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Author Notes:

Machelle T. Pardue, Atlanta VA Center of Excellence in Visual and Neurocognitive Rehabilitation, Research Service (151 Oph), 1670 Clairmont Rd., Decatur, GA 30033, Telephone: (404)321-6111 X17342, Fax: (404)728-4847, machelle.pardue@bme.gatech.edu.

All authors contributed substantiatively to this manuscript, including designing the study (Allen, Hanif, Gogniat, Prall, Boatright, Pardue); running the experiments and collecting the data (Allen, Hanif, Gogniat, Prall, Haider, Aung, Prunty, Mees, Coulter); analyzing the data and interpreting the results (Allen, Hanif, Gogniat, Prall, Haider, Aung, Prunty, Mees, Coulter, Motz, Boatright, Pardue); writing the manuscript and crafting the figures (Allen, Hanif, Gogniat, Haider, Coulter, Motz, Pardue); and reading and editing the paper (all authors).

None of the authors have any interest or relationship, financial or otherwise, which might be perceived as influencing the objectivity of the author.

Subjects:

Research Funding:

This work was supported by the National Institutes of Health [grant numbers P30 EY006360, R01 EY014026, and T32 EY007092-27 ]; the Rehabilitation R&D Service of the Department of Veterans Affairs (Merit Award I01RX000951; and Research Career Scientist Award to MTP); Research to Prevent Blindness; and the Abraham J. and Phyllis Katz Foundation.

Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Neurosciences
  • Neurosciences & Neurology
  • diabetes
  • diabetic retinopathy
  • exercise
  • neurotrophin-4
  • TrkB
  • DOPAMINERGIC AMACRINE CELLS
  • NEUROTROPHIC FACTOR
  • COGNITIVE FUNCTION
  • AEROBIC EXERCISE
  • PHYSICAL-ACTIVITY
  • GANGLION-CELLS
  • HIPPOCAMPAL NEUROGENESIS
  • MICROVASCULAR DISEASE
  • AXON REGENERATION
  • IMPROVES MEMORY

TrkB signalling pathway mediates the protective effects of exercise in the diabetic rat retina

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Journal Title:

European Journal of Neuroscience

Volume:

Volume 47, Number 10

Publisher:

, Pages 1254-1265

Type of Work:

Article | Post-print: After Peer Review

Abstract:

Diabetic retinopathy is a leading cause of vision loss. Treatment options for early retinopathy are sparse. Exercise protects dying photoreceptors in models of retinal degeneration, thereby preserving vision. We tested the protective effects of exercise on retinal and cognitive deficits in a type 1 diabetes model and determined whether the TrkB pathway mediates this effect. Hyperglycaemia was induced in Long Evans rats via streptozotocin injection (STZ; 100 mg/kg). Following confirmed hyperglycaemia, both control and diabetic rats underwent treadmill exercise for 30 min, 5 days/week at 0 m/min (inactive groups) or 15 m/min (active groups) for 8 weeks. A TrkB receptor antagonist (ANA-12), or vehicle, was injected 2.5 h before exercise training. We measured spatial frequency and contrast sensitivity using optokinetic tracking biweekly post-STZ; retinal function using electroretinography at 4 and 8 weeks; and cognitive function and exploratory behaviour using Y-maze at 8 weeks. Retinal neurotrophin-4 was measured using ELISA. Compared with non-diabetic controls, diabetic rats showed significantly reduced spatial frequency and contrast sensitivity, delayed electroretinogram oscillatory potential and flicker implicit times and reduced cognitive function and exploratory behaviour. Exercise interventions significantly delayed the appearance of all deficits, except for exploratory behaviour. Treatment with ANA-12 significantly reduced this protection, suggesting a TrkB-mediated mechanism. Despite this, no changes in retinal neurotrohin-4 were observed with diabetes or exercise. Exercise protected against early visual and cognitive dysfunction in diabetic rats, suggesting that exercise interventions started after hyperglycaemia diagnosis may be a beneficial treatment. The translational potential is high, given that exercise treatment is non-invasive, patient controlled and inexpensive.

Copyright information:

© 2018 Federation of European Neuroscience Societies and John Wiley & Sons Ltd

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