Neuroscience
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It was recently reported that glia cell line-derived neurotrophic factor (GDNF) facilitates presynaptic axonal growth and neurotransmitter release at neuromuscular synapses. Little is known, however, whether GDNF can also act on the postsynaptic apparatus and its underlying mechanisms. Using biochemical cold blocking of existing membrane acetylcholine receptors (AchRs) and biotinylation of newly inserted receptors we demonstrate that GDNF increases the insertion of AChRs into the surface membrane of mouse primary cultured muscle cells and that this does not require protein synthesis. ⋯ GDNF may signal through c-Ret as well as NCAM-140 pathways since both the signaling receptors are expressed in the neuromuscular junction (NMJ). These data suggest that GDNF is an autocrine regulator of NMJ to promote the insertion and stabilization of postsynaptic AchRs. In vivo, GDNF may function as a synaptotrophic modulator for both pre- and postsynaptic differentiation to strengthen the functional and structural connections between nerve and muscle, and contribute to the synaptogenesis and plasticity of neuromuscular synapses.
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Comparative Study
Effects of fimbria-fornix transection on calpain and choline acetyl transferase activities in the septohippocampal pathway.
The ability of fimbria-fornix bilateral axotomy to elicit calpain and caspase-3 activation in the rat septohippocampal pathway was determined using antibodies that selectively recognize either calpain- or caspase-cleaved products of the cytoskeletal protein alphaII-spectrin. Radioenzymatically determined choline acetyl transferase (ChAT) activity was elevated in the septum at day 5, but reduced in the dorsal hippocampus at days 3, 5 and 7, after axotomy. Prominent accumulation of calpain-, but not caspase-3-, cleaved spectrin proteolytic fragments was observed in both the septum and dorsal hippocampus 1-7 days after axotomy. ⋯ Accumulation of calpain-cleaved spectrin proteolytic fragments in the dorsal hippocampus and septum at day 5 after axotomy was reduced by i.c.v. administration of two calpain inhibitors. Calpain inhibition partially reduced the elevation of ChAT activity in the septum produced by transection but failed to decrease the loss of ChAT activity in the dorsal hippocampus following axotomy. These findings suggest that calpain activation contributes to the cholinergic cell body response and hippocampal axonal cytoskeletal degradation produced by transection of the septohippocampal pathway.
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Comparative Study
Allopregnanolone and progesterone decrease cell death and cognitive deficits after a contusion of the rat pre-frontal cortex.
We compared the effects of three different doses of allopregnanolone (4, 8 or 16 mg/kg), a metabolite of progesterone, to progesterone (16 mg/kg) in adult rats with controlled cortical impact to the pre-frontal cortex. Injections were given 1 h, 6 h and every day for 5 consecutive days after the injury. ⋯ On that same day the injured rats treated with progesterone showed more weight gain compared with the injured rats treated with the vehicle. These results can be taken to show that progesterone and allopregnanolone have similar neuroprotective effects after traumatic brain injury, but allopregnanolone appears to be more potent than progesterone in facilitating CNS repair.
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Systemic administration of a cannabinoid agonist produces antinociception through the activation of pain modulating neurons in the rostral ventromedial medulla (RVM). The aim of the present study was to determine how a cannabinoid receptor agonist acting directly within the RVM affects neuronal activity to produce behaviorally measurable antinociception. In lightly anesthetized rats, two types of RVM neurons have been defined based on changes in tail flick-related activity. ⋯ Furthermore, 2.0 microg/microl WIN55,212-2 delayed the onset of the off-cell pause and increased tail flick latencies. Microinfusion of WIN55,212-2 to brain regions caudal or lateral to the RVM had no effect on RVM neuronal activity or tail flick latencies. These results indicate that cannabinoids act directly within the RVM to affect off-cell activity, providing one mechanism by which cannabinoids produce antinociception.
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Comparative Study
Corticotropin-releasing factor receptor type 1 and 2 mRNA expression in the rat anterior pituitary is modulated by intermittent hypoxia, cold and restraint.
We had previously demonstrated that continual-hypoxia stimulated corticotropin-releasing factor (CRF)mRNA in hypothalamus, and release of CRF, as well as enhancing plasma adrenocorticotropic-hormone and corticosterone of rats. The present study demonstrates using in situ autoradiography that CRF receptor 1 (CRFR1) and CRF receptor 2 (CRFR2) mRNA in the rat anterior pituitary is changed by intermittent hypoxia, cold, restraint, alone and in combination. Rats were exposed to intermittent hypoxia for 4 h/day during various periods in a hypobaric chamber. ⋯ These results show that the acute response to intermittent hypoxia is a decrease in the CRF receptor mRNA whereas longer exposure to the three environmental stressors hypoxia, cold and restraint is needed to provoke an increase. This may have important consequences for adaptation to high altitude. The significant differences between the expression of CRFR1 mRNA and CRFR2 mRNA in response to the different stimuli might suggest that the two receptors in the pituitary play different roles in behavior.