RESUMO
Hippocampal cytoarchitectural abnormalities may be part of the cerebral substrate of schizophrenia. Amongst the chemical components being abnormal in brains of schizophrenics are altered calcium concentrations and reduced expression of the neurotrophin receptor, trkB. We studied by immunohistochemical methods the distribution of visinin-like protein-1 (VILIP-1), which is a calcium sensor protein and at the same time a trkB mRNA binding protein, in hippocampi of nine schizophrenic patients and nine matched control subjects. In normal hippocampi VILIP-1 immunoreactivity was found in multiple pyramidal cells and interneurons. A portion of VILIP-1 immunoreactive interneurons co-express calretinin (60%) and parvalbumin (<10%). In schizophrenics fewer pyramidal cells but more interneurons were immunostained. Our data point to an involvement of the protein in the altered hippocampal circuitry in schizophrenia.
Assuntos
Proteínas de Ligação ao Cálcio/biossíntese , Hipocampo/metabolismo , Proteínas do Tecido Nervoso/biossíntese , Receptores de Detecção de Cálcio , Esquizofrenia/metabolismo , Análise de Variância , Proteínas de Ligação ao Cálcio/análise , Feminino , Hipocampo/química , Humanos , Interneurônios/química , Interneurônios/metabolismo , Masculino , Pessoa de Meia-Idade , Proteínas do Tecido Nervoso/análise , Neurocalcina , Células Piramidais/química , Células Piramidais/metabolismoRESUMO
OBJECTIVES: Abnormalities of brain white matter and oligodendroglia are replicated findings in schizophrenia research. The largely oligodendroglia-associated enzyme ADAM (A disintegrin and metalloprotease) 12 might be involved in the patho-physiology of schizophrenia, because the gene coding for human ADAM12 is located on chromosome 10q26.3, a gene locus which has been linked to schizophrenia, and some of its putative substrates are altered in schizophrenia. METHODS: We studied the numerical density of ADAM12 expressing oligodendrocytes in post-mortem prefrontal brains of patients with haloperidol treated, chronic schizophrenia and matched controls. RESULTS: A significantly reduced numerical density of ADAM12 immunoreactive oligodendrocytes was found in the white matter of the anterior cingulate cortex of schizophrenic patients. CONCLUSIONS: Although the pathophysiological implications of this finding are currently unknown, it is well conveyable that reduced ADAM12 protein contributes to a deviant metabolism of some of its substrates. These substrates are either parts of important signalling cascades (EGF, betacellulin, TGF-beta) or chemical components of myelin (neurofascin-ankyrin) known to be compromised in schizophrenia.
Assuntos
Proteínas ADAM/genética , Giro do Cíngulo/patologia , Proteínas de Membrana/genética , Oligodendroglia/patologia , Esquizofrenia/genética , Esquizofrenia/patologia , Proteínas ADAM/análise , Proteína ADAM12 , Western Blotting , Cromossomos Humanos Par 10/genética , Feminino , Regulação Enzimológica da Expressão Gênica/genética , Humanos , Masculino , Proteínas de Membrana/análise , Pessoa de Meia-Idade , Córtex Pré-Frontal/patologia , Valores de Referência , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transdução de Sinais/genéticaRESUMO
Catechol-O-methyltransferase (COMT) plays an important role in brain catecholamine metabolism. Several studies point to the involvement of COMT in schizophrenia. We applied COMT immunohistochemistry to paraffin-embedded brain sections and assessed the cell density of COMT expressing glial cells and COMT expressing neurons in the gray matter of the frontal cortex of patients with schizophrenia compared with control subjects. We found a significantly increased cell density of COMT expressing glial cells (p=0.003), but an unchanged cell density of COMT expressing neurons (p=0.778) in the gray matter of the frontal cortex of patients with schizophrenia compared with control subjects. Our study demonstrates that schizophrenia might involve increased COMT expression in glial cells in the frontal cortex, which might be associated with a neuronal-glial abnormality and a disturbed dopamine-glutamate interaction.
Assuntos
Catecol O-Metiltransferase/metabolismo , Dopamina/metabolismo , Lobo Frontal/enzimologia , Ácido Glutâmico/metabolismo , Esquizofrenia/metabolismo , Bancos de Espécimes Biológicos , Comunicação Celular , Feminino , Lobo Frontal/patologia , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Neuroglia/enzimologia , Neuroglia/patologia , Neurônios/enzimologia , Neurônios/patologia , Inclusão em Parafina , Esquizofrenia/patologia , Fatores de TempoRESUMO
ADAM12 is a member of the large family of multidomain metalloprotease-disintegrins which possess cell-binding and metalloprotease properties. Typically, ADAM12 is expressed in mesenchymal cells, developing and regenerating heart and skeletal muscle, bone as well as in certain tumours. This report shows by means of reverse transcriptase-polymerase chain reaction (RT-PCR) and immunohistochemistry that the protease ADAM12 is detectable in human and rat brain tissue as well as in cultured cells derived from rat brain. With the exception of a very few immunopositive pyramidal neurons in the developing rat brain, the cellular localization of ADAM12 was exclusively confined to oligodendroglial cells. Thus, ADAM12 may be regarded a new suitable marker for this cell type.