Neuroscience letters
-
Neuroscience letters · Jun 2019
nNOS-PSD95 interactions activate the PKC-ε isoform leading to increased GluN1 phosphorylation and the development of neuropathic mechanical allodynia in mice.
It has been suggested that interactions of neuronal nitric oxide synthase (nNOS) with postsynaptic density 95 (PSD95) play important roles in the development of chronic neuropathic pain. Here we examine the possible role of nNOS-PSD95 interactions in central sensitization as represented by phosphorylation of the NMDA receptor GluN1 subunit (pGluN1) in mice with chronic constriction injury (CCI) of the sciatic nerve. Intrathecal administration of the nNOS-PSD95 interactions inhibitor, IC87201 on post-operative days 0-3 significantly reduced the CCI-induced increase in total NO levels in the lumbar spinal cord dorsal horn. ⋯ Administration of IC87201 significantly inhibited this translocation of PKC-ε, while the expression of PKC-α and -ξ in the cytosol and membrane fractions was unaffected by sciatic nerve injury or injection of IC87201. Furthermore, administration of the PKC-ε inhibitor, εV1-2 on post-operative days 0-3 attenuated the CCI-induced development of MA and pGluN1. Collectively these results demonstrate that spinal nNOS-PSD95 interactions play an important role in PKC-dependent GluN1 phosphorylation via activation of the PKC-ε isoform, and ultimately contributes to the development of MA in peripheral neuropathy.
-
Neuroscience letters · May 2019
PI3K/Akt signaling pathway may be involved in MCP-1-induced P2X4R expression in cultured microglia and cancer-induced bone pain rats.
P2X4 receptor (P2X4R), a subtype of P2 purinergic receptors, is an ATP-gated receptor through which activity of spinal microglia instigates pain hypersensitivity in various pain conditions. Accumulating evidence indicates that monocyte chemoattractant protein-1 (MCP-1) plays an important role in chronic pain facilitation, and it could stimulate microglia activation and involve in regulating P2X4R expression. However, the mechanism of MCP-1 in regulating the expression of P2X4R in microglia is poorly understood, and whether MCP-1 can aggravate pain via up-regulating spinal P2X4R expression in Cancer-induced Bone Pain (CIBP) remains unclear. ⋯ MCP-1 was found to be associated with P2X4R expression and mechanical allodynia induced by CIBP in vivo since the expression of MCP-1 was increased in CIBP and RS-504393 alleviated the P2X4R expression and mechanical allodynia in CIBP. Moreover, RS-504393 also reduced the increase of p-Akt induced by CIBP. Inhibition of PI3K/Akt pathway may partly reduce MCP-1/CCR2-induced expression of P2X4R and mechanical allodynia in CIBP rats.
-
Neuroscience letters · Apr 2019
Neurofilament changes in serum and cerebrospinal fluid after acute ischemic stroke.
Neurofilament light (NFL) is a well-validated biomarker for neuronal injury and neurodegeneration. Increased cerebrospinal fluid (CSF) levels have been shown after stroke, as well as in patients with a broad range of neurodegenerative and neuroinflammatory diseases. Neurofilament heavy (NFH) belongs to the same family of structural proteins but it is less extensively studied. The potential of phosphorylated NFH (pNFH) as a stroke biomarker and for the prediction of clinical outcome is unknown. In this study, we aimed to examine the temporal pattern of NFL and pNFH concentrations in serum and CSF after acute ischemic stroke. ⋯ NFL and pNFH in CSF and serum are promising biomarkers for axonal injury following stroke. Further studies in larger populations are needed to fully understand the progression of the neuronal damage after acute ischemic stroke and to evaluate if these biomarkers can provide additive information and how they relate to outcome.
-
Neuroscience letters · Mar 2019
α-Synuclein in salivary extracellular vesicles as a potential biomarker of Parkinson's disease.
Detection of α-synuclein (α-syn) in biological fluids such as saliva may serve as potential biomarker of PD. α-syn pertaining to extracellular vesicles (EVs) has been recently studied in plasma, but not in other biological fluids such as saliva. ⋯ Exosomes are present in PD saliva. The α-synOlig and α-synOlig/α-synTotal ratio in salivary EVs may serve as potential diagnostic biomarkers for PD.
-
Neuroscience letters · Feb 2019
The involvement of iron responsive element (-) divalent metal transporter 1-mediated the spinal iron overload via CXCL10/CXCR3 pathway in neuropathic pain in rats.
Iron is pivotal for life, but it is toxic if in excess. Iron overload mediated by divalent metal transporter 1 (DMT1) in the central nervous system has participated in various neuroinflammatory diseases. Chemokine-induced neuroinflammation involves the development of pathological pain. Recently, chemokine CXCL10 is implicated in the pathogenesis of chronic pain, however, little is known about the potential link between iron accumulation and CXCL10 in pain condition. Here, we examined whether iron accumulation regulated neuropathic pain via CXCL10. ⋯ Our findings demonstrated the contribution of spinal abnormal iron accumulation in regulating CXCL10 pathway in the pathogenesis of neuropathic pain.