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Assessing Spatial Memory Impairment in a Mouse Model of Traumatic Brain Injury Using a Radial Water Tread Maze
Published on: July 17, 2017
Spautin-1 administration mitigates mild TBI-induced cognitive and memory dysfunction in mice via activation of
Li-Min Zhang1, Dong-Xue Zhang2, Hui-Tao Miao3
1Department of Anesthesiology, Hebei Province Cangzhou Hospital of Integrated Traditional and Western Medicine (Cangzhou No. 2 Hospital), Cangzhou, China; Hebei Key Laboratory of Integrated Traditional and Western Medicine in Osteoarthrosis Research (Preparing), China.
Background:
Cognitive and memory dysfunction, a common sequela of traumatic brain injury (TBI), places a heavy social and economic burden on individuals, families, communities, and countries. Although the potent anti-tumor effects of spautin-1, a novel autophagy inhibitor, have been documented in malignant melanoma, little is known regarding its efficacy on alleviation of cognitive and memory dysfunction. Here, we describe the effect of spautin-1 administration on cognitive and memory impairment post-TBI, and reveal its underlying mechanism of action.
Methods:
We first induced mild TBI in mice through Feeney's weight-drop model, then immediately administered spautin-1 (10 mmol/μl, 2 μl) into the left lateral ventricle. Behavioral and pathological changes were assessed at 24 h, 7 and 30 days after TBI by analyzing neurological severity scores (NSS), novel objective recognition (NOR), Morris water maze (MWM) test, recording of local field potential (LFP), as well as western blot, and immunofluorescence assays.
Results:
Mild TBI not only reduced recognition index and times crossing platform, but also aggravated neuronal injury, including reduced MAP2, GAD2, VGlut2, and CHAT intensity. It also elevated activated microglia and CD86-occupied areas in TMEM119-positive cells, but suppressed θ, β, and γ oscillation power in the hippocampal CA1. However, spautin-1 administration significantly reversed these changes, whereas AC-DEVD-CHO an inhibitor of caspase-3 partially blocked the neuroprotective effects of spautin-1.
Conclusion:
Spautin-1 administration mitigates mild TBI-induced cognitive and memory dysfunction in mice, potentially through activation of caspase-3.
Insights
Spautin-1 effectively treats cognitive and memory deficits following traumatic brain injury (TBI) in mice. This autophagy inhibitor shows neuroprotective effects by potentially activating caspase-3.
Area of Science:
- Neuroscience
- Pharmacology
- Traumatic Brain Injury Research
Background:
- Traumatic brain injury (TBI) frequently causes cognitive and memory impairments, imposing significant societal and economic burdens.
- Spautin-1, a novel autophagy inhibitor, is known for anti-tumor effects but its impact on TBI-related cognitive dysfunction is largely unexplored.
Purpose of the Study:
- To investigate the efficacy of spautin-1 in alleviating cognitive and memory deficits after TBI in a mouse model.
- To elucidate the underlying mechanism of spautin-1's action in mitigating TBI-induced neurological damage.
Main Methods:
- Mild TBI was induced in mice using the Feeney weight-drop model, followed by intraventricular administration of spautin-1.
- Cognitive function was assessed using novel objective recognition and Morris water maze tests. Neurological severity, neuronal injury markers, microglial activation, and hippocampal oscillations were evaluated.
Main Results:
- TBI led to impaired recognition, reduced platform crossing, neuronal injury, increased microglial activation, and suppressed hippocampal oscillations.
- Spautin-1 administration significantly reversed these TBI-induced deficits.
- Caspase-3 inhibition partially counteracted the neuroprotective effects of spautin-1.
Conclusions:
- Spautin-1 demonstrates significant neuroprotective effects, mitigating cognitive and memory dysfunction in a mouse model of mild TBI.
- The findings suggest that spautin-1's therapeutic potential in TBI may involve the activation of caspase-3.
