Heart-brain axis, gliotransmitters and peripheral neurogenesis: Emerging regenerative roles of cardiac nexus glia in health and disease

Abstract

The heart and brain are functionally synchronized through the heart-brain axis, also known as the neurocardiac axis. Astrocytes are the predominant subpopulation of glial cells in the central nervous system that play an integral role in maintaining homeostasis, neurovascular coupling, and synaptic transmission. Radial astroglia are recognized as a potential source for the generation of new neurons in the brain, a process known as neurogenesis, accounting for neuroplasticity. While brain-resident astrocytes have been extensively studied, increasing experimental evidence has demonstrated the presence of astroglial-like cells in various organs, including the heart. The existence of astrocyte-like cells in the heart, known as cardiac nexus glia, is recognized as an emerging key modulator of cardiac function and blood flow. Similar to astrocytes, cardiac nexus glia can also release different gliotransmitters, including brain-derived neurotrophic factor, thereby modulating neurocardiac interactions. This review delves into the mechanistic insights of the cardiac nexus glia and emphasizes a hypothesis that these glial cells may possess the multipotent capacity to generate neurons, astrocytes, and oligodendrocytes, suggesting that peripheral neurogenesis could occur in the heart. As astrocytes are vital for neuroplasticity, the regulation of cardiac nexus glia may support heart–brain communication, while their dysfunction could lead to neurocardiac disorders.

Keywords: Heart-brain-axis; Cardiac nexus glia; Neuroplasticity; Astrocytes; Gliotransmitters; Neuroregeneration

Core Tip: Cardiac nexus cells are a specialized cell type in the heart that exhibit phenotypic similarities to astrocytes in the brain. As radial glia-like astrocytes serve as multipotent neural stem cells, cardiac nexus cells may differentiate into neurons, astrocytes, and oligodendrocytes. This article introduces a novel concept of peripheral neurogenesis, proposing that neurogenic activity originates outside the central nervous system, especially in the heart. Eventually, cardiac nexus cells could contribute to the neurocardiac axis through the release of gliotransmitters and regulate neurogenesis in the brain, while their dysfunction could be associated with neurocardiac disorders.