engleski

Activity dependent regulation of neurocan in the hippocampus

Extracellular matrix molecules are involved in important cell functions such as proliferation, migration, morphological differentiation and synaptic plasticity. A candidate molecule that could be involved in the regulation of physiological and pathological neuronal activity is the chondroitin sulphate proteoglycan neurocan. In order to test whether neuronal activity can regulate neurocan expression in the adult brain, we have used a well established animal model of hippocampal excitotoxicity (Sloviter RS, 1987, Science 235:73-76). In this model, 24h high frequency stimulation of the perforant path, the main afferent input to the hippocampus, was performed in adult rats. In situ hybridization revealed upregulation of neurocan mRNA in astrocytes within the ipsi- and contralateral hippocampus 0-1 days after 24 hours of high frequency stimulation. mRNA upregulation was confirmed by laser-microdissection of selected hippocampal regions and subsequent quantitative RT-PCR. Neurocan-immunoreactivity exhibited a more defined localization to the dentate gyrus with strongest immunostaining in the hilar area and ipsilateral outer molecular layer. The expression of neurocan was dependent on the intensity and duration of perforant path stimulation. Under conditions of low frequency paired pulse stimulation neurocan mRNA upregulation and immunoreactivity was restricted to the ipsilateral outer molecular layer, i.e. the termination site of the stimulated afferent fibers. Our results demonstrate that neurocan is strongly expressed in the dentate gyrus of adult rats following high frequency stimulation of the perforant path as well as under conditions of forced afferent stimulation. This suggests an activity-dependent regulation of neurocan in the adult nervous system.

hippocampus; plasticity; neurocan

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