Interleukin-1 beta down-regulates the expression of metabotropic glutamate receptor 5 in cultured human astrocytes.

Expression of metabotropic glutamate receptor 5 (mGluR5) protein is known to be plastic and to depend critically on the astrocytes' microenvironment. In the present study we investigated whether interleukins, which are involved in the immune response following brain injury, could contribute to the regulation of mGluR5 protein in human astrocytes in culture. Using Western blotting and immunocytochemistry, no detectable changes in the expression of the mGluR5 protein were observed with both interleukin 1beta and interleukin 6 in undifferentiated cultures (growing in serum free media).

Activation of metabotropic glutamate receptor 3 enhances interleukin (IL)-1beta-stimulated release of IL-6 in cultured human astrocytes.

Previous studies have demonstrated that human astrocytes express mRNA and receptor protein for group I and II metabotropic glutamate receptors (mGluRs). Whether these receptors can influence the inflammatory and immune response and can modulate the capacity of astrocytes to produce inflammatory cytokines is still unclear. Inflammatory cytokines can be produced by activated glial cells and play a critical role in several neurological disorders.

Expression and functional role of mGluR3 and mGluR5 in human astrocytes and glioma cells: opposite regulation of glutamate transporter proteins.

We examined the regulation of glutamate transporter protein expression after stimulation with selective metabotropic glutamate receptor (mGluR) agonists in cultured human glial cells. mGluR3 and mGluR5 are expressed in human astrocytes and in human glioma cells in vivo as well as in vitro, as shown by either RT-PCR or western blot analysis. The selective group I agonist (S)-3,5-dihydroxyphenylglycine produced a significant down-regulation of both GLAST and GLT-1 protein expression in astrocytes cultured in the presence of growth factors.

Expression and regulation of voltage-gated sodium channel beta1 subunit protein in human gliosis-associated pathologies.

Auxiliary beta1 subunits of voltage-gated sodium channels (NaChs) critically regulate channel activity and may also act as cell adhesion molecules (CAMs). In a recent study we have shown that the expression of beta1 NaCh protein is increased in reactive astrocytes in a rat epilepsy model of mesial temporal lobe epilepsy. The present study was undertaken to examine whether changes of NaCh beta1 subunit protein expression are also associated with structural changes occurring in human reactive astrocytes under different pathological conditions in vivo, as well as in response to changing environmental conditions in vitro.

Immunohistochemical localization of group I and II metabotropic glutamate receptors in control and amyotrophic lateral sclerosis human spinal cord: upregulation in reactive astrocytes.

Excitotoxicity, which is mediated by the excessive activation of glutamate receptors, has been implicated in the pathogenesis of amyotrophic lateral sclerosis (ALS). There is substantial information about the distribution and function of ionotropic glutamate receptors in the spinal cord, although the role of metabotropic glutamate receptors (mGluRs) is poorly understood in this region of the brain, particularly under pathological conditions. We used immunocytochemistry to study the general distribution of group I and group II mGluR immunoreactivity in the human spinal cord, as well as the cell-specific expression of these receptors.

Ionotropic and metabotropic glutamate receptor protein expression in glioneuronal tumours from patients with intractable epilepsy.

Glioneuronal tumours are an increasingly recognized cause of chronic pharmaco-resistant epilepsy. In the present study the immunocytochemical expression of various glutamate receptor (GluR) subtypes was investigated in 41 gangliogliomas (GG) and 16 dysembryoplastic neuroepithelial tumours (DNT) from patients with intractable epilepsy. Immunocytochemistry with antibodies specific for ionotropic NR1, NR2A/B (NMDA) GluR1, GluR2 (AMPA), GluR5-7 (kainate), and metabotropic mGluR1, mGluR2-3, mGluR5, mGluR7a subtypes demonstrated in both GG and DNT the presence of an highly differentiated neuronal population, containing subunits from each receptor class.

Expression of connexin 43 and connexin 32 gap-junction proteins in epilepsy-associated brain tumors and in the perilesional epileptic cortex.

The expression of the gap-junction proteins connexin (CX) 43 and 32 was evaluated in surgical specimens of brain tumors and perilesional cortex from patients with chronic medically intractable epilepsy. In human normal brain CX32 was expressed in neurons and oligodendrocytes. CX32 immunoreactivity (IR) was observed in the neuronal component of glioneuronal tumors and in all oligodendrogliomas, 50% of which showed strong labeling, independent of the grade of differentiation.

Expression of brain-derived neurotrophic factor and tyrosine kinase B receptor proteins in glioneuronal tumors from patients with intractable epilepsy: colocalization with N-methyl-D-aspartic acid receptor.

Recent evidence suggests that brain-derived neurotrophic factor (BDNF) and its tyrosine kinase B (TrkB) receptor, in addition to promoting neuronal survival and differentiation, modulates synaptic transmission by increasing N-methyl-D-aspartic acid receptor (NMDAR) activity. Overexpression of BDNF may, then, interfere with normal brain function, causing increased excitability. We have examined the immunohistochemical expression of BDNF, full-length TrkB receptor and the NMDAR subunit 1 and subunit 2A/B proteins (NMDAR1 and NMDAR2A/B) in glioneuronal tumors (gangliogliomas, GG, n = 40; dysembryoplastic neuroepithelial tumors, DNT, n = 15), from patients with chronic intractable epilepsy.

Increased expression of neuronal nitric oxide synthase spliced variants in reactive astrocytes of amyotrophic lateral sclerosis human spinal cord.

The expression of three different neuronal nitric oxide synthase (nNOS) spliced variants, named nNOSalpha, nNOSbeta, and nNOSgamma, was investigated in the spinal cord of control and both familiar and sporadic amyotrophic lateral sclerosis (FALS and SALS) patients. Western blot analysis showed a consistent increase in nNOS expression in six SALS patients compared with controls when antibodies recognizing both nNOSalpha and nNOSbeta, or nNOSalpha, nNOSbeta, and nNOSgamma were used, whereas no change was observed when a selective anti-nNOSalpha antibody was used. Immunoreactivity signal for nNOSalpha-beta-gamma and nNOSalpha-beta was equally present in ventral horn neurons of control and ALS spinal cord but was dramatically increased in reactive astrocytes of the ventral horn and white matter in both FALS and SALS.

Induction of neonatal sodium channel II and III alpha-isoform mRNAs in neurons and microglia after status epilepticus in the rat hippocampus.

Sodium channels (NaChs) regulate neuronal excitability in both physiological and pathological conditions, including epilepsy and are therefore an important target for antiepileptic drugs. In the present study, we examined the distribution of mRNAs encoding neonatal NaChs II and III alpha-isoforms in control rat hippocampus and after electrically-induced status epilepticus (SE), using nonradioactive in situ hybridization (ISH). Only weak expression of neonatal NaCh II and III mRNAs was observed in control hippocampus.

Glioneuronal tumors and medically intractable epilepsy: a clinical study with long-term follow-up of seizure outcome after surgery.

The present study intends to identify factors that predict postoperative clinical outcome in patients with gangliogliomas (GG) and dysembryoplastic neuroepithelial tumors (DNT). We evaluated the medical records of 45 patients with GG and 13 patients with DNT, treated surgically between 1985 and 1995. We assessed several clinical and histopathological features and analyzed the data statistically.