Exosomes: A Novel Therapeutic Paradigm for the Treatment of Depression

Abstract

Extracellular vesicles (EVs) of endocytic origin are known as exosomes. These vesicles are released by cells and are accessible in biofluids, such as saliva, urine, and plasma. These vesicles are made up of small RNA, DNA, proteins and play a vital role in many physiological processes. In central nervous system (CNS), they participate in various physiological processes such as stress of nerve cells, communication between the cells, synaptic plasticity and neurogenesis. The role of exosomes in depression needs to be explored further. It is known that exosomes can cross blood brain barrier (BBB), which is made up of glial cells astrocytes. One of the advantages of these vescicles is that they are able to transfer macromolecules like DNA, protein, mRNAs and miRNAs to recipient cells. This review focuses on the potential role of exosomes in de-pression and their utilization as atreatmentoption or diagnostic tool of depression.

Extracellular Vesicles: Emerging Roles in Developing Therapeutic Approach and Delivery Tool of Chinese Herbal Medicine for the Treatment of Depressive Disorder

“…Depending on the cellular sources, different subcellular components containing DNA, RNA, proteins, lipids, metabolites et al are delivered into recipient cells by EVs, which can effectively alter the biological response to diseases. The pathogenesis of depression mainly involves synaptic plasticity, oxidative stress, intestinal flora, dysregulation of the hypothalamic pituitary adrenal (HPA) axis, and altered neurotransmitter metabolism and neuroinflammation ( Bhatt et al, 2021 ; Zhang et al, 2021 ). Signal transmission from one nerve cell to another is essential for synaptic plasticity ( Chivet et al, 2012 ).…”

“…In this context, EVs could have advantages as drug vehicles, such as their small size, low immunogenicity, and ability to cross the BBB carrying cellular components or pharmacological agents (see Figure 3 ). Since EVs have the regenerative ability, they can also be exploited to potentially inhibit ongoing neurodegenerative processes associated with DD ( Bhatt et al, 2021 ). Previous researches have established the successful transmission of exosomes to the brain in mice via intranasal injection or intravenous administration ( Zhuang et al, 2011 ; Yuan et al, 2017 ).…”

“…Previous researches have established the successful transmission of exosomes to the brain in mice via intranasal injection or intravenous administration ( Zhuang et al, 2011 ; Yuan et al, 2017 ). Another study also showed that exosomes could pass over the BBB and communicate bi-directionally between the brain and the rest of body ( Bhatt et al, 2021 ). Despite the expected benefits of EVs for the treatment of DD, precise mechanisms of action and routes of delivery still require careful and rigorous investigation ( Bhatt et al, 2021 ).…”

“…Another study also showed that exosomes could pass over the BBB and communicate bi-directionally between the brain and the rest of body ( Bhatt et al, 2021 ). Despite the expected benefits of EVs for the treatment of DD, precise mechanisms of action and routes of delivery still require careful and rigorous investigation ( Bhatt et al, 2021 ).…”

“…The reasons why exosomes have the potential to be clinical diagnostics and biomarker are as follow ( Kanninen et al, 2016 ): Firstly, exosomal contents can be changed along with disease conditions, which can reflect the dynamic state of disease in real-time; Secondly, exosomes can be easily extracted non-invasively from biological fluids ( Bhatt et al, 2021 ), which is particular important because non-invasive availability is beneficial to early diagnosis of DD; Thirdly, exosomal contents are protected by the membranous structure, which keeps off the degradation of potential biomarkers ( Kanninen et al, 2016 ); Fourthly, exosomes are very stable and can be preserved for prolonged periods ( Grapp et al, 2013 ), making their clinical application feasible; Fifthly, exosomes can express their original cellular surface markers, so that they can be traced to their origin; Last but not least, since exosomes are able to pass over the BBB, which provide information of CNS cells that is hard to obtain without invasive techniques ( Boukouris and Mathivanan 2015 ; Kawikova and Askenase 2015 ; Lin et al, 2015 ; Aryani and Denecke 2016 ). Because exosomes are distributed in all biological fluids and all cells can secret them, their biogenesis enables the arresting of the complex extracellular and intracellular molecular cargo ( Kalluri and LeBleu 2020 ), rendering exosome-based liquid biopsy attractive in diagnosing the prognosis of DD.…”