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

Abstract

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.