Neurochemical research
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Neurochemical research · Oct 2008
Involvement of spinal somatostatin receptor SST(2A) in inflammation-induced thermal hyperalgesia: ultrastructural and behavioral studies in rats.
Our previous results have shown that somatostatin receptor subtype SST(2A) is responsible for thermal, but not mechanical nociceptive transmission in the rat spinal cord. The present study was undertaken to further examine the ultrastructural localization of SST(2A) receptor in lamina II of the spinal dorsal horn and the role of SST(2A) receptor in thermal hyperalgesia following Complete Freund's Adjuvant (CFA)-induced inflammation. We found that SST(2A) receptors in lamina II are located primarily in postsynaptic dendrites and soma, but not in axons or synaptic terminals. ⋯ Intrathecal application of SST(2A) agonist SOM-14 at different doses prior to CFA treatment did not influence thermal hyperalgesia in inflamed rats, but at a low dose shortened PWL evoked by noxious heating in normal rats. These results suggest that spinal SST(2A) receptors play a key role in triggering the generation, but not maintenance, of thermal hyperalgesia evoked by CFA-induced inflammation. The up-regulation of SST(2A) receptors in the spinal cord may be one of the mechanisms underlying inflammation-induced thermal hyperalgesia.
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Neurochemical research · Jul 2008
Randomized Controlled Trial Comparative StudyPlasma concentrations of brain-derived neurotrophic factor in patients undergoing minor surgery: a randomized controlled trial.
We measured perioperative plasma concentrations of brain-derived neurotrophic factor (BDNF), a major mediator of synaptic plasticity in the central nervous system, in males, 30-65 years old, undergoing lumbar or cervical discotomy. Patients were randomly allocated to a general anesthetic with propofol induction and maintenance or with thiopental induction and isoflurane maintenance. BDNF plasma concentrations were measured before induction (baseline), 15 min after induction but before start of surgery, at skin closure, in the post-anesthetic care unit, and 24 h postoperatively. ⋯ At 24 h, concentrations significantly decreased below baseline in both groups (propofol: 232 +/- 129 pg ml(-1), P = 0.0015; thiopental-isoflurane: 253 +/- 250 pg ml(-1), P = 0.016). In the propofol group, there was a weak but statistically significant positive correlation (R2 = 0.38, P = 0.026) between the duration of surgery and BDNF plasma concentrations at skin closure. These data suggest that in males undergoing elective minor surgery, BDNF plasma concentrations show a specific pattern that is influenced by the anesthetic technique and, possibly, by the duration of surgery.
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Neurochemical research · May 2008
Ciliary neurotrophic factor-treated astrocyte conditioned medium regulates the L-type calcium channel activity in rat cortical neurons.
Astrocytes are activated by ciliary neurotrophic factor (CNTF) in vivo and in vitro, however, the consequences on the L-type calcium channel (LCC) of neurons are still poorly understood. Therefore, in the present study, whole-cell patch clamp, western-blot and RT-PCR assay were performed to evaluate the effects of CNTF-treated astrocyte conditioned medium (CNTF-ACM) on LCC current (I(Ca)-L) and the expression of Cav1.2 and Cav1.3 in Sprague-Dawley rat cortical neurons. ⋯ We also found an increase in the concentration of fibroblast growth factor-2 (FGF-2) in CNTF-ACM by ELISA assay. Taken together, these findings indicate that CNTF induces the release of factors, including FGF-2, from astrocytes, thereby potentiating the activity of LCC in cortical neurons.
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Neurochemical research · Jan 2008
The expression of NMDA receptor subunits in cerebral cortex and hippocampus is differentially increased by administration of endobain E, a Na+, K+-ATPase inhibitor.
Previous studies showed that endobain E, an endogenous Na+, K+-ATPase inhibitor, decreases dizocilpine binding to NMDA receptor in isolated membranes. The effect of endobain E on expression of NMDA receptor subunits in membranes of rat cerebral cortex and hippocampus was analyzed by Western blot. Two days after administration of 10 mul endobain E (1 microl = 29 mg fresh tissue) NR1 subunit expression enhanced 5-fold and 2.5-fold in cerebral cortex and hippocampus, respectively. ⋯ NR2C subunit expression was unaffected in either area. NR2D subunit enhanced 1.6 and 2.1-fold for cerebral cortex and hippocampus, respectively. Results indicate that endogenous Na+, K+-ATPase inhibitor endobain E differentially modifies the expression of NMDA receptor subunits.
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Neurochemical research · Oct 2007
ReviewLRRK2 low-penetrance mutations (Gly2019Ser) and risk alleles (Gly2385Arg)-linking familial and sporadic Parkinson's disease.
The identification of mutations in the leucine-rich repeat kinase 2 (LRRK2) gene as a cause of autosomal dominant Parkinson's disease (PD) was a major step forward in the genetic dissection of this disorder. However, what makes LRRK2 unique among the known PD-causing genes is that a low-penetrance mutation, Gly2019Ser, is a frequent determinant not only of familial, but also of sporadic PD in several populations from South Europe, North Africa and Middle East. ⋯ Currently, the Gly2019Ser and Gly2385Arg variants represent the most relevant PD-causing mutation and risk allele, respectively, linking the etiology of the familial and the sporadic forms of this disease. Understanding how the dysfunction of LRRK2 protein leads to neurodegeneration might provide crucial insights for unraveling the molecular mechanisms of PD and for developing disease-modifying therapies.