Mitochondria: A Connecting Link in the Major Depressive Disorder Jigsaw

Abstract

Mitochondria are integral to the function of neurons and undergo dysfunction in major depressive disorder patients. This dysfunction is reflected in all the various hypotheses that have been proposed for depression. Among the newer targets identified, which also involve mitochondria, includes the role of exogenous ATP. The diversity of purinergic receptors, and their differential expression among various individuals in the population, due to genetic and environmental (prenatal) influences, may influence the susceptibility and severity of depression. Identifying specific receptors involved and using patient-specific purinergic receptor antagonist may be an appropriate therapeutic course in the future.

Mangosteen Pericarp and Its Bioactive Xanthones: Potential Therapeutic Value in Alzheimer’s Disease, Parkinson’s Disease, and Depression with Pharmacokinetic and Safety Profiles

“…These findings strongly support critical roles of oxidative stress in the pathologies of AD, PD, and depression. Due to its direct relationship with oxidative stress, mitochondrial dysfunction also plays a key role in the pathogenesis of AD [ 63 ], PD [ 64 ], and depression [ 61 , 65 ]. Meanwhile, neurotrophic factors such as glial cell-derived neurotrophic factor, nerve growth factor, and especially, BDNF are crucial for survival, maintenance, and regeneration of specific neurons in the adult brain [ 66 ].…”

Clinical Evidence of Antidepressant Effects of Insulin and Anti-Hyperglycemic Agents and Implications for the Pathophysiology of Depression—A Literature Review

“…In addition, alterations in dopamine neurotransmission in the reward circuitry were also disrupted by a high-fat diet, inducing depressive-like behavior in mice through mediation of impaired brain insulin signaling [26]. The suggested mechanisms that mediate insulin signaling and dopaminergic neurotransmission, including mitochondrial dysfunction [95][96][97], oxidative stress [98][99][100], impaired leptin [101,102] and purinergic signaling [103], and disrupted dopaminergic neurotransmission [104], are known to play important roles in the pathophysiology of depression.…”

Mitochondria could be a potential key mediator linking the intestinal microbiota to depression

“…68 Chronic central administration of IL-1β in rats caused depressive-like symptoms. 22 On the other hand, inflammation has been well demonstrated to cause mitochondrial dysfunction. 70 In stressed rats, intracerebral infusion of RNAi against IL-1β ameliorated neuronal apoptosis and depression-like behaviors.…”

“…A recent study revealed that exogenous ATP released from damaged mitochondria can activate purinergic receptor to promote inflammation. 22 On the other hand, inflammation has been well demonstrated to cause mitochondrial dysfunction. In patients with sepsis, various indicators of mitochondrial function were decreased.…”

“…[19][20][21] Mitochondria have been considered to play key roles in these changes in depression. 20,22 Dysfunction of mitochondria has been well documented in various types of depression.…”