TY - JOUR
T1 - Prefrontal cortex inflammation and liver pathologies accompany cognitive and motor deficits following Western diet consumption in non-obese female mice
AU - Veniaminova, Ekaterina
AU - Oplatchikova, Margarita
AU - Bettendorff, Lucien
AU - Kotenkova, Elena
AU - Lysko, Alexander
AU - Vasilevskaya, Ekaterina
AU - Kalueff, Allan V.
AU - Fedulova, Liliya
AU - Umriukhin, Aleksei
AU - Lesch, Klaus-Peter
AU - Anthony, Daniel C.
AU - Strekalova, Tatyana
N1 - Funding Information:
The authors' work reported here was supported by the European Community (the Horizon 2020 Research and Innovation Programme under Grant No. 728018 Eat2beNICE ), the “5-100” Russian Academic Excellence Project (to KPL and TS) and the Russian Science Foundation (RSF Grant No. 16-16-10073 to EK and LF). We appreciate valuable technical help of Anna Gorlova, Anastasiya Kibitkina, Galina Tolmacheva, Diana Babayevskaya and Igor Shafarevich with this project. LB is Research Director of the F.R.S.-FNRS (Belgium). Appendix A
Funding Information:
The authors' work reported here was supported by the European Community (the Horizon 2020 Research and Innovation Programme under Grant No. 728018 Eat2beNICE), the ?5-100? Russian Academic Excellence Project (to KPL and TS) and the Russian Science Foundation (RSF Grant No. 16-16-10073 to EK and LF). We appreciate valuable technical help of Anna Gorlova, Anastasiya Kibitkina, Galina Tolmacheva, Diana Babayevskaya and Igor Shafarevich with this project. LB is Research Director of the F.R.S.-FNRS (Belgium).
Publisher Copyright:
© 2019
PY - 2020/1/15
Y1 - 2020/1/15
N2 - Aims: The high sugar and lipid content of the Western diet (WD) is associated with metabolic dysfunction, non-alcoholic steatohepatitis, and it is an established risk factor for neuropsychiatric disorders. Our previous studies reported negative effects of the WD on rodent emotionality, impulsivity, and sociability in adulthood. Here, we investigated the effect of the WD on motor coordination, novelty recognition, and affective behavior in mice as well as molecular and cellular endpoints in brain and peripheral tissues.Main methods: Female C57BL/6 J mice were fed the WD for three weeks and were investigated for glucose tolerance, insulin resistance, liver steatosis, and changes in motor coordination, object recognition, and despair behavior in the swim test. Lipids and liver injury markers, including aspartate-transaminase, alanine-transaminase and urea were measured in blood. Serotonin transporter (SERT) expression, the density of Iba1-positive cells and concentration of malondialdehyde were measured in brain.Key findings: WD-fed mice exhibited impaired glucose tolerance and insulin resistance, a loss of motor coordination, deficits in novel object exploration and recognition, increased helplessness, dyslipidemia, as well as signs of a non-alcoholic steatohepatitis (NASH)-like syndrome: liver steatosis and increased liver injury markers. Importantly, these changes were accompanied by decreased SERT expression, elevated numbers of microglia cells and malondialdehyde levels in, and restricted to, the prefrontal cortex.Significance: The WD induces a spectrum of behaviors that are more reminiscent of ADHD and ASD than previously recognized and suggests that, in addition to the impairment of impulsivity and sociability, the consumption of a WD might be expected to exacerbate motor dysfunction that is also known to be associated with adult ADHD and ASD.
AB - Aims: The high sugar and lipid content of the Western diet (WD) is associated with metabolic dysfunction, non-alcoholic steatohepatitis, and it is an established risk factor for neuropsychiatric disorders. Our previous studies reported negative effects of the WD on rodent emotionality, impulsivity, and sociability in adulthood. Here, we investigated the effect of the WD on motor coordination, novelty recognition, and affective behavior in mice as well as molecular and cellular endpoints in brain and peripheral tissues.Main methods: Female C57BL/6 J mice were fed the WD for three weeks and were investigated for glucose tolerance, insulin resistance, liver steatosis, and changes in motor coordination, object recognition, and despair behavior in the swim test. Lipids and liver injury markers, including aspartate-transaminase, alanine-transaminase and urea were measured in blood. Serotonin transporter (SERT) expression, the density of Iba1-positive cells and concentration of malondialdehyde were measured in brain.Key findings: WD-fed mice exhibited impaired glucose tolerance and insulin resistance, a loss of motor coordination, deficits in novel object exploration and recognition, increased helplessness, dyslipidemia, as well as signs of a non-alcoholic steatohepatitis (NASH)-like syndrome: liver steatosis and increased liver injury markers. Importantly, these changes were accompanied by decreased SERT expression, elevated numbers of microglia cells and malondialdehyde levels in, and restricted to, the prefrontal cortex.Significance: The WD induces a spectrum of behaviors that are more reminiscent of ADHD and ASD than previously recognized and suggests that, in addition to the impairment of impulsivity and sociability, the consumption of a WD might be expected to exacerbate motor dysfunction that is also known to be associated with adult ADHD and ASD.
KW - Western diet
KW - Non-alcoholic steatohepatitis (NASH)
KW - Motor coordination
KW - Cognitive deficits
KW - Microglia
KW - Oxidative stress
KW - Prefrontal cortex
KW - Attention Deficit Hyperactivity Disorder (ADHD)
KW - Autism Spectrum Disorder (ASD)
KW - Mice
KW - ATTENTION-DEFICIT/HYPERACTIVITY DISORDER
KW - HIGH-FAT DIET
KW - TLR4 UP-REGULATION
KW - SEROTONIN TRANSPORTER
KW - OXIDATIVE STRESS
KW - MYOCARDIAL-INFARCTION
KW - DEPRESSION
KW - OBESITY
KW - CHOLESTEROL
KW - WEIGHT
U2 - 10.1016/j.lfs.2019.117163
DO - 10.1016/j.lfs.2019.117163
M3 - Article
C2 - 31837337
SN - 0024-3205
VL - 241
JO - Life Sciences
JF - Life Sciences
M1 - 117163
ER -