The potent melanocortin receptor agonist melanotan-II promotes peripheral nerve regeneration and has neurroprotective properties in rat

The neurotrophic and neuroprotective potential of the -melanocyte-stimulating hormone (-MSH) analog cyclo-[Ac-Nle4,Asp5,-Phe7,Lys10]-MSH-(410) amide (melanotan-II), a potent melanocortin receptor agonist, was investigated. The sciatic nerve crush model was used as a paradigm to investigate the neurotrophic properties of melanotan-II. Melanotan-II significantly enhanced the recovery of sensory function following a crush lesion of the sciatic nerve in the rat at a dose of 20 g kg−1 per 48 h, s.c., but not at a dose of 2 or 50 g kg−1. In addition, we observed that melanotan-II also possesses neuroprotective properties, as it partially protected the nerve from a toxic neuropathy induced by cisplatin. Thus, the present data for the first time demonstrate the effectiveness of the potent -MSH analog melanotan-II in nerve regeneration and neuroprotection

Locomotor recovery after spinal cord contusion injury in rats is improved by spontaneous exercise

We have recently shown that enriched environment (EE) housing significantly enhances locomotor recovery following spinal cord contusion injury (SCI) in rats. As the type and intensity of locomotor training with EE housing are rather poorly characterized, we decided to compare the effectiveness of EE housing with that of voluntary wheel running, the latter of which is both well characterized and easily quantified. Female Wistar rats were made familiar with three types of housing conditions, social housing (nine together) in an EE (EHC), individual housing in a running wheel cage (RUN, n = 8), and standard housing two together (CON, n = 10). Subsequently, a 12.5 gcm SCI at Th8 was produced and animals were randomly divided over the three housing conditions. Locomotor function was measured regularly, once a week by means of the BBB score, BBB sub score, TLH test, Gridwalk test, and CatWalk test. In the RUN group, daily distance covered was also measured. Locomotor recovery in the EHC and the RUN groups was equal and significantly better than in the CON group. The extent of recovery at 8 weeks post injury in the RUN group did not correlate with distance covered. We conclude that locomotor training needs to exceed a given threshold in order to be effective in enhancing locomotor recovery in this experimental model, but that once this threshold is exceeded no further improvement occurs, and that the specificity of locomotor training plays little role

Neurophysiological changes in the central and peripheral nervous system of streptozotocin-diabetic rats. Course of development and effects of insulin treatment

Diabetes mellitus can affect both the peripheral and the central nervous system. However, central deficits are documented less well than peripheral deficits. We therefore compared the course of development of neurophysiological changes in the central and peripheral nervous systems in streptozotocin-diabetic rats. Sciatic nerve conduction velocities and auditory and visual evoked potentials were measured prior to diabetes induction, and then monthly after diabetes induction for 6 months. In addition, the effect of insulin treatment was examined. Treatment was initiated after a diabetes duration of 6 months and was continued for 3 months. During treatment, evoked potentials and nerve conduction were measured monthly. In a third experiment, conduction velocities in ascending and descending pathways of the spinal cord were examined after 3 and 6 months of diabetes. Impairments of sciatic nerve conduction velocities developed fully during the first 2-3 months of diabetes. In contrast, increased latencies of auditory and visual evoked potentials developed only after 3-4 months of diabetes, and progressed gradually thereafter. Insulin treatment, initiated 6 months after induction of diabetes, improved both nerve conduction velocities and evoked potential latencies. Conduction velocities in the spinal cord tended to be reduced after 3 months of diabetes and were significantly reduced after 6 months of diabetes. The present study demonstrates that in streptozotocin-diabetic rats the course of development of peripheral and central neurophysiological changes differs. Peripheral impairments develop within weeks after diabetes induction, whereas central impairments take months to develop. Insulin can reverse both peripheral and central neurophysiological alterations

Pre- and postsynaptic localization of RC3/neurogranin in the adult rat spinal cord: an immunohistochemical study

RC3 (neurogranin; BICKS) is a neuron-specific calmodulin-binding protein kinase C substrate. Thus far, immunohistochemical studies on the localization of RC3 revealed its presence in all neuronal phenotypes, which were restricted to specific areas in the neostriatum, the neocortex, and the hippocampus. RC3 was mostly found in cell bodies and dendrites, with some infrequent presence in axonal profiles, i.e. in the internal capsule. Until now, RC3 expression was reported to be absent in the adult rat spinal cord. RC3 might, however, act as an intermediate of protein kinase C-mediated signaling pathways during synaptic development and plasticity. We hypothesized a role for this 78-amino-acid protein in dendritic plasticity occurring after spinal cord injury. To our surprise, an immunohistological analysis of the uninjured adult rat spinal cord revealed the presence of RC3-positive cell bodies and dendrites in specific regions in the gray matter. Interestingly, axon-containing structures, such as the dorsal and ventral corticospinal tract, were also found to be RC3-positive. This axonal labeling was confirmed by preembedding electron microscopy. In conclusion, we demonstrate here that RC3 is present in the adult rat spinal cord in pre- and postsynaptic structures