Chronic Mild Therapeutic Hypothermia modulate Irisin, BDNF and cognitive functions in an AD-like rat model.

BEATRIZ BISTUE; C. FABIAN LOIDL; A. CLAUDIO CUELLO; MARTIN A. BRUNO

Denver

Congreso; Alzheimer's Association International Conference 2021; 2021

Background: Hypothermia induces the release of adipomiokines implicated in neuroprotection, although the underlyingmechanisms are not fully understood1–3. Irisin is released by muscle tissue upon physical activity and has been shown toregulate metabolism in different tissues. Interestingly, previous reports demonstrated that cold exposure increased irisinproportional to shivering intensity, in magnitude similar to exercise-secretion4. Irisin attracted interest due to its beneficialprotective actions in AD models. Researchers found less irisin in the CSF of people with MCI and AD than in controls,whereas irisin ran higher among older people with normal cognition. Exercise-linked irisin exerted protective actions in ADmodels, rescuing synaptic plasticity and memory defects5,6. BDNF has been known to play a critical role in synapticfunction, learning, memory and neuronal survival7. Interestingly, irisin is the upstream mediator of BDNF production andtriggers its brain expression upon aerobic excercise7, improving memory in persons with intact cognition, MCI ordementia8–10. Rising irisin levels may constitute a novel therapeutic strategy to prevent cognitive decline. Thus, wehypothesized that repeated cold exposures may delay disease progression, representing a potential target for AD. So, wedesigned a non-pharmacological therapeutic strategy applying chronic mild hypothermia to induce neuroprotection andimprove cognitive functions in our transgenic AD-like model.Method: 17 months old transgenic McGill-R-Thy1-APP rats were chronically exposed to a mild hypothermic treatment at4°C 2hs daily during 28 consecutive days. Irisin and BDNF levels were measured by ELISA from plasma andhippocampal homogenates. By Immunohistochemistry, quantification of synaptophysin-immunoreactivity presynapticboutons was compared between controls vs. AD-like treated rats. A hippocampal memory task was performed by Novelobjects Recognition (NOR) test.Result: Our results demonstrated that chronic exposure to a mild hypothermia bolstered Irisin and BDNF hippocampaland plasma levels, increase synaptophysin-positive presynaptic boutons expression and improve cognitive functions.Conclusion: A controlled and repeated mild‐hypothermia constitute a novel non-pharmacological therapeutic strategy tomodulate Irisin levels, prevent neurodegeneration and preserve cognitive functions