Journal of neuroscience research
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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.