Methamphetamine-associated cognitive decline is attenuated by neutralizing IL-1 signaling

Arkadiusz Liśkiewicz, Marta Przybyła, Minseon Park, Daniela Liśkiewicz, Marta Nowacka-Chmielewska, Andrzej Małecki, Jarosław Barski, Joanna Lewin-Kowalik, Michal Toborek

Research output: Contribution to journalArticle

3 Scopus citations

Abstract

Methamphetamine (METH) abusers are prone to develop a variety of comorbidities, including cognitive disabilities, and the immunological responses have been recognized as an important component involved in the toxicity of this drug. Cytokines are among the key mediators between systemic inflammatory status and tissue responses. One of these, interleukin 1 (IL-1), has been hypothesized to be involved in cognitive functions and also appears to play a pivotal role among inflammatory molecules. In the present study, we demonstrate that exposure of mice to METH markedly increased the protein level of IL-1β in hippocampal tissue. Additionally, METH administration induced a decline in spatial learning as determined by the Morris water maze test. We next evaluated the hypothesis that blocking IL-1β signaling can protect against METH-induced loss of cognitive functioning. The results indicated that METH-induced impaired spatial learning abilities were attenuated by co-administration of mouse IL-1 Trap, a dimeric fusion protein that incorporates the extracellular domains of both of the IL-1 receptor components required for IL-1 signaling (IL-1 receptor type 1 and IL-1 receptor accessory protein), linked to the Fc portion of murine IgG2a. This effect was associated with a decrease in hippocampal IL-1β level. The current study indicates for the first time that the loss of METH-related cognitive decline can be attenuated by neutralizing IL-1 signaling. Our findings suggest a potential new therapeutic pathway for treatment of altered cognitive abilities that occur in METH abusing individuals.

Original languageEnglish (US)
Pages (from-to)247-254
Number of pages8
JournalBrain, Behavior, and Immunity
Volume80
DOIs
StatePublished - Aug 2019

ASJC Scopus subject areas

  • Immunology
  • Endocrine and Autonomic Systems
  • Behavioral Neuroscience

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    Liśkiewicz, A., Przybyła, M., Park, M., Liśkiewicz, D., Nowacka-Chmielewska, M., Małecki, A., Barski, J., Lewin-Kowalik, J., & Toborek, M. (2019). Methamphetamine-associated cognitive decline is attenuated by neutralizing IL-1 signaling. Brain, Behavior, and Immunity, 80, 247-254. https://doi.org/10.1016/j.bbi.2019.03.016