Postsynaptic density protein PSD-95 expression in Alzheimer's disease and okadaic acid induced neuritic retraction.
In order to understand how plasticity is related to neurodegeneration, we studied synaptic proteins with quantitative immunohistochemistry in the entorhinal cortex from Alzheimer patients and age-matched controls. We observed a significant decrease in presynaptic synaptophysin and an increase in postsynaptic density protein PSD-95, positively correlated with beta amyloid and phosphorylated Tau proteins in Alzheimer cases. Furthermore, Alzheimer-like neuritic retraction was generated in okadaic acid (OA) treated SH-SY5Y neuroblastoma cells with no decrease in PSD-95 expression. However, in a SH-SY5Y clone with decreased expression of transcription regulator LMO4 (as observed in Alzheimer's disease) and increased neuritic length, PSD-95 expression was enhanced but did not change with OA treatment. Therefore, increased PSD-95 immunoreactivity in the entorhinal cortex might result from compensatory mechanisms, as in the SH-SY5Y clone, whereas increased Alzheimer-like Tau phosphorylation is not related to PSD-95 expression, as suggested by the OA-treated cell models.
Leuba
Geneviève
G
Center for Psychiatric Neuroscience, Department of Psychiatry, CHUV, Lausanne, Switzerland; Service of Old Age Psychiatry, Department of Psychiatry, CHUV, Lausanne, Switzerland.
Walzer
Claude
C
Department of Psychiatry, University Hospital Geneva, Geneva, Switzerland.
Vernay
André
A
Center for Psychiatric Neuroscience, Department of Psychiatry, CHUV, Lausanne, Switzerland; Service of Old Age Psychiatry, Department of Psychiatry, CHUV, Lausanne, Switzerland.
Carnal
Béatrice
B
Center for Psychiatric Neuroscience, Department of Psychiatry, CHUV, Lausanne, Switzerland; Service of Old Age Psychiatry, Department of Psychiatry, CHUV, Lausanne, Switzerland.
Kraftsik
Rudolf
R
Department of Cell Biology and Morphology, Lausanne University, Lausanne, Switzerland.
Piotton
Françoise
F
Department of Psychiatry, University Hospital Geneva, Geneva, Switzerland.
Marin
Pascale
P
Department of Psychiatry, University Hospital Geneva, Geneva, Switzerland.
Bouras
Constantin
C
Department of Psychiatry, University Hospital Geneva, Geneva, Switzerland.
Savioz
Armand
A
Department of Psychiatry, University Hospital Geneva, Geneva, Switzerland. Electronic address: armand.savioz@hcuge.ch.
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D000076122:Disks Large Homolog 4 Protein; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics; D008297:Male; D008565:Membrane Proteins / Q000096:biosynthesis* / Q000235:genetics; D008875:Middle Aged; D016501:Neurites / Q000187:drug effects / Q000473:pathology / Q000502:physiology*; D019319:Okadaic Acid / Q000633:toxicity*; D010766:Phosphorylation; D015854:Up-Regulation / Q000235:genetics; D016875:tau Proteins / Q000378:metabolism
D016229:Amyloid beta-Peptides; C501444:DLG4 protein, human; D000076122:Disks Large Homolog 4 Protein; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D016875:tau Proteins; D019319:Okadaic Acid