Deletion of CaMKIIα disrupts glucose metabolism, glutamate uptake, and synaptic energetics in the cerebral cortex
Journal of neurochemistry(2024)
Abstract
Ca2+/calmodulin-dependent protein kinase II alpha (CaMKIIa) is a key regulator of neuronal signaling and synaptic plasticity. Synaptic activity and neurotransmitter homeostasis are closely coupled to the energy metabolism of both neurons and astrocytes. However, whether CaMKIIa function is implicated in brain energy and neurotransmitter metabolism remains unclear. Here, we explored the metabolic consequences of CaMKIIa deletion in the cerebral cortex using a genetic CaMKIIa knockout (KO) mouse. Energy and neurotransmitter metabolism was functionally investigated in acutely isolated cerebral cortical slices using stable C-13 isotope tracing, whereas the metabolic function of synaptosomes was assessed by the rates of glycolytic activity and mitochondrial respiration. The oxidative metabolism of [U-C-13]glucose was extensively reduced in cerebral cortical slices of the CaMKIIa KO mice. In contrast, metabolism of [1,2-C-13]acetate, primarily reflecting astrocyte metabolism, was unaffected. Cellular uptake, and subsequent metabolism, of [U-C-13]glutamate was decreased in cerebral cortical slices of CaMKIIa KO mice, whereas uptake and metabolism of [U-C-13]GABA were unaffected, suggesting selective metabolic impairments of the excitatory system. Synaptic metabolic function was maintained during resting conditions in isolated synaptosomes from CaMKIIa KO mice, but both the glycolytic and mitochondrial capacities became insufficient when the synaptosomes were metabolically challenged. Collectively, this study shows that global deletion of CaMKIIa significantly impairs cellular energy and neurotransmitter metabolism, particularly of neurons, suggesting a metabolic role of CaMKIIa signaling in the brain.
MoreTranslated text
Key words
astrocytes,Ca(2+/)calmodulin-dependent protein kinase II alpha,energy and neurotransmitter metabolism,long-term potentiation,mitochondria,neurotransmitter recycling
AI Read Science
Must-Reading Tree
Example
![](https://originalfileserver.aminer.cn/sys/aminer/pubs/mrt_preview.jpeg)
Generate MRT to find the research sequence of this paper
Chat Paper
Summary is being generated by the instructions you defined