Purinergic Signaling and Energy Homeostasis in Psychiatric Disorders

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.

Hyperuricemia in Children and Adolescents with Autism Spectrum Disorder Treated with Risperidone: The Risk Factors for Metabolic Adverse Effects

“…A higher dose of risperidone and/or a longer treatment time are associated with higher levels of serum uric acid. However, the previous studies reported that Mitochondrial and purinergic dysfunction have been associated with ASD (Frye, 2015; Lindberg et al, 2015). As shown by Chauhan et al (2011), the frontal lobe, cerebellum, and temporal lobe in post-mortem brains of children with autism had diminished expression of mitochondrial electron transport chain proteins.…”

“…An excessive amount of uric acid is considered to be a mediator of proinflammatory endocrine imbalance in adipose tissue, contributing to the development of dyslipidemia and low-grade inflammation (Baldwin et al, 2011). Patients with autism spectrum disorder (ASD) may have increased levels of uric acid (Page and Coleman, 2000; Jinnah et al, 2013; Lindberg et al, 2015). Mitochondrial and purinergic dysfunction have been associated with mental illnesses such as bipolar disorder, ASD, and schizophrenia (Lindberg et al, 2015).…”

“…Patients with autism spectrum disorder (ASD) may have increased levels of uric acid (Page and Coleman, 2000; Jinnah et al, 2013; Lindberg et al, 2015). Mitochondrial and purinergic dysfunction have been associated with mental illnesses such as bipolar disorder, ASD, and schizophrenia (Lindberg et al, 2015). A previous study found increased levels of serum uric acid in adolescent patients with bipolar mania when treated with an atypical antipsychotic, olanzapine (Tohen et al, 2007).…”

Evidence of Mitochondrial Dysfunction in Autism: Biochemical Links, Genetic‐Based Associations, and Non‐Energy‐Related Mechanisms

“…Neurotransmitter-mediated calcium signaling is important for the recruitment and accumulation of mitochondria to postsynaptic regions, a process that is critical for neuronal calcium buffering and synapse strength [111]. Calcium signaling is important for neurotransmitter release from presynaptic neurons as well as signaling in postsynaptic neurons in response to neurotransmitters such glutamate and γ -aminobutyric acid (GABA) [111, 112].…”

“…Calcium signaling is important for neurotransmitter release from presynaptic neurons as well as signaling in postsynaptic neurons in response to neurotransmitters such glutamate and γ -aminobutyric acid (GABA) [111, 112]. Glutamate receptors are ligand-gated calcium channels while GABA receptors trigger calcium influx via voltage-gated calcium channels [112].…”