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Updated: Jul 14, 2026
Assessing Changes in Synaptic Plasticity Using an Awake Closed-Head Injury Model of Mild Traumatic Brain Injury
Published on: January 20, 2023
Loss of TREM2 is associated with altered microglial responses and inhibitory synaptic changes after closed head
Duan Wang1, Donghui Lin2, Jiayu Liu2
1Department of Rehabilitation, Zhangzhou Affiliated Hospital of Fujian Medical University, Zhangzhou, Fujian province, China; Department of Rehabilitation, Children's Hospital of Chongqing Medical University, Chongqing, China; National Clinical Research Center for Child Health and Disorders, Chongqing, China; Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing, China; Chongqing Key Laboratory of Child Neurodevelopment and Cognitive Disorders, Chongqing, China.
Abstract:
Closed head injury (CHI) is often considered to cause mild brain injury without overt cortical lesions. However, synaptic pathology following CHI, particularly in different phase, remains poorly understood. In this study, we investigate temporal changes in synaptic protein expression and microglial responses following CHI. Our results show a selective loss of inhibitory presynaptic marker vGAT, accompanied by transient increases in excitatory postsynaptic markers PSD-95 and gephyrin. Notably, these changes occur alongside a peak in microglial activation at 3 days post-injury (dpi). Bulk RNA sequencing analysis identified TREM2 as a prominently upregulated microglia-associated gene during the acute phase of injury. Loss of TREM2 in knockout mice (TREM2-/-) resulted in attenuated microglial activation, impaired accumulation at the injury site, and reduced expression of response-related genes, including Cx3cr1 and Cd68. Additionally, C1q, a key component in synaptic pruning, exhibited altered expression and spatial distribution in TREM2-deficient mice, suggesting a potential TREM2-dependent role in regulating microglial responses and synaptic alterations after CHI. These findings highlight TREM2 as a critical modulator of microglial function and synaptic remodeling following brain injury.
Insights
Closed head injury (CHI) causes synaptic changes, with TREM2 signaling crucial for microglial responses and synaptic remodeling. This study reveals TREM2
Area of Science:
- Neuroscience
- Neurotrauma
- Immunology
Background:
- Closed head injury (CHI) can cause subtle synaptic pathology, but its temporal dynamics and underlying mechanisms are unclear.
- Understanding microglial involvement in CHI-induced synaptic alterations is critical for developing therapeutic strategies.
Purpose of the Study:
- To investigate the temporal changes in synaptic protein expression and microglial activation following CHI.
- To elucidate the role of TREM2 in mediating microglial responses and synaptic remodeling after CHI.
Main Methods:
- Utilized a mouse model of CHI to analyze temporal changes in synaptic markers (vGAT, PSD-95, gephyrin) and microglial activation.
- Performed bulk RNA sequencing to identify key genes, including TREM2, upregulated in microglia post-injury.
- Investigated the impact of TREM2 deficiency (TREM2-/- mice) on microglial responses, gene expression (Cx3cr1, Cd68), and C1q distribution.
Main Results:
- Observed selective loss of inhibitory vGAT and transient increases in excitatory PSD-95 and gephyrin post-CHI.
- Microglial activation peaked at 3 days post-injury, coinciding with TREM2 upregulation.
- TREM2 deficiency attenuated microglial activation, impaired their accumulation at the injury site, and altered C1q expression and distribution.
Conclusions:
- TREM2 plays a critical role in modulating microglial activation and synaptic remodeling following CHI.
- TREM2 influences the expression of microglial response genes and synaptic pruning components like C1q.
- Targeting TREM2 may offer a therapeutic avenue for mitigating synaptic pathology after brain injury.
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