Trem2 expression in microglia is required to maintain normal neuronal bioenergetics during development

Area of Science:

• Neuroscience
• Cell Biology
• Genetics

Background:

• Triggering receptor expressed on myeloid cells 2 (Trem2) is crucial for microglia function and linked to neurodegenerative diseases.
• Trem2's role in neuronal development, particularly in shaping neuron bioenergetics, is not well understood.

Purpose of the Study:

• To investigate the role of Trem2 in regulating the bioenergetic profile and development of hippocampal pyramidal neurons.
• To determine if Trem2 influences neuronal maturation and mitochondrial function during development.

Main Methods:

• Analysis of Trem2's impact on neuronal metabolism and mitochondrial integrity in developing hippocampal neurons.
• Transcriptional profiling of hippocampal neurons to identify altered gene signatures related to metabolism and mitochondria.
• Assessment of neuronal maturation and organelle ultrastructure in the absence of Trem2.

Main Results:

• Absence of Trem2 led to compromised energetic metabolism, reduced mitochondrial mass, and abnormal organelle ultrastructure in developing CA1 hippocampal neurons.
• Transcriptional analysis revealed pervasive alterations in metabolic, oxidative phosphorylation, and mitochondrial gene expression in neonatal hippocampal neurons lacking Trem2.
• A delay in the maturation of CA1 neurons was observed in Trem2-deficient conditions.

Conclusions:

• Trem2 plays a critical role in controlling the bioenergetic fitness of developing pyramidal neurons in a region-specific manner.
• Trem2 regulates neuronal development by influencing metabolic processes and mitochondrial function within neurons, particularly in the CA1 hippocampal subfield.