Details

Autor(en) / Beteiligte

• Hu, Yuting
• Sun, Xiaoyu
• Wang, Shang
• Zhou, Chao
• Lin, Li
• Ding, Xiaohui
• Han, Jingjing
• Zhou, Yan
• Jin, Guoliang
• Wang, Yuqiao
• Zhang, Wei
• Shi, Hongjuan
• Zhang, Zuohui
• Yang, Xinxin
• Hua, Fang

Titel

Toll-like receptor-2 gene knockout results in neurobehavioral dysfunctions and multiple brain structural and functional abnormalities in mice

Ist Teil von

• Brain, behavior, and immunity, 2021-01, Vol.91, p.257-266

Ort / Verlag

Netherlands: Elsevier Inc

Erscheinungsjahr

2021

Quelle

Elsevier ScienceDirect Journals

Beschreibungen/Notizen

• •TLR2 gene knockout leads to neurobehavioral dysfunction in mice, which appears in middle age and develops into old age.•TLR2 defect decreases synapse long-term potentiation in hippocampus in mice.•TLR2 defect results in cerebral cortical hypoperfusion and white matter lesions in mouse brain.•TLR2 defect induces compromised blood brain barrier integrity in mice. 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. 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. 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. 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.