A118G polymorphism of OPRM1 gene is associated with schizophrenia.

Schizophrenia is ranked among multifactor diseases in whose pathogenesis, besides environmental factors, an interplay of functional polymorphisms of a larger number of candidate genes is involved. Neurodevelopmental abnormities are among the most accepted hypotheses in the etiology of schizophrenia. Recently, the role of oligodendrocytes in the development of the cortex has been cited repeatedly.

Different transfer of nociceptive sensitivity from rats with postnatal hippocampal lesions to control rats.

Hippocampal lesions in newborn rats alter the development of mechanisms involved in the processing of nociception. The hippocampal lesion was induced by the bilateral infusion, into the lateral cerebral ventricles, of 0.25 microL of saline containing either 0.

Neonatal administration of N-acetyl-L-aspartyl-L-glutamate induces early neurodegeneration in hippocampus and alters behaviour in young adult rats.

N-acetyl-L-aspartyl-L-glutamate (NAAG) is a dipeptide that could be considered a sequestered form of L-glutamate. As much as 25% of L-glutamate in brain may be present in the form of NAAG. NAAG is also one of the most abundant neuroactive small molecules in the CNS: it is an agonist at Group II metabotropic glutamate receptors (mGluR II) and, at higher concentrations, at the N-methyl-D-aspartate (NMDA) type of ionotropic glutamate receptors.

Glutamatergic hypothesis of schizophrenia: involvement of Na+/K+-dependent glutamate transport.

Hypothetical model based on deficient glutamatergic neurotransmission caused by hyperactive glutamate transport in astrocytes surrounding excitatory synapses in the prefrontal cortex is examined in relation to the aetiology of schizophrenia. The model is consistent with actions of neuroleptics, such as clozapine, in animal experiments and it is strongly supported by recent findings of increased expression of glutamate transporter GLT in prefrontal cortex of patients with schizophrenia. It is proposed that mechanisms regulating glutamate transport be investigated as potential targets for novel classes of neuroactive compounds with neuroleptic characteristics.

Quinolinic acid induces NMDA receptor-mediated lipid peroxidation in rat brain microvessels.

Quinolinic acid increased the generation of lipid peroxidation products by isolated rat brain microvessels in vitro. The effect was inhibited both by a specific NMDA receptor antagonist D-2-amino-5-phosphonovaleric acid and by reduced glutathione (GSH). Furthermore, quinolinic acid displaced specific binding of [(3)H]-L-glutamate by cerebral microvessel membranes, particularly in the presence of NMDA receptor co-agonist (glycine) and modulator (spermidine).

Main subunits of ionotropic glutamate receptors are expressed in isolated rat brain microvessels.

Excitatory amino acids are known to modulate blood-brain barrier (BBB) permeability, however, the information on glutamate receptors in cerebral capillaries is inconsistent. In the present study, freshly isolated microvessels obtained from saline-perfused rat brains were used. Gene expression of the main N-methyl-D-aspartate (NMDA) and alpha-amino-3-hydroxy-5-methyl-isoxazole-4-propionic acid (AMPA) receptor subunits NMDAR1 and GLUR1, respectively, were investigated by reverse transcription-polymerase chain reaction (RT-PCR).

N-Acetyl-L-aspartyl-L-glutamate changes functional and structural properties of rat blood-brain barrier.

Intracerebroventricular administration of N-acetyl-L-aspartyl-L-glutamate (NAAG), an agonist at group II metabotropic and NR1/NR2D-containing N-methyl-D-aspartate (NMDA) ionotropic glutamate receptors, increased the permeability of the blood-brain barrier (BBB) to serum albumin in the striatum, but produced no similar effects in the entorhinal cortex or in the hippocampal formation. Electron microscopy showed that NAAG, but not its hydrolytic products L-glutamate and N-acetyl-L-aspartate, increased the number of transport vesicles in the hippocampal endothelial cells. Furthermore, immunocytochemistry detected NR2D subunits on hippocampal capillaries.