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Decreased post-synaptic density-95 protein expression on dendrites of newborn neurons following CX3CR1 modulation in the epileptogenic adult rodent brain

Cellular & Molecular Immunology volume 15, pages 414–417 (2018)Cite this article

Temporal lobe seizures generate a large pool of new hippocampal neurons in the adult brain. Their role within the hyperexcitable neuronal network and how they are regulated by the immune response is unclear. Fractalkine and its receptor CX3CR1 constitute a chemokine pathway known to modulate the immune response in temporal lobe epilepsy. Here, 6 weeks of intracerebroventricular infusion of anti-CX3CR1 antibody, starting 1 week after electrically induced prolonged seizures in the temporal lobe (status epilepticus (SE)), reduced microglial activation within the hippocampus. This was associated with a several-fold decrease in expression of post-synaptic density-95 (PSD-95), a scaffolding protein specific for excitatory synapses on individual retroviral vector-mediated GFP-labeled hippocampal neurons at 6 weeks of age. In contrast, the scaffolding protein at inhibitory synapses, gephyrin, and related adhesion molecules were unaltered. These results indicate that expression of synaptic proteins on adult-born neurons in an epileptogenic environment is sensitive to the inflammatory milieu and may in turn affect excitation/inhibition balance.

Depending on the precipitating injury that precedes epilepsy development, the new neurons may either migrate abnormally into the hilar region of the dentate gyrus and contribute to the pathophysiology of epilepsy or correctly integrate within the granule cell layer (GCL) and have possible dampening effects.1 Previous studies have shown spatial and temporal changes in expression of synaptic proteins, known to regulate the excitatory/inhibitory synaptic balance,2,3 on newborn neurons in animal models of brain inflammation and epileptogenesis.4,5 Modulating the fractalkine-CX3CR1 chemokine pathway has led to reduced cell proliferation and immature neurons in the hippocampus one week after SE.6 In this study, we aimed to evaluate changes in the expression of synaptic scaffolding proteins and adhesion molecules on individual new integrated neurons born and differentiated into the GCL of the hippocampus following temporal SE, with and without immune modulation.

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Acknowledgements

Work supported by Swedish Research Council, ALF Grant, Zoega’s, Tore Nilson’s Foundation, and EU’s Seventh Framework Programme (FP7/2007 2013) (602102). We thank biomedical analysts Susanne Jonsson for technical support.

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Authors and Affiliations

  1. Inflammation and Stem Cell Therapy Group, Division of Clinical Neurophysiology, Lund University, SE-221 84, Lund, Sweden

    Idrish Ali, Una Avdic, Deepti Chugh & Christine T Ekdahl

  2. Lund Epilepsy Center, Lund University, SE-221 85, Lund, Sweden

    Idrish Ali, Una Avdic, Deepti Chugh & Christine T Ekdahl

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  1. Idrish Ali
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Correspondence to Christine T Ekdahl.

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Ali, I., Avdic, U., Chugh, D. et al. Decreased post-synaptic density-95 protein expression on dendrites of newborn neurons following CX3CR1 modulation in the epileptogenic adult rodent brain. Cell Mol Immunol 15, 414–417 (2018). https://doi.org/10.1038/cmi.2017.112

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