Neuroscience letters
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Neuroscience letters · Apr 2016
Z-guggulsterone negatively controls microglia-mediated neuroinflammation via blocking IκB-α-NF-κB signals.
Induction of pro-inflammatory factors is one of the characteristics of microglial activation and can be regulated by numerous active agents extracted from plants. Suppression of pro-inflammatory factors is beneficial to alleviate neuroinflammation. Z-guggulsterone, a compound extracted from the gum resin of the tree commiphora mukul, exhibits numerous anti-inflammatory effects. ⋯ These major findings were ascertained in primary microglia where the LPS-induced increases in iNOS expression, NO content, and IκB-α degradation were diminished by Z-guggulsterone treatment. In a mouse model of neuroinflammation, Z-guggulsterone exhibited significant anti-inflammatory effects, which were exemplified by the attenuation of microglial activation and neuroinflammation-induced behavioral abnormalities in Z-guggulsterone-treated mice. Taken together, these studies demonstrate that Z-guggulsterone attenuates the LPS-mediated induction of pro-inflammatory factors in microglia via inhibition of IκB-α-NF-κB signals, providing evidence to uncover the potential role of Z-guggulsterone in neuroinflammation-associated disorder therapies.
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Neuroscience letters · Apr 2016
Mas-related gene (Mrg) C receptors inhibit mechanical allodynia and spinal microglia activation in the early phase of neuropathic pain in rats.
Mas-related gene (Mrg) C receptors are exclusively expressed in the trigeminal and dorsal root ganglia (DRG). However, their functional roles are poorly understood. This study was aimed to determine the effect of MrgC receptors on pain hypersensitivity in the early phase of neuropathic pain and its underlying mechanisms. ⋯ On the other hand, SNL, but not sham, surgery reduced the expression of MrgC receptor mRNA in the injured L5 DRG without changing thier levels in the adjacent uninjured L4 or L6 DRG on day 2 following the surgery. These results suggest that the activation of MrgC receptors can relieve pain hypersensitivity by the inhibition of nNOS increase in DRG neurons and microglia activation in the spinal dorsal horn in the early time following peripheral nerve injury. This study provides evidence that MrgC receptors could be targeted as a novel therapy for neuropathic pain with limited unwanted effects.
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Neuroscience letters · Apr 2016
Propofol, but not etomidate, increases corticosterone levels and induces long-term alteration in hippocampal synaptic activity in neonatal rats.
Animal studies provide strong evidence that general anesthetics (GAs), administered during the early postnatal period, induce long-term cognitive and neurological abnormalities. Because the brain growth spurt in rodents is delayed compared to that in humans, a fundamental question is whether the postnatal human brain is similarly vulnerable. Sevoflurane and propofol, GAs that share positive modulation of the gamma-aminobutyric acid type A receptor (GABAAR) function cause marked increase in corticosterone levels and induce long-term developmental alterations in synaptic activity in rodents. ⋯ Only propofol caused a significant increase in serum corticosterone levels (F(4.26)=17.739, P<0.001). In contrast to increased frequency of mIPSCs in the propofol group (F(4.23)=8.731, p<0.001), mIPSC activity in the etomidate group was not different from that in the vehicle groups. The results of this study together with previously published data suggest that anesthetic-caused increase in corticosterone levels is required for GABAergic GAs to induce synaptic effects in the form of a long-term increase in the frequency of hippocampal mIPSCs.
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Neuroscience letters · Mar 2016
Microglial polarization dynamics in dorsal spinal cord in the early stages following chronic sciatic nerve damage.
Peripheral nerve injury can lead to activation of spinal microglia, which can mediate neuroinflammation and contribute to neuropathic pain following nerve injury. Activated microglia may manifest with either pro-inflammatory M1 phenotype or anti-inflammatory M2 phenotype, which may lead to detrimental or beneficial roles in the nervous system. In this study, microglia numbers, morphology and gene profiles were examined in the dorsal spinal cord of rats over 14 days following sciatic nerve chronic constriction injury (CCI). ⋯ Neuropathic pain developed within seven to 14 days following injury and microglia numbers were increased, with almost all in the dorsal spinal cord morphologically defined as activated. At day one after CCI, both M1 and M2 microglia-related genes were increased but only M1 microglia-related genes remained elevated at day seven and 14 thereafter. These results indicate that both M1 and M2 microglia were activated in the dorsal spinal cord one day after CCI but the microglia skewed towards M1 phenotype during the following seven and 14 days.
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Neuroscience letters · Mar 2016
Ventral tegmental area muscarinic receptors modulate depression and anxiety-related behaviors in rats.
Cholinergic and dopaminergic mechanisms within the mesolimbic dopamine system are suggested to play a role in the manifestation of depression and anxiety-related disorders. However, despite the fact that cholinergic mechanisms in the ventral tegmental area (VTA) highly regulate dopamine activity, the role of VTA cholinergic mechanisms in depression-related behaviors is relatively unknown. Here we sought to determine whether enhancing cholinergic tone in the VTA would alter depression and anxiety-related behavior in the forced swim test (FST), elevated plus maze (EPM) and sucrose preference test (SPT). ⋯ Similar to physostigmine, VTA infusion of the muscarinic receptor agonist, pilocarpine (0, 3, 30μg/side), increased immobility time in the FST and decreased time spent on open arms in the EPM. These data suggest that enhanced VTA cholinergic tone promotes pro-depressive and anxiogenic-like effects and demonstrate that specific activation of VTA muscarinic receptors is also sufficient to induce pro-depressive and anxiogenic responses. Together, these findings reveal a novel role of VTA cholinergic, and specifically muscarinic receptor, mechanisms in mediating responses to stress and anxiety.