TRPV4 Deficiency Shifts Mitochondrial Dynamics Toward a Fragmented Morphology in Primary Microglia

Area of Science:

• Neuroscience
• Cell Biology
• Mitochondrial Dynamics

Background:

• Microglia are crucial for central nervous system (CNS) homeostasis, relying on energy-intensive processes like surveillance and phagocytosis.
• Mitochondria provide essential ATP for microglial functions, and their network structure influences microglial behavior.
• Transient Receptor Potential Vanilloid 4 (TRPV4) channels are known to regulate microglial morphology and migration, and are involved in mitochondrial calcium uptake.

Purpose of the Study:

• To investigate the role of Transient Receptor Potential Vanilloid 4 (TRPV4) in regulating the mitochondrial network within microglia.
• To determine if TRPV4 influences mitochondrial integrity and complexity in primary murine microglia.

Main Methods:

• Utilized primary murine microglia in vitro.
• Quantified mitochondrial fragmentation and complexity using the Mitochondrial Fragmentation and Complexity Index (MFCI).
• Assessed levels of phosphorylated dynamin-related protein 1 (pDrp1 Ser616) and mitochondrial distribution relative to the nucleus.

Main Results:

• Loss of TRPV4 (in Trpv4 knockout microglia) resulted in a fragmented mitochondrial network with reduced complexity.
• Significant differences in mitochondrial density were observed at distances of 10-32 µm from the nucleus in Trpv4 knockout versus wild-type microglia.
• Acute pharmacological inhibition of TRPV4 did not lead to significant mitochondrial network fragmentation.

Conclusions:

• Transient Receptor Potential Vanilloid 4 (TRPV4) channels play a significant role in maintaining the integrity and complexity of the mitochondrial network in microglia.
• TRPV4 is identified as a key regulator of mitochondrial dynamics and adaptive responses in microglia.
• These findings underscore the importance of TRPV4 in maintaining microglial and overall CNS homeostasis.