Journal of neuroscience research
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Although alterations in adenylate cyclase (AC) activity and somatostatin (SRIF) receptor density have been reported in Alzheimer's disease, the effects of amyloid beta-peptide (Abeta) on these parameters in the hippocampus are unknown. Our aim was to investigate whether the peptide fragment Abeta(25-35) can affect the somatostatinergic system in the rat hippocampus. Hence, Abeta(25-35) was injected intracerebroventricularly (i.c.v.) to Wistar rats in a single dose or infused via an osmotic minipump connected to a cannula implanted in the right lateral ventricle during 14 days. ⋯ Furthermore, the protein levels of the neural-specific AC type I were significantly decreased in the hippocampus of the treated rats, whereas an increase in the levels of AC V/VI was found, with no alterations in type VIII AC. A single i.c.v. dose of Abeta(25-35) exerted no effect on SRIF content or SRIF receptors but induced a slight decrease in forskolin-stimulated AC activity and its inhibition by SRIF. Because chronic Abeta(25-35) infusion impairs learning and memory whereas SRIF facilitates these functions, the alterations described here might be physiologically important given the decreased cognitive behavior previously reported in Abeta-treated rats.
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Neuronkinin-1 receptor (NK-1R), the neuropeptide substance P (SP) preferring receptor, is highly expressed in areas of the central nervous system (CNS) that are especially implicated in depression, anxiety, and stress. Repeated exposure to opioids may sensitize neuronal systems involved in stress response. We examined the effects of morphine, the principal metabolite of heroin, on the functional expression of NK-1R in the cortical neurons. ⋯ Blocking opioid receptors on the cortical neurons by naltrexone or CTAP (a mu-opioid receptor antagonist) abolished the morphine action. Investigation of the mechanism(s) responsible for the morphine action showed that morphine activated NK-1R promoter and induced the phosphorylation of p38 MAPK protein in the cortical neurons. These in vitro data provide a plausible cellular mechanism for opioid-mediated neurological disorders.
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Comparative Study
Neuroprotective effect of N-acetylcysteine on neuronal apoptosis induced by a synthetic gingerdione compound: involvement of ERK and p38 phosphorylation.
Besides being used as a spice, ginger has been applied in oriental medicine to ameliorate symptoms such as inflammatory, rheumatic disorders, and gastrointestinal discomforts. The effects of ginger on neuronal cells, however, have not been explored. We investigate the effect of 1-(3,4-dimethoxyphenyl)-3,5-dodecenedione (I(6)), a derivative of gingerdione, on cultured cortical neurons. ⋯ Unexpectedly, NAC also increased phosphorylated level of p38 mitogen-activated protein kinase (MAPK) and p38 specific inhibitors dose-dependently attenuated the effect of NAC. Farnesyltransferase and MEK inhibitors completely abolished NAC-induced p38 phosphorylation whereas p38 inhibitor did not influence NAC-induced ERK phosphorylation. These results show that NAC serially activates ERKs and p38 MAPK, and ERKs and p38 work together to mediate the neuroprotective effect of NAC.
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It is well known that peripheral sensory stimuli, including pain, trigger a series of neuronal activities along the somatosensory pathways as well as the neuronal network in the high brain structures. These neuronal activities not only produce appropriate physiological responses but also induce long-term plastic changes in some of the central synapses. It is believed that long-term synaptic changes help the brain to process and store new information. ⋯ In the case of permanent injury, however, the brain fails to distinguish the difference between "useful" and painful stimuli. Long-term synaptic changes work against the system and at least in part contribute to chronic pain. In this short article, the possible molecular mechanisms for long-term plasticity within the anterior cingulate cortex (ACC) will be discussed and reviewed, and it is hypothesized that potentiation of excitatory responses within the ACC contributes to chronic pain and pain-related mental disorders.
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Comparative Study
Role of phosphorylation of ERK in induction and maintenance of LTP of the C-fiber evoked field potentials in spinal dorsal horn.
Previous works have shown that activation of extracellular signal-regulated kinase (ERK)/cAMP response element binding protein (CREB) pathway is essential for long-term potentiation (LTP) in hippocampus. In the present study, the role of the ERK/CREB pathway in LTP of C-fiber evoked field potentials in spinal dorsal horn, which is relevant to pathologic pain, was investigated in adult rats. Western blotting analysis showed that the protein level of phosphorylated ERK (p-ERK) in ipsilateral spinal dorsal horn was transiently increased after LTP induction, starting at 15 min and returning to control at 60 min after tetanic stimulation and that the protein level of p-CREB increased at 30 min, persisting for at least 3 hr after LTP induction. ⋯ When applied 15 min after LTP induction, PD98059 reversed established LTP. The drug, however, did not affect the spinal LTP, when applied at 30 min after LTP. Our results suggested that activation of ERK/CREB pathway in spinal dorsal neurons is necessary for induction and maintenance of long-term potentiation of the C-fiber evoked field potentials.