TY - JOUR
T1 - Methamphetamine-associated cognitive decline is attenuated by neutralizing IL-1 signaling
AU - Liśkiewicz, Arkadiusz
AU - Przybyła, Marta
AU - Park, Minseon
AU - Liśkiewicz, Daniela
AU - Nowacka-Chmielewska, Marta
AU - Małecki, Andrzej
AU - Barski, Jarosław
AU - Lewin-Kowalik, Joanna
AU - Toborek, Michal
N1 - Funding Information:
The study was supported in part by the National Science Centre (NSC) grant 2015/17/B/NZ7/02985 and the National Institutes of Health (NIH), grants DA039576 , DA040537 , DA044579 , MH098891 , MH072567 , and HL126559 .
PY - 2019/8
Y1 - 2019/8
N2 - 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.
AB - 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.
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U2 - 10.1016/j.bbi.2019.03.016
DO - 10.1016/j.bbi.2019.03.016
M3 - Article
C2 - 30885840
AN - SCOPUS:85063222032
VL - 80
SP - 247
EP - 254
JO - Brain, Behavior, and Immunity
JF - Brain, Behavior, and Immunity
SN - 0889-1591
ER -