TY - JOUR
T1 - Toll-like receptor-2 gene knockout results in neurobehavioral dysfunctions and multiple brain structural and functional abnormalities in mice
AU - Hu, Yuting
AU - Sun, Xiaoyu
AU - Wang, Shang
AU - Zhou, Chao
AU - Lin, Li
AU - Ding, Xiaohui
AU - Han, Jingjing
AU - Zhou, Yan
AU - Jin, Guoliang
AU - Wang, Yuqiao
AU - Zhang, Wei
AU - Shi, Hongjuan
AU - Zhang, Zuohui
AU - Yang, Xinxin
AU - Hua, Fang
N1 - Publisher Copyright:
© 2020 The Authors
PY - 2021/1
Y1 - 2021/1
N2 - Objective: Toll-like receptor-2 (TLR2), a member of TLR family, plays an important role in the induction and regulation of immune/inflammation. TLR2 gene knockout (TLR2KO) mice have been widely used for animal models of neurological diseases. Since there is close relationship between immune system and neurobehavioral functions, it is important to clarify the exact role of TLR2 defect itself in neurobehavioral functions. The present study aimed to investigate the effect of TLR2KO on neurobehavioral functions in mice and the mechanisms underlying the observed changes. Methods: Male TLR2KO and wild type (WT) mice aged 3, 7, and 12 months were used for neurobehavioral testing and detection of protein expression by Western blot. Brain magnetic resonance imaging (MRI), electrophysiological recording, and Evans blue (EB) assay were applied to evaluate regional cerebral blood flow (rCBF), synaptic function, and blood–brain barrier (BBB) integrity in 12-month-old TLR2KO and age-matched WT mice. Results: Compared to WT mice, TLR2KO mice showed decreased cognitive function and locomotor activity, as well as increased anxiety, which developed from middle age (before 7-month-old) to old age. In addition, significantly reduced regional cerebral blood flow (rCBF), inhibited long-term potentiation (LTP), and increased blood–brain barrier (BBB) permeability were observed in 12-month-old TLR2KO mice. Furthermore, compared with age-matched WT mice, significant reduction in protein levels of tight junction proteins (ZO-1, Occludin, and Claudin-5) and increased neurofilament protein (SMI32) were observed in 7 and 12-month-old TLR2KO mice, and that myelin basic protein (MBP) decreased in 12-month-old TLR2KO mice. Conclusion: Our data demonstrated that TLR2 defect resulted in significantly observable neurobehavioral dysfunctions in mice starting from middle age, as well as multiple abnormalities in brain structure, function, and molecular metabolism.
AB - Objective: Toll-like receptor-2 (TLR2), a member of TLR family, plays an important role in the induction and regulation of immune/inflammation. TLR2 gene knockout (TLR2KO) mice have been widely used for animal models of neurological diseases. Since there is close relationship between immune system and neurobehavioral functions, it is important to clarify the exact role of TLR2 defect itself in neurobehavioral functions. The present study aimed to investigate the effect of TLR2KO on neurobehavioral functions in mice and the mechanisms underlying the observed changes. Methods: Male TLR2KO and wild type (WT) mice aged 3, 7, and 12 months were used for neurobehavioral testing and detection of protein expression by Western blot. Brain magnetic resonance imaging (MRI), electrophysiological recording, and Evans blue (EB) assay were applied to evaluate regional cerebral blood flow (rCBF), synaptic function, and blood–brain barrier (BBB) integrity in 12-month-old TLR2KO and age-matched WT mice. Results: Compared to WT mice, TLR2KO mice showed decreased cognitive function and locomotor activity, as well as increased anxiety, which developed from middle age (before 7-month-old) to old age. In addition, significantly reduced regional cerebral blood flow (rCBF), inhibited long-term potentiation (LTP), and increased blood–brain barrier (BBB) permeability were observed in 12-month-old TLR2KO mice. Furthermore, compared with age-matched WT mice, significant reduction in protein levels of tight junction proteins (ZO-1, Occludin, and Claudin-5) and increased neurofilament protein (SMI32) were observed in 7 and 12-month-old TLR2KO mice, and that myelin basic protein (MBP) decreased in 12-month-old TLR2KO mice. Conclusion: Our data demonstrated that TLR2 defect resulted in significantly observable neurobehavioral dysfunctions in mice starting from middle age, as well as multiple abnormalities in brain structure, function, and molecular metabolism.
KW - Blood-brain barrier
KW - Neurobehavioral function
KW - Synaptic function
KW - TLR2
KW - rCBF
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U2 - 10.1016/j.bbi.2020.10.004
DO - 10.1016/j.bbi.2020.10.004
M3 - Article
C2 - 33069798
AN - SCOPUS:85094174675
SN - 0889-1591
VL - 91
SP - 257
EP - 266
JO - Brain, Behavior, and Immunity
JF - Brain, Behavior, and Immunity
ER -