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Updated: Jun 16, 2025
Isolation of Cortical Microglia with Preserved Immunophenotype and Functionality From Murine Neonates
Published on: January 30, 2014
The role of microglia in neuronal and cognitive function during high altitude acclimatization
Kathleen Hatch1,2,3,4, Fritz Lischka2,3, Mengfan Wang5
1Neuroscience Graduate Program, Uniformed Services University of the Health Sciences, Bethesda, MD, 20814, USA.
Abstract:
Due to their interactions with the neurovasculature, microglia are implicated in maladaptive responses to hypobaric hypoxia at high altitude (HA). To explore these interactions at HA, pharmacological depletion of microglia with the colony-stimulating factor-1 receptor inhibitor, PLX5622, was employed in male C57BL/6J mice maintained at HA or sea level (SL) for 3-weeks, followed by assessment of ex-vivo hippocampal long-term potentiation (LTP), fear memory recall and microglial dynamics/physiology. Our findings revealed that microglia depletion decreased LTP and reduced glucose levels by 25% at SL but did not affect fear memory recall. At HA, the absence of microglia did not significantly alter HA associated deficits in fear memory or HA mediated decreases in peripheral glucose levels. In regard to microglial dynamics in the cortex, HA enhanced microglial surveillance activity, ablation of microglia resulted in increased chemotactic responses and decreased microglia tip proliferation during ball formation. In contrast, vessel ablation increased cortical microglia tip path tortuosity. In the hippocampus, changes in microglial dynamics were only observed in response to vessel ablation following HA. As the hippocampus is critical for learning and memory, poor hippocampal microglial context-dependent adaptation may be responsible for some of the enduring neurological deficits associated with HA.
Insights
Microglia depletion impacted sea level learning but not high altitude memory deficits. Microglial adaptation in the hippocampus may be crucial for mitigating high altitude neurological issues.
Area of Science:
- Neuroscience
- High Altitude Physiology
- Cellular Biology
Background:
- Microglia interact with the neurovasculature and are implicated in maladaptive responses to hypobaric hypoxia at high altitude (HA).
- Understanding these interactions is crucial for addressing neurological deficits associated with HA exposure.
Purpose of the Study:
- To investigate the role of microglia in high altitude (HA)-induced neurological changes.
- To explore the impact of microglial depletion on learning, memory, and neurovascular interactions at HA and sea level (SL).
Main Methods:
- Pharmacological depletion of microglia using PLX5622 in male C57BL/6J mice.
- Mice were maintained at HA or SL for 3 weeks.
- Assessment of ex-vivo hippocampal long-term potentiation (LTP), fear memory recall, and microglial dynamics/physiology.
Main Results:
- Microglia depletion decreased LTP and reduced glucose levels by 25% at SL, but did not affect fear memory recall.
- At HA, microglial absence did not significantly alter HA-associated deficits in fear memory or HA-mediated decreases in peripheral glucose levels.
- HA enhanced microglial surveillance activity; microglia ablation increased chemotactic responses and decreased tip proliferation. Vessel ablation increased cortical microglia tip path tortuosity. Hippocampal microglial dynamics were altered by vessel ablation only after HA exposure.
Conclusions:
- Hippocampal microglia show poor context-dependent adaptation to HA, potentially contributing to enduring neurological deficits.
- Microglial function is critical for maintaining cognitive function and neurovascular integrity, particularly under stressful conditions like HA exposure.
