Experimental neurology
-
Experimental neurology · Aug 2001
Comparative StudyBehavioral phenotyping of GFAP-apoE3 and -apoE4 transgenic mice: apoE4 mice show profound working memory impairments in the absence of Alzheimer's-like neuropathology.
For the purpose of studying the potential neurobehavioral effects of different human apolipoprotein E (apoE) isoforms produced within the brain, transgenic (TG) mice were generated in which human apoE3 or apoE4 isoforms were under control of an astrocyte-specific, glial fibrillary acidic protein promoter and these TG mice were bred back to apoE knockout (KO) mice. Behavioral phenotypes of apoE3 and apoE4 TG mice were derived by conducting a longitudinal study in which apoE3 and apoE4 TG mice were compared with apoE KO and wild-type (WT) mice (all male) on several behavioral measures. Analysis of locomotor activity, "open-field" behaviors, acoustic startle/prepulse inhibition, and elevated plus maze data suggested that the apoE TG/KO groups were more "emotionally reactive" than WT mice, with apoE4 mice typically being the most reactive. ⋯ Nonassociative factors (sensorimotor capacities or emotionality differences) did not appear to confound interpretation of the learning/memory results. Western blot analysis revealed no alterations in the level of synaptic, neuronal, or glial markers in neocortex or hippocampus and histologic analysis revealed no evidence of Abeta deposition or neuritic plaques in the apoE KO/TG mice. Our findings suggest that apoE4 expression in the brain may have selective deleterious effects on memory function in the absence of typical Alzheimer's-like neuropathology.
-
Experimental neurology · Aug 2001
N-methyl-D-aspartate receptor blockade during development induces short-term but not long-term changes in c-Jun and parvalbumin expression in the rat cervical spinal cord.
During postnatal development, N-methyl-D-aspartate receptor (NMDA-R) expression progressively decreases in ventral and deep dorsal horns. This transient expression might play a role in activity-dependent development of segmental circuitry. ⋯ However, at P84, MK-801-treated and control spinal cords appeared the same. Therefore, NMDA-R blockade during development only transiently altered expression of activity-dependent proteins in the spinal cord, unlike lesions to the developing motor cortex, which we have previously shown to have a permanent effect.
-
Nociceptive nerves innervate the skin and play an important role in the generation of neuropathic pain. However, it remains elusive whether and how nociceptive nerve terminals degenerate in neuropathic pain conditions. To address this issue, we investigated cutaneous innervation in a model of painful mononeuropathy, the chronic constriction injury (CCI). ⋯ In the skin denervated by tight ligation of the sciatic nerve, epidermal nerves were completely depleted (0 fibers/mm vs. 12.26 +/- 1.44 fibers/mm on the control side, P < 0.001). Animals with tight ligation of the sciatic nerve exhibited thermal anesthesia. These findings suggest that the epidermis is partially denervated in CCI, and that a partial injury of nerves is correlated with the development of neuropathic pain.
-
Experimental neurology · Jul 2001
Pegylated brain-derived neurotrophic factor shows improved distribution into the spinal cord and stimulates locomotor activity and morphological changes after injury.
The neurotrophin brain-derived neurotrophic factor (BDNF) shows promise for the treatment of central nervous system (CNS) trauma and disease. Effective delivery methods are required, however, for BDNF to be useful as a therapeutic agent. To this end, we examined the penetration of intrathecally infused N-terminal pegylated BDNF (peg-BDNF) compared to similar infusion of native BDNF after spinal cord injury (SCI). ⋯ The infusion of peg-BDNF, regardless of the timing of delivery, was related to enhanced sprouting of putative cholinergic fibers, like that observed after high dose native BDNF treatment. Despite improved delivery, however, neither axonal responses nor the extent of locomotor recovery were enhanced compared to native BDNF treatment. This suggests that alternative strategies, such as neurotrophin treatment in conjunction with cell transplantation techniques, or treatment nearer the cell bodies of target neurons might be employed in an attempt to effect significant repair after SCI.
-
Experimental neurology · Jul 2001
Phosphorylation of signal transducer and activator of transcription-3 (Stat3) after focal cerebral ischemia in rats.
JAK-STAT is the major downstream signal pathway of interleukin-6 (IL-6) cytokine family and is regulated by Tyr705 phosphorylation of Stat3. The present study examined the extent and the localization of phosphorylated Stat3 protein in brain tissue after focal ischemia in rats. The localizations of unphosphorylated and phosphorylated Stat3 were immunohistochemically examined in rats after 0.5 to 168 h of reperfusion following 1.5 h of middle cerebral artery occlusion (MCAO), induced by the intraluminal suture method. ⋯ Double-staining immunohistochemistry with these cellular makers revealed phosphorylated Stat3 to be present in neurons, but in neither astrocytes nor microglia/macrophages. These results were also confirmed be western blot analysis. The present results indicate that Stat3 activation occurs in neurons and endothelial cells only during post-ischemic reperfusion despite widespread expression of IL-6 cytokines.