C10 - Glial leptin signaling in peripheral neuropathy

Peripheral Polyneuropathy is one of the commonest neurological disorders and obesity is its most frequent cause. The underlying pathological mechanisms are elusive and affected patients remain without known cure. Obesity leads to increased levels of leptin, and chronic hyperleptinemia positively correlates with neuropathic symptoms in obese humans, raising the question for a potential causal relationship. Our preliminary data suggest a role for leptin signaling in acute and obesity induced peripheral nerve injury. We here aim to investigate chronic hyperleptinemic mice with regard to neuropathy presentation in lean and otherwise healthy mice, independent of the full-blown clinical picture of obesity. In order to untangle potential neuronal from glial effects of hyperleptinemia on the peripheral nervous system, we will take advantage of conditional mutagenesis by crossbreeding leptin overexpressing mice with mice where the leptin receptor gene is ablated either in Schwann cells or in sensory neurons.