Biomedical subjects

Cristina Cid

Publications and source records attributed to Cristina Cid.

4 recordsLinked to original sources

PubMed2005

Anti-heat shock protein 90beta antibodies decrease pre-oligodendrocyte population in perinatal and adult cell cultures. Implications for remyelination in multiple sclerosis.

Lesions in the CNS of patients with multiple sclerosis (MS) often fail to remyelinate, resulting in neurological dysfunction. A key factor seems to be the inefficiency of oligodendrocyte precursor cells (OPCs). We recently reported antibodies against heat shock protein 90beta (Hsp90beta) in MS patients that recognized the antigen on the OPC surface. This study investigates the mechanism and result of anti-Hsp90beta antibody attack. These antibodies induced OPC death in culture in a complement-dependent fashion. Anti-Hsp90beta antibody-induced, complement-mediated OPC death only operated in these cells and caused a significant reduction in the number of O4-positive pro-oligodendrocytes (pre-oligodendrocytes). Adult cultured OPCs also expressed Hsp90beta on their cell surface and were attacked by anti-Hsp90beta antibodies leading to a significant decrease in the pre-oligodendrocyte population. In the presence of low levels of anti-Hsp90beta antibody--i.e. in the range seen in the CSF of MS patients--the complement concentration was critical to reduce the pre-oligodendrocyte population (via attack to OPCs). Higher concentrations of anti-Hsp90beta antibodies and complement became extinct the pre-oligodendrocytes. Complement 1-esterase inhibitor prevented these effects in the pre-oligodendrocyte population. These findings demonstrate, for the first time in vitro, a feasible mechanism to decrease the production of new oligodendrocytes, thus limiting the possibility of remyelination.

Adult↗

PubMed2003

Antibodies reactive to heat shock protein 90 induce oligodendrocyte precursor cell death in culture. Implications for demyelination in multiple sclerosis.

Oligodendrocyte precursor cells (OPCs) are extremely efficient at remyelination. These cells persist in the adult human central nervous system and can proliferate. However, the failure to remyelinate is a pathological characteristic of the human demyelinating disease multiple sclerosis (MS), which suggests that these cells are ineffective in this disorder. This paper reports that IgG antibodies in the cerebrospinal fluid (CSF) of MS patients specifically recognize an antigen on OPCs in culture. Control patients were found not to possess these antibodies. The antigen was immunoprecipitated in cell extracts from cultures with purified IgG from MS CSF. Peptide mass fingerprinting identified it as the beta type of heat shock protein 90 (Hsp90). Two-dimensional electrophoresis and immunoblot showed that this antigen in fact corresponds to two specific isoforms of Hsp90beta. Several control assays using monoclonal and polyclonal anti-Hsp90 antibodies confirmed the specific expression of Hsp90 on OPCs. Labeling OPCs in vivo with MS CSF and anti-Hsp90 antibodies and subsequent immunofluorescence confocal microscopy located the antigen on the cell surface. The binding of CSF antibodies from MS patients to the OPC surface led to complement activation and significant extinction of the OPC population. These results suggest that OPCs may be a target of anti-Hsp90 antibodies in MS patients and that this could prevent remyelination.

Antibodies↗

PubMed2003

Low concentrations of glutamate induce apoptosis in cultured neurons: implications for amyotrophic lateral sclerosis.

Evidence is accumulating that excessive glutamate concentration in the extracellular space is neurotoxic and plays a role in amyotrophic lateral sclerosis (ALS). However, the published results on glutamate levels in cerebrospinal fluid (CSF) and on glutamate-mediated toxicity of CSF in ALS disease remain controversial. In this report, we studied CSF from patients with sporadic ALS and controls to determine glutamate concentrations, and then analyzed the neurotoxic effect of glutamate at the concentrations present in CSF from ALS patients on cultured cortical neuronal cells. Our study shows that glutamate, at the concentrations found in CSF from ALS patients (5.8 microM), diminished cell viability and increased apoptosis determined by the fluorescent DNA-binding dye Hoechst 33342 as well as by Terminal deoxynucleotidyl transferase (TdT)-mediated dUTP Nick End-Labeling (TUNEL) reaction in cultured neuronal cells. However, glutamate concentrations as those found in CSF from controls (2.8 microM or below) did not induce any effect. Both significant glutamate-induced effects were inhibited in the presence of NBQX (2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo(f)quinoxaline-2,3-dione), an alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA)/kainate-sensitive glutamate receptor antagonist. These results demonstrate that AMPA/kainate receptors are involved in the glutamate-mediated neurotoxic effects on cultured neurons, according to reports that implicate these receptors in ALS disease. We conclude that the glutamate-mediated neuronal apoptosis through AMPA/kainate receptors could occur in ALS patients who have elevated CSF glutamate concentration.

Aged↗

PubMed2002

Neuronal apoptosis induced by cerebrospinal fluid from multiple sclerosis patients correlates with hypointense lesions on T1 magnetic resonance imaging.

Neuronal damage seems to be a major source of disability in multiple sclerosis (MS) patients and at present magnetic resonance imaging (MRI) is a sensitive method to evaluate lesion and disease activity. We studied the potential correlation between changes in MS patients' disability after relapse, the degree of T1 lesion hypointensity on MRI in vivo and neuronal apoptosis induced by cerebrospinal fluid (CSF) on neuron cultures. In this study, we included 24 MS patients with relapsing disease. Clinical recovery from relapse was measured by the Expanded Disability Status Scale (EDSS). T1-weighted MRI studies were done according to established standards and neuronal apoptosis was induced by treatment of neuronal cultures with CSF from patients while relapsing. Recovery after relapse is inversely correlated with neuronal apoptosis (r=-0.725, p<0.0001). A correlation was found between T1 lesion hypointensity and a poor recovery from relapse (r=0.656, p=0.0005) and such hypointensity correlated strongly with neuronal apoptosis (r=-0.779, p<0.0001). CSF from all patients with hypointense T1 lesions caused significantly increased neuronal apoptosis, whereas all CSF that did not induced such effects corresponded to patients without T1 lesions. The recovery from an acute MS relapse is significantly worse in patients with hypointense T1 lesions in MRI and in those whose CSF damaged neurons on cultures in vitro, phenomena that closely correlated each other.

Adolescent↗