Stress exacerbates neuron loss and microglia proliferation in a rat model of excitotoxic lower motor neuron injury

Denise A. Puga, C. Amy Tovar, Zhen Guan, John C. Gensel, Matthew S. Lyman, Dana M. McTigue, Phillip G. Popovich

Research output: Contribution to journalArticlepeer-review

8 Scopus citations


All individuals experience stress and hormones (e.g., glucocorticoids/GCs) released during stressful events can affect the structure and function of neurons. These effects of stress are best characterized for brain neurons; however, the mechanisms controlling the expression and binding affinity of glucocorticoid receptors in the spinal cord are different than those in the brain. Accordingly, whether stress exerts unique effects on spinal cord neurons, especially in the context of pathology, is unknown. Using a controlled model of focal excitotoxic lower motor neuron injury in rats, we examined the effects of acute or chronic variable stress on spinal cord motor neuron survival and glial activation. New data indicate that stress exacerbates excitotoxic spinal cord motor neuron loss and associated activation of microglia. In contrast, hypertrophy and hyperplasia of astrocytes and NG2+ glia were unaffected or were modestly suppressed by stress. Although excitotoxic lesions cause significant motor neuron loss and stress exacerbates this pathology, overt functional impairment did not develop in the relevant forelimb up to one week post-lesion. These data indicate that stress is a disease-modifying factor capable of altering neuron and glial responses to pathological challenges in the spinal cord.

Original languageEnglish
Pages (from-to)246-254
Number of pages9
JournalBrain, Behavior, and Immunity
StatePublished - Oct 1 2015

Bibliographical note

Funding Information:
This work was supported in part by a Fritz Krauth Memorial Fellow award from the Paralyzed Veterans of America (PVA) (DP), The Ray W. Poppleton Endowment (PGP) and NIH‐NINDS award NS045758. We thank Drs. Michael Beattie and Jacqueline Bresnahan for discussions and input during the initial development of the glutamate injection model.

Publisher Copyright:
© 2015 Elsevier Inc..


  • Glucocorticoid receptor
  • Glucocorticoids
  • Glutamate
  • Hypothalamic-pituitary-adrenal axis
  • Microglia
  • Neuroinflammation
  • Spinal cord injury
  • Stress

ASJC Scopus subject areas

  • Immunology
  • Endocrine and Autonomic Systems
  • Behavioral Neuroscience


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