine (ACh) were studied in vitro in soleus and extensor digitorium longus (EDL) from 6 hr to 4 months after the injection of toxin. 3. Both soleus and EDL failed to respond to nerve stimulation within 6 hr of the injection of toxin. 4. In muscle fibres in which neuromuscular transmission was blocked, subthreshold end‐plate potentials (e.p.p.s) were recorded. The amplitude of the e.p.p.s increased during recovery from the effects of the toxin and both muscles contracted in response to nerve stimulation after 2‐3 weeks. 5. For about 2 months muscles fatigued more rapidly than normal during repetitive nerve stimulation because of the low quantal content of e.p.p.s. 6. Supersensitivity to ACh developed in 3‐5 days and persisted after the return of neuromuscular transmission. Muscle sensitivity to ACh became normal when the rate of fatigue during nerve stimulation was normal.