Journal of neuroscience research
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Channel properties and synaptic targeting of N-methyl-D-aspartate (NMDA) receptors determine their importance in synaptic transmission, long-term synaptic plasticity, and developmental reorganization of synaptic circuits. To investigate the involvement of the C-terminal domain of the NR2B subunit in regulating channel properties and synaptic localization, we analyzed gene-targeted mice expressing C-terminally truncated NR2B subunits (NR2B(DeltaC/DeltaC) mice; Sprengel et al. [1998] Cell 92:279-89). Because homozygous NR2B(DeltaC/DeltaC) mice die perinatally, we studied embryonic neocortical neurons differentiating in culture. ⋯ In neurons from NR2B(DeltaC/DeltaC) mice, the synaptic NMDA receptor fraction was drastically reduced, suggesting that the C-terminal domain of the NR2B subunit plays a major role in synaptic targeting of NMDA receptors at nascent synapses. With increasing time in culture, the reduction in NMDA EPSCs in neurons from NR2B(DeltaC/DeltaC) mice diminished. This is explained by the expression of additional NMDA receptor subtypes containing NR2A subunits at more mature synapses.
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This study investigated the feasibility of using a peripheral nerve autograft (NAG) to promote and guide regeneration of sensory axons from the caudal lumbar dorsal roots to the rostral dorsal column following a lower thoracic cordotomy in adult rats. After a left hemicordotomy at the T13 vertebra level and ipsilateral L3 and L4 rhizotomies, a peripheral NAG (peroneal nerve) was connected to the distal roots stumps, then implanted into the left dorsal column 10 mm rostral to hemicordotomy site (n = 12). After surgery, all animals of the experimental group experienced complete anesthesia in their left hindlimb. ⋯ Histological analysis of the NAG showed evidence of axonal regeneration in all 8 animals with positive retrograde labeling of DRG neurons. However, we did not find a statistical correlation between the number of HRP-stained neurons and the degree of sensory recovery. This study demonstrates that an NAG joining dorsal roots to the dorsal column, thus shunting the original CNS-PNS junction, can support regeneration of central axons from DRG primary sensory neurons into the dorsal column over distances of at least 30 mm despite the inhibitory influence of the CNS white matter.
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Comparative Study
Varied actions of proinflammatory cytokines on excitotoxic cell death in the rat central nervous system.
Interleukin (IL)-1beta mediates diverse forms of neurodegeneration and exacerbates cell death induced by striatal injection of the excitotoxin alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) in the rat brain. The objective of this study was to determine whether this effect was specific to IL-1beta. ⋯ These findings suggest that the effect of IL-1 on AMPA receptor-mediated cell death in the rat striatum is not mimicked by other proinflammatory cytokines. Furthermore, TNFalpha shows neuroprotective effects against acute excitotoxic injury.
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After target ablation by olfactory bulbectomy (OBX), the murine olfactory epithelium (OE) undergoes degenerative changes leading to apoptosis of olfactory receptor neurons (ORNs) followed by regenerative changes that include proliferation of progenitor cells leading to neurogenesis and ORN replacement. Macrophages recruited to the OE after OBX are involved in both the degenerative and regenerative processes. Relative quantitative RT-PCR was used to demonstrate that within hours of OBX, mRNAs encoding three key components in the leukemia inhibitory factor (LIF) signaling pathway, including LIF, LIF receptor (LIFR), and STAT3, as well as cyclin D1, a growth factor sensor indicative of progenitor cell transformation, were upregulated. ⋯ LIF mRNA was localized in infiltrating macrophages; near-adjacent sections exhibited macrophages immunoreactive for F4/80, a marker for activated macrophages, in numbers commensurate with those expressing LIF mRNA. LIF mRNA was also localized in surviving ORNs, identified by their expression of olfactory marker protein (OMP) mRNA and protein in near-adjacent sections. Our data suggest that LIF functions as a mitogen originating from recruited macrophages through an intercellular signaling pathway that stimulates proliferation of progenitor cells leading to neurogenesis and regeneration, and as an intracellular survival factor for traumatized ORNs.
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Slow antigravity muscles differ from fast muscles with regard to load bearing performed during contraction. We examined the importance of load bearing in regulation of acetylcholinesterase (AChE) expression in slow and fast rat muscles. The levels of AChE mRNA in the slow soleus muscles are about 30% of those in the fast extensor digitorum longus (EDL) muscles. ⋯ The levels observed after phasic stimulation were significantly higher than those after low-frequency tonic stimulation, indicating the importance of muscle activation pattern for AChE regulation also in the absence of load bearing. The AChE mRNA levels in the soleus muscles overloaded for 8 days by synergist muscle ablation increased significantly to about 50% of those in the EDL muscle. The load bearing during muscle contraction seems to be a relatively unimportant extrinsic factor in the regulation of the AChE mRNA levels in muscle fibers, except when an increased load induces muscle hypertrophy accompanied by the fusion of satellite cells with the muscle fibers.