Neuroscience letters
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Neuroscience letters · May 2014
CNTF regulates neurite outgrowth and neuronal migration through JAK2/STAT3 and PI3K/Akt signaling pathways of DRG explants with gp120-induced neurotoxicity in vitro.
HIV envelope glycoprotein gp120 is highly involved in HIV infection-related peripheral neuropathy, but its mechanism remains incompletely understood. The therapy of this neuropathy is still a big clinical challenge for neurologists. The organotypically cultured dorsal root ganglion (DRG) explants were used to test the neurotoxic actions of gp120 and the therapeutic effects of ciliary neurotrophic factor (CNTF) on gp120-induced neurotoxicity. ⋯ Either Janus kinase 2 (JAK2) inhibitor AG490 or phosphatidyl inositol-3'-phosphate-kinase (PI3K) inhibitor LY294002 blocked the effects of CNTF. These data imply that CNTF improved neuronal status by promoting GAP-43 expression and inhibiting apoptosis through JAK2/signal transducer and activator of transcription 3 (STAT3) and PI3K/Akt signaling pathways of DRG neurons with gp120-induced neurotoxicity. These data offered a new clue for elucidating the mechanisms of HIV infection-related peripheral neuropathy and facilitating the development of novel therapy.
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Neuroscience letters · May 2014
Satellite glial cells in dorsal root ganglia are activated in experimental autoimmune encephalomyelitis.
Pain is a serious and common problem with patients suffering from multiple sclerosis (MS). Very little has been done to investigate the peripheral mechanisms of pain in MS. ⋯ We examined dorsal root ganglia and found increased expression of glial fibrillary acidic protein in SGCs, a marker of SGC activation, and increased coupling among SGCs, a known component of activated SGCs. Activated SGCs have previously been shown to contribute to pain in other classical neuropathic pain models, suggesting that pain in multiple sclerosis has a peripheral component.
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Neuroscience letters · May 2014
Distinct role of tumor necrosis factor receptor subtypes 1 and 2 in the red nucleus in the development of neuropathic pain.
Previous studies have demonstrated that tumor necrosis factor-alpha (TNF-α) in the red nucleus (RN) plays a facilitated role in the development of neuropathic pain. Here, the protein levels and roles of two different TNF receptors, p55 type 1 (TNFR1) and p75 type 2 (TNFR2), in the RN of rats with spared nerve injury (SNI) were investigated. Immunohistochemistry demonstrated that both TNFR1 and TNFR2 were significantly increased in the RN of rats with SNI compared with sham-operated and normal rats. ⋯ Combined injection of anti-TNFR1-Ab and anti-TNFR2-Ab (500ng for each antibody) into the RN generated a relatively faster and longer analgesic effect compared with single using of anti-TNFR1-Ab or anti-TNFR2-Ab. These results support that TNF-α in the RN plays a crucial role in regulating neuropathic pain, and suggest that the algesic effect of TNF-α is transmitted through both TNFR1 and TNFR2. TNFR1 has equally important role in the early development and later maintenance of neuropathic pain, while TNFR2 is more inclined to play a role in the early development of neuropathic pain.
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Neuroscience letters · May 2014
Antidepressant activity in mice elicited by 3-furan-2-yl-N-p-tolyl-acrylamide, a positive allosteric modulator of the α7 nicotinic acetylcholine receptor.
The objective of the current study is to determine whether 3-furan-2-yl-N-p-tolyl-acrylamide (PAM-2), a positive allosteric modulator of α7 nicotinic receptors (AChRs), produces antidepressant-like behavior in mice, and reactivates desensitized α7 AChRs expressed in CH3-α7 cells. Mice from both sexes were injected (i.p.) with PAM-2 (1.0mg/kg) on a daily basis for three weeks. Forced swim tests (FSTs) were performed on Day 1 and Day 7 to determine the acute and subchronic effects of PAM-2, respectively, and on Days 14 and 21 to determine its chronic activity. ⋯ Since PAM-2 does not influence the locomotor activity of mice, the observed antidepressant activity is not driven by nonspecific motor-stimulant actions, (3) the residual antidepressant effect mediated by PAM-2 after one week of treatment cessation is observed only in female mice, and finally the Ca(2+) influx results indicate that (4) PAM-2 can reactivate desensitized α7 AChRs. Our results clearly indicate that PAM-2 elicits antidepressant activity, probably by enhancing the activity of the endogenous neurotransmitter acetylcholine on α7 AChRs, without inducing receptor desensitization, and that this activity is gender-dependent. This is the first time that an antidepressant activity is described for an α7 PAM, supporting further studies as potential therapeutic medications for depressive states.
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Neuroscience letters · May 2014
The analgesia effect of duloxetine on post-operative pain via intrathecal or intraperitoneal administration.
One promising strategy to prevent the chronicity of post-operative pain (POP) is to attenuate acute POP during the early phase by efficacious medications with fewer side effects. Duloxetine, one of the serotonin (5-HT)-norepinephrine (NE) reuptake inhibitors (SNRI), is used to treat a wide range of acute and chronic pain. However, its effect on POP has not been investigated. ⋯ The anti-hypersensitivity effect of duloxetine was partly attenuated by pretreatment with ketanserin or idazoxane. Microdialysis study revealed that 5-HT and NA concentrations at the spinal dorsal horn were increased, peaking at 30min after i.p. injection of 20mg/kg duloxetine. These findings indicate that duloxetine inhibits POP by increasing spinal NA and 5-HT levels and activating spinal 5-HT2A or α2-noradrenergic receptors.