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Lack of neuroprotective effect of astroglia-derived BDNF on hippocampal cell cultures exposed to trimethyltin

100%

Figiel L., Wlodarczyk J.

Acta Neurobiologiae Experimentalis

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2009

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tom 69

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nr 3

It is well known that in response to neuronal injury activated glial cells produce pro-infl ammatory cytokines and neurotrophic factors. These immunoregulatory molecules may play either neurotoxic or neuroprotective roles. In previous studies on mixed neuronal-glial cultures of rat hippocampal dentate gyrus we demonstrated that trimethyltin (TMT) induced neuronal cell death accompanied by an enhanced production of tumor necrosis factor alpha (TNF-α) in microglial cells and a strong increase in TNF-α receptor 1 (TNFR1) expression on astrocytes. Since evidence has been provided that TNFR1 could mediate the production of neurotrophic factors, in the current studies we examined whether the brain-derived neurotrophic factor (BDNF) is up-regulated after TMT exposure and whether it may exert neuroprotective effect on dentate granule cells. Using western blot analysis and immunocytochemical staining we have shown a dose-dependent increase in BDNF production, mainly in astrocytes. Quantitative fl uorescence analysis revealed that addition of anti-TNFR1 antibody to TMTtreated cultures suppresses the astroglial synthesis of BDNF. Nevertheless, immunocytochemical studies of active caspase-3 demonstrated the high level of its expression in cultures exposed to TMT, as well as in cultures pre-treated with BDNF. Our data suggest the involvement of TNFR1 pathway in BDNF production in astrocytes and indicate that this neurotrophic factor does not protect granule neurons against TMT injury.

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Dystroglycan influences the morphology and function of hippocampal neurons in vitro

80%

Figiel L., Bijata M., Wlodarczyk J., Kaczmarek L.

Acta Neurobiologiae Experimentalis

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2013

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tom 73

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nr Suppl.1

Dystroglycan (DG) is a cell adhesion receptor composed of αand β-subunits that form a transmembrane link between the extracellular matrix and the intracellular actin cytoskeleton. Loss of DG function is implicated in muscular dystrophies and the aetiology of epithelial cancers. We have previously reported that β-DG is a target for matrix metalloproteinase-9 (MMP-9), an extracellularly operating enzyme, known to be pivotal for synaptic plasticity, learning and memory. This may suggest an important role of β-DG cleavage by MMP-9 in neuronal activity. Although it has been demonstrated that deletion of DG in neurons blunted hippocampal long-term potentiation (LTP), detailed knowledge concerning mechanisms of action of DG in neuronal cells is still lacking. To study the role of DG in neuronal structure and function we used the lentiviral vector (LV) to deliver shRNA, specifically silencing DG in cultured hippocampal neurons. We found that knockdown of DG simplifies dendritic arbor morphology as well as decreases the total length of dendrites. To determine whether DG deletion influences the dendritic spine shape and motility we performed life imaging of MMP-9-treated cultures. We observed differences in spine remodeling between control and LV-infected neurons. Our results suggest that DG is required for proper neuronal maturation and dendritic spine plasticity.

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Cooperative involvement of serotonergic signalling and MMP-9 in synaptic plasticity

71%

Bijata M., Figiel L., Ponimaskin E., Kaczmarek L., Wlodarczyk J.

Acta Neurobiologiae Experimentalis

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2013

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tom 73

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nr Suppl.1

The brain plasticity is a re-organization of the neuronal and synaptic networks that allows for changes in response to incoming environmental stimuli. Pathological forms of neuronal plasticity underlie the multiple neuropsychiatric disorders like depression. Clinical observations on the efficacy of antidepressants targeting serotonergic system strongly suggest that serotonin and its receptors play a pivotal role in modulation of pathological plasticity. It is known that matrix metalloproteinase-9 is one of the most important biomarker in depression and polymorphism in this protein affect bipolar disorder. We have recently shown that MMP-9, having an established role in synaptic plasticity, influences dendritic morphology in a similar way to that obtained after the 5-HT7 receptor stimulation, e.g. it induces formation of long, thin dendritic spines. It is also known that stimulation of 5-HT7 receptor leads to activation of small Rho GTPase – Cdc42 in fibroblast cell line and in neurons. In this work we investigate whether MMP-9 substrate represents a novel downstream effector of 5-HT7 receptor. Our results indicate that stimulation of the 5-HT7 receptor increases MMP-9 activity toward its synaptic substrates and results in activation of small Rho GTPases.

Ograniczanie wyników

3 Acta Neurobiologiae Experimentalis

3 Figiel L.

3 Wlodarczyk J.

2 Bijata M.

2 Kaczmarek L.

1 Ponimaskin E.

2 2013

1 2009

Lack of neuroprotective effect of astroglia-derived BDNF on hippocampal cell cultures exposed to trimethyltin

Dystroglycan influences the morphology and function of hippocampal neurons in vitro

Cooperative involvement of serotonergic signalling and MMP-9 in synaptic plasticity