engleski

The role of neuroplastin cell adhesion molecule in postnatal development and degeneration of the hippocampal trisynaptic circuit

The hippocampal trisynaptic pathway is a key neuronal circuit underlying processes of learning and memory. It is known that diverse family of cell adhesion molecules (CAMs) is involved in complex regulation of neural development and plasticity. Additionally, published data show upregulation of CAMs in different neurodegenerative processes. CAM neuroplastin 65 (Np65), a brain-specific isoform of this transmembrane glycoprotein, has been implicated in learning and memory. Previous studies revealed that antibodies against Np65 inhibit maintenance of LTP, and genetically induced deletion of Np65 causes retrograde amnesia in mice. We aimed to describe development of the Np65 immunoreactivity pattern in formalin-fixed paraffin-embedded (FFPE) human hippocampal tissue from 14th gw to adulthood, as well as in neurodegeneration, and to verify the period in which Np appears in the hippocampal sublayers whose neurons are specific relay stations of the trisynaptic pathway. FFPE hippocampal human fetal tissue and hippocampal sections from middle childhood and adulthood, as well as hippocampal tissue affected by sporadic Alzheimer’s disease (AD) were analyzed. We report that the presence of neuroplastin in the hippocampus similar to postnatal and adult pattern appears gradually around birth term. We found the Np immunoreactivity intensity to increase in the early phase of AD and decrease in Np total immunoreactivity in the late stages of AD. We conclude that increasing Np65 expression coincides with formation of synapses and propose it is one of the key molecules necessary for proper functioning of the trisynaptic pathway and propose it as one of the key molecules necessary for proper functioning of this information pathway in the hippocampus. Np upregulation in early AD could suggest possible plastic compensatory mechanism to neurodegenerative injury, while the loss could be associated with degeneration of trysinaptic pathway that underlies severe memory impairment in AD.

neuroplastin ; cell adhesion molecules ; hippocampus ; neurodevelopment ; Alzheimer's disease

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