Title:Purinergic Signaling and Energy Homeostasis in Psychiatric Disorders
Volume: 15
Issue: 3
Author(s): D. Lindberg, D. Shan, J. Ayers-Ringler, A. Oliveros, J. Benitez, M. Prieto, R. McCullumsmith and D.-S. Choi
Affiliation:
Keywords:
Adenosine, ATP, energy homeostasis, mental disorders, mitochondria, glutamate, purine.
Abstract: Purinergic signaling regulates numerous vital biological processes in the central
nervous system (CNS). The two principle purines, ATP and adenosine act as excitatory and
inhibitory neurotransmitters, respectively. Compared to other classical neurotransmitters, the role
of purinergic signaling in psychiatric disorders is not well understood or appreciated. Because ATP exerts its main
effect on energy homeostasis, neuronal function of ATP has been underestimated. Similarly, adenosine is primarily
appreciated as a precursor of nucleotide synthesis during active cell growth and division. However, recent
findings suggest that purinergic signaling may explain how neuronal activity is associated neuronal energy
charge and energy homeostasis, especially in mental disorders. In this review, we provide an overview of the
synaptic function of mitochondria and purines in neuromodulation, synaptic plasticity, and neuron-glia interactions.
We summarize how mitochondrial and purinergic dysfunction contribute to mental illnesses such as schizophrenia,
bipolar disorder, autism spectrum disorder (ASD), depression, and addiction. Finally, we discuss future implications
regarding the pharmacological targeting of mitochondrial and purinergic function for the treatment of psychiatric
disorders.