P.2.045 - A novel role for tau protein in the mechanisms of brain damage caused by peripheral neuropathy

Abstract

Chronic pain affects approximately 20% of European population and it is now considered a risk factor for different pathologies [1], such as neuropathic pain. Neuropathic pain has been defined by the International Association for the Study of Pain (IASP) as the pain evoked by a lesion or disease of the somatosensory system and is frequently associated with depression and cognitive impairment [1]. However, the underlying cellular mechanisms through which neuropathic pain triggers these behavioural deficits remain unclear. Accumulating evidence suggests the cytoskeletal protein Tau as a key regulator of neuronal plasticity and pathology as Tau hyperphosphorylation and malfunction are involved in several brain pathologies, such as Alzheimer’s disease (AD) [2], excitotoxicity and chronic stress [3], since experimental studies demonstrate that Tau reduction strategies can block both neuronal and behavioural deficits in the above disease conditions [2,3]. Moreover, our previous work suggests Tau involvement in pain mechanisms and circuitry [4]. Based on the above, the present study monitors the potential role of Tau in the establishment of brain structural and behavioural alterations caused by peripheral neuropathy. We have used right spared nerve injury (SNI) model of peripheral neuropathy in animals lacking Tau protein (Tau knockout (Tau-KO)) and their wildtype (WT) littermates. Establishment of the model and pain intensity were monitored using Von Frey test. A battery of behavioural tests was performed at 6 and 12 weeks after SNI surgery to assess locomotion, anxious and depressive-like behaviour as well as cognitive performance. Two-way ANOVA statistical analysis showed no effect of SNI on locomotion or anxiety-like behaviour in all groups on Open field test (F(1.29)=0.020, p=0.888 and F(1.29)=3.29x10-5, p=0.996, respectively). However, SNI caused a depressive-like behaviour in WT, but not Tau-KO, animals as assessed by Forced swimming (F(1.29)=35.04, p Based on the above behavioural and molecular data, this work provides novel evidence regarding Tau’s role on the establishment of depressive behaviour and cognitive deficits triggered by peripheral neuropathy. These results are in line with previous animal studies that show an essential mediation of Tau protein in brain damage in AD as well as chronic stress conditions [2,3] suggesting role for Tau in pathological conditions beyond AD. Furthermore, these studies add to our limited understanding on molecular precipitators of brain deficits caused by chronic pain offering potential therapeutic targets.