Neuroscience
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Following transection of the spinal cord, severed axonal ends retract from the lesion site and attempt regeneration within 24 h of injury. Molecular mechanisms underlying such rapid axonal reactions after severance are not fully characterized so far. To better understand the early axonal degenerating and regenerating processes, we examined the immunohistological expression of axonal cytoskeletal proteins from 5 min to 48 h after scalpel-transection of adult rat spinal cord white matter. ⋯ These observations indicate that adult rat cordotomy with a scalpel results in the rapid formation of intensely NF-IR-positive zipper-like axon segments at the transection site, which are similar to "preserved fibers" reported by Ramon y Cajal [Ramon y Cajal S (1928) Degeneration and regeneration in the nervous system. New York: Hafner]. On the other hand, axonal regenerative responses start within 6 h of injury, which may be supported by calpain-activation and intra-axonal protein synthesis.
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The rewarding effects of cocaine have been reported to occur within seconds of administration. Extensive evidence suggests that these actions involve the ability of cocaine to inhibit the dopamine (DA) transporter. We recently showed that 1.5 mg/kg i.v. cocaine inhibits DA uptake within 5 s. ⋯ Further, the blood-brain barrier impermeant cocaine-methiodide had no effect on DA uptake or peak height, indicating that the generalized peripheral effects of cocaine do not contribute to the CNS alterations measured here. Finally, we show that GBR-12909 (0.75, 1.5, and 3.0 mg/kg) also significantly inhibited DA uptake within 5 s post-injection, although the peak effect and return to baseline were markedly delayed compared with cocaine, particularly at the highest dose. Combined, these observations indicate that the central effects of dopamine uptake inhibitors occur extremely rapidly following i.v. drug delivery.
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Previously, we reported that the stress associated with chronic isolation was associated with increased beta-amyloid (Abeta) plaque deposition and memory deficits in the Tg2576 transgenic animal model of Alzheimer's disease (AD) [Dong H, Goico B, Martin M, Csernansky CA, Bertchume A, Csernansky JG (2004) Effects of isolation stress on hippocampal neurogenesis, memory, and amyloid plaque deposition in APP (Tg2576) mutant mice. Neuroscience 127:601-609]. In this study, we investigated the potential mechanisms of stress-accelerated Abeta plaque deposition in this Tg2576 mice by examining the relationship between plasma corticosterone levels, expression of glucocorticoid receptor (GR) and corticotropin-releasing factor receptor-1 (CRFR1) in the brain, brain tissue Abeta levels and Abeta plaque deposition during isolation or group housing from weaning (i.e. 3 weeks of age) until 27 weeks of age. ⋯ Furthermore, the expression of CRFR1 was increased in isolated Tg+ mice, but decreased in isolated Tg- mice in both cortex and hippocampus. Changes in the components of hypothalamic-pituitary-adrenal (HPA) axis were accompanied by increases in brain tissue Abeta levels and Abeta plaque deposition in the hippocampus and overlying cortex in isolated Tg+ mice. These results suggest that isolation stress increases corticosterone levels and GR and CRFR1 expression in conjunction with increases in brain tissue Abeta levels and Abeta plaque deposition in the Tg2576 mouse model of AD.
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Long term facilitation (LTF) of C-fiber-evoked firing of wide dynamic range neurons in the spinal dorsal horn in response to conditioning stimulation (CS) of afferent fibers is a widely studied cellular model of spinal nociceptive sensitization. Although 100 Hz CS of primary afferent fibers is commonly used to induce spinal cord LTF, this frequency exceeds the physiological firing range. Here, we examined the effects of electrical stimulation of the sciatic nerve within the physiological frequency range on the magnitude and stability of the C-fiber-evoked responses of wide dynamic range neurons and the expression of immediate early genes (c-fos, zif268, and Arc) in anesthetized rats. ⋯ Three hertz stimulation induced the early phase of LTF, but the responses were decremental. Arc and zif268, two genes previously coupled to LTP of synaptic transmission in the adult brain, are upregulated at the same frequencies that give stable LTF (30 and 100 Hz). This frequency-dependence is important for understanding how the afferent firing pattern affects neuronal plasticity and nociception in the spinal dorsal horn.
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We report naturally occurring, systematic variations in synaptic strength at neuromuscular junctions along the dorsal-ventral (D-V) axis of the Drosophila larval body wall. These gradual changes were correlated with differences in presynaptic neurotransmitter release regulated by nerve terminal excitability and in postsynaptic receptor composition influencing miniature excitatory junctional potential (mEJP) amplitude. Surprisingly, synaptic strength and D-V differentials at physiological Ca(2+) levels were not significantly altered in slowpoke (slo) and Shaker (Sh) mutants, despite their defects in two major repolarizing forces, Ca(2+)-activated Slo (BK) and voltage-activated Sh currents, respectively. ⋯ In addition, slo mutants displayed altered immunoreactivity intensity ratio between DGluRIIA and DGluRIIB receptor subunits. This modified receptor composition caused smaller mEJP amplitudes, further preventing excessive transmission in the absence of Slo current. Such compensatory regulations were prevented by rutabaga (rut) adenylyl cyclase mutations in rut slo double mutants, demonstrating a novel role of rut in homeostatic plasticity, in addition to its well-established function in learning behavior.