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Roles of Glutamate Transporter and Receptors, Poly (ADPribose) Polymerase, and Transforming Growth Factor-ß1 in Pontosubicular Neuron Necrosis

Department of Mental Retardation and Birth Defect Research, National Institute of Neuroscience, Department of Laboratory Medicine, National Center Hospital for Mental, Nervous, and Muscular Disorders, National Center of Neurology and Psychiatry Tokyo, Japan, Department of Pediatrics, the Second Clinical Hospital, China Medical University, eng), Shenyang, China

Masayuki Itoh, MD

Department of Mental Retardation and Birth Defect Research, National Institute of Neuroscience

Toshimasa Obonai, MD

Department of Mental Retardation and Birth Defect Research, National Institute of Neuroscience, takasima{at}ncnp.go.jp

Sachio Takashima, MD

Department of Mental Retardation and Birth Defect Research, National Institute of Neuroscience, Department of Laboratory Medicine, National Center Hospital for Mental, Nervous, and Muscular Disorders, National Center of Neurology and Psychiatry Tokyo, Japan

The expression of neuron-type glutamate transporters (EAAC-1), AMPA glutamate receptor subunits (GluR1 and GluR2/3), polyadenosine (5'diphosphate-ribose) polymerase (PARP), and transforming growth factor-ß1 was investigated in 20 cases of neonatal pontosubicular neuron necrosis and 12 gestational-age matched controls. Developmental immunoreactivities of EAAC-1, GluR1, and GluR2/3 appeared in the neurons of the pontine nuclei at 29 to 30 weeks' gestation in controls, and then gradually increased with age. However, these activities were decreased in the pontine nucleus of patients with pontosubicular neuron necrosis. Decreases in these immunoreactivities might indicate early degeneration of neurons. Although PARP and transforming growth factor-ß1 immunoreactivity was insignificant or very weak in the pontine nuclei at any age in controls, PARP was markedly expressed in karyorrhectic neurons of the pontine nucleus in patients with pontosubicular neuron necrosis. Transforming growth factor-ß1 immunoreactivity was observed in nonkaryorrhectic neurons of the pontine nuclei. PARP could contribute to the pathogenesis of pontosubicular neuron necrosis more than EAAC-1 or GluR1 or GluR2/3. Transforming growth factor-ß1 could play a role in the protection and repair of damaged neurons. (J Child Neurol 2000;15:362-369).

Journal of Child Neurology, Vol. 15, No. 6, 362-369 (2000)
DOI: 10.1177/088307380001500602


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