Neuroscience
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Comparative Study
Dendritic morphogenesis of cerebellar Purkinje cells through extension and retraction revealed by long-term tracking of living cells in vitro.
Cerebellar Purkinje cells have the most elaborate dendritic trees among the neurons in the CNS. To investigate the dynamic aspects of dendritic morphogenesis of Purkinje cells, we performed a long-term analysis of living cells in cerebellar cell cultures derived from glutamate decarboxylase 67-green fluorescent protein mice. Most Purkinje cells had several primary dendrites during the 25-day culture period. ⋯ Furthermore, treatment with an inhibitor of calcium/calmodulin-dependent protein kinase II reduced the number of primary dendrites specifically during 5-15 days in vitro, the culture period when the extension and retraction of primary dendrites occurred actively. Blockade of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid/kainate-type glutamate receptors also reduced the number of primary dendrites during the same culture period, while inhibition of glutamate transporters increased the number. These findings suggest that the final morphology of Purkinje cells is achieved not only through extension, but also through retraction of their dendrites, and that calcium/calmodulin-dependent protein kinase II and neuronal activity are involved in this dendritic morphogenesis.
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Comparative Study
Role of interleukin-6 in lipopolysaccharide-induced brain injury and behavioral dysfunction in neonatal rats.
There are increasing data in support of the hypothesis that inflammatory cytokines are involved in neonatal white matter damage. Despite extensive study of the proinflammatory cytokines tumor necrosis factor-alpha and interleukin-1beta, the role of interleukin-6 in the development of white matter damage is largely unknown. In the present study, the role(s) of interleukin-6 in mediating lipopolysaccharide-induced brain injury and behavioral changes was investigated by the intracerebral injection of lipopolysaccharide with interleukin-6 neutralizing antibody in the 5-day-old rat brain. ⋯ However, no changes of tumor necrosis factor-alpha and interleukin-1beta were detected. In contrast, no histopathological changes and glial activation were observed in rats injected with only interleukin-6. The present study indicates that the contribution to brain injury by interleukin-6 depends on its interaction with other lipopolysaccharide-induced agents and not on interleukin-6 alone.
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Comparative Study
C fragment of tetanus toxin hybrid proteins evaluated for muscle-specific transsynaptic mapping of spinal motor circuitry in the newborn mouse.
We investigated whether the non-toxic C fragment of tetanus toxin (TTC) fused to either beta-galactosidase or green fluorescent protein could be utilized to transsynaptically trace muscle-specific spinal circuitry in the neonatal mouse after i.m. injection into a single hindlimb muscle. We found that even with careful low volume injection (0.2-1.0 microl) into a single muscle (medial gastrocnemius), the TTC hybrid proteins spread rapidly to many other hindlimb muscles and to trunk musculature such that retrograde labeling of motoneurons could not be constrained to a single motoneuron pool. Retrogradely labeled motoneurons in the lower lumbar segments harboring the medial gastrocnemius motoneuron pool were first observed two hours after the medial gastrocnemius injection. ⋯ TTC injection procedure described here therefore provides an important tool for the study of presynaptic terminals onto motoneurons. However, additional technical modifications will be required to utilize TTC tracers for transsynaptic mapping of muscle-specific spinal motor circuitry in the neonatal mouse. We provide here a set of criteria for assessing the i.m. delivery of TTC tracers as a basis for future improvements in this technique.
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Comparative Study
Possible sources and sites of action of the nitric oxide involved in synaptic plasticity at spinal lamina I projection neurons.
The synaptic long-term potentiation between primary afferent C-fibers and spinal lamina I projection neurons is a cellular model for hyperalgesia [Ikeda H, Heinke B, Ruscheweyh R, Sandkühler J (2003) Synaptic plasticity in spinal lamina I projection neurons that mediate hyperalgesia. Science 299:1237-1240]. In lamina I neurons with a projection to the periaqueductal gray, this long-term potentiation is dependent on nitric oxide. ⋯ Synthesis of cyclic 3',5'-guanosine monophosphate upon stimulation by a nitric oxide donor confirmed the presence of active guanylyl cyclase in at least a portion of the spino-periaqueductal gray neuronal cell bodies. We therefore propose that nitric oxide generated in neighboring neurons or blood vessels acts on the spino-periaqueductal gray neuron and/or the primary afferent C-fiber to enable long-term potentiation. Lamina I spino-parabrachial neurons were stained for comparison and yielded similar results.
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Comparative Study
Sensory system-predominant distribution of leukotriene A4 hydrolase and its colocalization with calretinin in the mouse nervous system.
Leukotriene B4 is a potent lipid mediator, which has been identified as a potent proinflammatory and immunomodulatory compound. Although there has been robust evidence indicating that leukotriene B4 is synthesized in the normal brain, detailed distribution and its functions in the nervous system have been unclear. To obtain insight into the possible neural function of leukotriene B4, we examined the immunohistochemical distribution of leukotriene A4 hydrolase, an enzyme catalyzing the final and committed step in leukotriene B4 biosynthesis, in the mouse nervous system. ⋯ The ubiquitous distribution of leukotriene A4 hydrolase was in sharp contrast with the distribution of leukotriene C4 synthase [Shimada A, Satoh M, Chiba Y, Saitoh Y, Kawamura N, Keino H, Hosokawa M, Shimizu T (2005) Highly selective localization of leukotriene C4 synthase in hypothalamic and extrahypothalamic vasopressin systems of mouse brain. Neuroscience 131:683-689] which was confined to the hypothalamic and extrahypothalamic vasopressinergic neurons. These results suggest that leukotriene B4 may exert some neuromodulatory function mainly in the sensory nervous system, in concert with calretinin.