Experimental neurology
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Experimental neurology · Dec 1997
Truncated trkB receptors on nonneuronal cells inhibit BDNF-induced neurite outgrowth in vitro.
The function of truncated trkB receptors during nervous system plasticity and regeneration is currently unknown. The extensive nonneuronal localization of truncated trkB-T1 receptors, coupled with their up-regulation by CNS glial cells in response to injury, has led to the speculation that these receptors may sequester BDNF and NT-4/5 to reduce their local availability and, thus, limit axonal sprouting. Conversely, trkB-T1 receptors could bind and present neurotrophins to injured axons and facilitate their regeneration in a manor analogous to that proposed for p75(NTR) receptors on Schwann cells. ⋯ This ability of trkB-T1 receptors on the nonneuronal substratum to inhibit BDNF-induced neurite outgrowth can be overcome by the addition of high concentrations of BDNF (1 microg/ml). Binding assays using 125I-BDNF suggest that this inhibitory effect could be mediated via binding and internalization of BDNF by the trkB-T1 receptors on the 3T3 cells. These results provide strong support for the hypothesis that the up-regulation of trkB-T1 receptors on astrocytes following CNS lesions enhances the sequestration of the trkB ligands, BDNF and NT- 4/5, at the site of reactive gliosis and, thus, contributes to the inhibition of CNS axonal regeneration from neurons expressing trkB-kinase receptors by removing their ligands from the extracellular environment.
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Experimental neurology · Dec 1997
Endogenous repair after spinal cord contusion injuries in the rat.
Contusion injuries of the rat thoracic spinal cord were made using a standardized device developed for the Multicenter Animal Spinal Cord Injury Study (MASCIS). Lesions of different severity were studied for signs of endogenous repair at times up to 6 weeks following injury. Contusion injuries produced a typical picture of secondary damage resulting in the destruction of the cord center and the chronic sparing of a peripheral rim of fibers which varied in amount depending upon the injury magnitude. ⋯ These cells may contribute to the development of cellular trabeculae that provide a scaffolding within the lesion cavity that provides the substrates for cellular infiltration and regeneration of axons. Together, these observations suggest that the endogenous reparative response to spinal contusion injury is substantial. Understanding the regulation and restrictions on the repair processes might lead to better ways in which to encourage spontaneous recovery after CNS injury.
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Experimental neurology · Nov 1997
Comparative StudyRegulation of D-aspartate release and uptake in adult brain stem auditory nuclei after unilateral middle ear ossicle removal and cochlear ablation.
In young adult guinea pigs, the effects of unilateral ossicle removal and cochlear ablation were determined on transmitter release from glutamatergic presynaptic endings and glutamate inactivation via uptake. (i) D-[3H]Aspartate release and uptake were measured in subdivisions of the cochlear nucleus (CN) and in nuclei of the superior olive (SOC) and auditory midbrain (MB) up to 145 days after placing the lesions. Activities were compared to those from age-matched unlesioned controls. Fiber degeneration was visualized histologically. (ii) In the ipsilateral CN, changes in release and uptake were governed by the type of lesion. ⋯ Subsequently, the residual release and uptake increased in magnitude, consistent with strengthening of excitatory glutamatergic transmission. (iii) In the contralateral CN, after either lesion, changes in release and uptake usually matched those in the ipsilateral CN. Thus, the auditory pathway associated with the lesioned ear probably provided cues for the regulation of synaptic strength in the contralateral CN. (iv) Both lesions increased release in the SOC and MB, and uptake in the SOC, consistent with strengthening of excitatory glutamatergic transmission. Sparse fiber degeneration, suggesting axonal pruning, appeared in the SOC and MB after cochlear ablation. (v) The strengthening of excitatory glutamatergic transmission may facilitate and maintain symptoms such as loudness recruitment and tinnitus which often accompany hearing loss.
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Experimental neurology · Nov 1997
c-Jun expression in adult rat dorsal root ganglion neurons: differential response after central or peripheral axotomy.
The response of the mature central nervous system (CNS) to injury differs significantly from the response of the peripheral nervous system (PNS). Axotomized PNS neurons generally regenerate following injury, while CNS neurons do not. The mechanisms that are responsible for these differences are not completely known, but both intrinsic neuronal and extrinsic environmental influences are likely to contribute to regenerative success or failure. ⋯ Our results indicated that c-Jun was upregulated substantially in DRG neurons following a peripheral axotomy, but following a central axotomy, only 18% of the neurons expressed c-Jun. Following dorsal rhizotomy and transplantation, however, c-Jun expression was upregulated dramatically; under those experimental conditions, 63% of the DRG neurons were c-Jun-positive. These data indicate that c-Jun expression may be related to successful regenerative growth following both PNS and CNS lesions.
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Experimental neurology · Nov 1997
The cannabinoid receptor agonist WIN 55,212-2 reduces D2, but not D1, dopamine receptor-mediated alleviation of akinesia in the reserpine-treated rat model of Parkinson's disease.
The effects of the synthetic cannabinoid receptor agonist WIN 55,212-2 on dopamine receptor-mediated alleviation of akinesia were evaluated in the reserpine-treated rat model of parkinsonism. The dopamine D2 receptor agonist quinpirole (0.1 mg/kg, ip) caused a significant alleviation of the akinesia. This effect was significantly reduced by coinjection with the cannabinoid receptor agonist WIN 55,212-2 (0.1 and 0.3 mg/kg). ⋯ The effect of 0.3 mg/kg WIN 55,212-2 on combined D1 and D2 agonist-induced locomotion (0.02 mg/kg) was blocked by SR 141761A (3 mg/kg). Neither WIN 55,212-2 alone (0.1 and 0.3 mg/kg) nor SR 141716A (3 and 30 mg/kg) alone had an antiparkinsonian effect. These results suggest that cannabinoids may modulate neurotransmission in the pathway linking the striatum indirectly to basal ganglia outputs via the lateral globus pallidus and the subthalamic nucleus.