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Published on: May 12, 2015
Toll-like receptor-2 gene knockout results in neurobehavioral dysfunctions and multiple brain structural and
Yuting Hu1, Xiaoyu Sun1, Shang Wang1
1Department of Neurology, Affiliated Hospital of Xuzhou Medical University, China; Institute of Neurological Diseases, Xuzhou Medical University, China.
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.
Insights
Toll-like receptor-2 (TLR2) deficiency in mice impairs neurobehavioral functions, including cognition and motor activity, starting in middle age. This defect is linked to reduced cerebral blood flow, impaired synaptic function, and compromised blood-brain barrier integrity.
Area of Science:
- Neuroscience
- Immunology
- Genetics
Background:
- Toll-like receptor-2 (TLR2) is crucial for immune and inflammatory responses.
- TLR2 gene knockout (TLR2KO) mice are models for neurological diseases, but the specific impact of TLR2 deficiency on neurobehavior is unclear.
- Immune system and neurobehavioral functions are closely interconnected.
Purpose of the Study:
- To investigate the effect of TLR2 deficiency on neurobehavioral functions in mice.
- To elucidate the underlying mechanisms of TLR2 deficiency-induced neurobehavioral changes.
Main Methods:
- Neurobehavioral testing, Western blot, brain MRI, electrophysiological recording, and Evans blue assay were performed on TLR2KO and wild-type (WT) mice at 3, 7, and 12 months of age.
- Evaluated regional cerebral blood flow (rCBF), synaptic function (long-term potentiation - LTP), and blood-brain barrier (BBB) integrity.
- Assessed protein levels of tight junction proteins (ZO-1, Occludin, Claudin-5), neurofilament (SMI32), and myelin basic protein (MBP).
Main Results:
- TLR2KO mice exhibited decreased cognitive function, reduced locomotor activity, and increased anxiety from middle age onwards.
- Significantly reduced rCBF, inhibited LTP, and increased BBB permeability were observed in 12-month-old TLR2KO mice.
- Reduced tight junction proteins, increased neurofilament, and decreased myelin basic protein were found in TLR2KO mice at 7 and 12 months.
Conclusions:
- TLR2 deficiency causes significant neurobehavioral dysfunctions in mice, manifesting from middle age.
- These dysfunctions are associated with structural, functional, and molecular abnormalities in the brain.
- The study highlights the critical role of TLR2 in maintaining normal brain function and neurobehavior.
