MgSO<sub>4</sub> alleviates anxiety-like behaviours in mice after traumatic brain injury by inhibiting astrocytic TRPM7 in the amygdala.
MgSO<sub>4</sub> may help reduce anxiety-like behaviors in mice after mild traumatic brain injury, but its relevance to human treatment is not established.
Where it sits
this study against the rest of the adamax corpusSummary and findings
This study investigated the effects of magnesium sulfate (MgSO<sub>4</sub>) on anxiety-like behaviors in male mice following mild traumatic brain injury (TBI). Mice received 100 mg/kg of MgSO<sub>4</sub> via intracerebroventricular injection. The results indicated that MgSO<sub>4</sub> administration reversed several behavioral and pathological deficits associated with TBI.
Abstract
<h4>Background</h4>Reports indicate anxiety as one of the most prevalent mental modifications that occur following traumatic brain injury (TBI). Transient Receptor Potential Melastatin 7 (TRPM7) is extensively distributed throughout the nervous system. It regulates intracellular homeostasis of calcium and magnesium ions, regulates the functions of glial cells, including astrocytes in the central nervous system, influences the inflammatory cascade, and may play a significant role in anxiety pathogenesis. However, the potential of astrocytic TRPM7 in the treatment of TBI-induced anxiety remains largely unexplored. The magnesium ion (Mg<sup>2+</sup>) is an essential endogenous neuroprotective agent in the brain. A previous study has demonstrated that magnesium sulphate (MgSO<sub>4</sub>) can markedly reduce TBI-induced neuroinflammation and possess neuroprotective effects. Nevertheless, the efficacy of MgSO<sub>4</sub> in alleviating anxiety is unclear. Therefore, this study utilised a rodent model of TBI to investigate whether MgSO<sub>4</sub> could mitigate anxiety-like behaviours following mild TBI by inhibiting astrocytic TRPM7.<h4>Methods</h4>Mild TBI was induced in male mice utilising the Feeney weight-drop paradigm with the rapid delivery of 2 μL of MgSO<sub>4</sub> (100 mg/kg) into the left lateral ventricle. Behavioural and pathological changes were assessed at various time intervals following injury utilising neurological severity score, the elevated plus-maze (EPM) test, and the open field test (OFT). Molecular and structural modifications were examined using transcriptomic analysis, real-time quantitative polymerase chain reaction, local field potential recordings, and immunofluorescence staining.<h4>Results</h4>Our findings revealed that mild TBI led to a diminished percentage of time spent in the central zone during the OFT, a reduced percentage of entries and time spent in the open arm during the EPM test, a decrease in the number of grid crossings, lowered serum Mg<sup>2+</sup> levels, and a reduction in θ and γ power and θ-γ phase coupling. Additionally, there was a decrease in the intensity of PSD95 and synaptophysin in the amygdala, a reduction in MAP2 intensity in the amygdala, an increase in GFAP and Iba1 intensity in the amygdala, enhanced cytoskeletal hypertrophy and radial extension of astrocytes, along with heightened colocalization of TRPM7 with GFAP in the amygdala, and enhanced colocalization of IL-1β with GFAP. Notably, MgSO<sub>4</sub> administration effectively reversed these pathological and functional deficits.<h4>Conclusions</h4>MgSO<sub>4</sub> mitigates anxiety-like behaviours in mice after mild TBI by inhibiting astrocytic TRPM7 in the amygdala, indicating a potential therapeutic approach for post-TBI anxiety.
Background
Anxiety is a common mental health issue following traumatic brain injury (TBI). Previous research has highlighted the role of Transient Receptor Potential Melastatin 7 (TRPM7) in the nervous system, particularly in relation to calcium and magnesium ion homeostasis. The potential of MgSO<sub>4</sub> as a neuroprotective agent in TBI-induced anxiety has not been thoroughly explored, making this study significant in addressing this gap.
Methods
Mild TBI was induced in male mice using the Feeney weight-drop paradigm. Mice received 2 μL of MgSO<sub>4</sub> (100 mg/kg) into the left lateral ventricle. Behavioral assessments included the neurological severity score, elevated plus-maze test, and open field test, with various molecular and structural analyses performed post-injury.
Results
The study reported a decrease in the time spent in the central zone of the open field test and reduced entries in the elevated plus-maze test following TBI. Additionally, serum Mg<sup>2+</sup> levels were lowered, and there were notable increases in GFAP and Iba1 intensity in the amygdala, indicating neuroinflammation.
Interpretation
The findings suggest that MgSO<sub>4</sub> may have a role in reversing anxiety-like behaviors post-TBI, although the clinical significance of these results remains uncertain. The study's reliance on a rodent model and lack of detailed statistical analysis may limit the applicability of the findings to human populations.
Key findings
- Diminished percentage of time spent in the central zone during the open field test after TBI.
- Reduced percentage of entries and time spent in the open arm during the elevated plus-maze test.
- Lowered serum Mg<sup>2+</sup> levels post-TBI.
- Increased GFAP and Iba1 intensity in the amygdala after TBI.
- Enhanced colocalization of TRPM7 with GFAP in the amygdala.
Limitations
- Rodent model limits human applicability.
- Sample size not reported.
- Specific statistical analyses not detailed.
- Short follow-up period not specified.