Phytochemicals That Act on Synaptic Plasticity as Potential Prophylaxis against Stress-Induced Depressive Disorder

Abstract

Depression is a neuropsychiatric disorder associated with persistent stress and disruption of neuronal function. Persistent stress causes neuronal atrophy, including loss of synapses and reduced size of the hippocampus and prefrontal cortex. These alterations are associated with neural dysfunction, including mood disturbances, cognitive impairment, and behavioral changes. Synaptic plasticity is the fundamental function of neural networks in response to various stimuli and acts by reorganizing neuronal structure, function, and connections from the molecular to the behavioral level. In this review, we describe the alterations in synaptic plasticity as underlying pathological mechanisms for depression in animal models and humans. We further elaborate on the significance of phytochemicals as bioactive agents that can positively modulate stress-induced, aberrant synaptic activity. Bioactive agents, including flavonoids, terpenes, saponins, and lignans, have been reported to upregulate brain-derived neurotrophic factor expression and release, suppress neuronal loss, and activate the relevant signaling pathways, including TrkB, ERK, Akt, and mTOR pathways, resulting in increased spine maturation and synaptic numbers in the neuronal cells and in the brains of stressed animals. In clinical trials, phytochemical usage is regarded as safe and well-tolerated for suppressing stress-related parameters in patients with depression. Thus, intake of phytochemicals with safe and active effects on synaptic plasticity may be a strategy for preventing neuronal damage and alleviating depression in a stressful life.

Long-term environmental enrichment overcomes depression, learning, and memory impairment in elderly CD-1 mice with maternal sleep deprivation exposure

“…The hippocampus is an important region of the limbic system associated with depression and cognitive function ( Jia et al, 2023 ; Yoon et al, 2023 ). Under stimulation of various pathological factors, hippocampal immune cells release large amounts of proinflammatory cytokines that contribute to neuroinflammation, which could increase the risk of depression and cognitive decline ( Wu et al, 2021 ; Hao et al, 2022 ).…”

Targeting the p53 signaling pathway in cancers: Molecular mechanisms and clinical studies

“…TSC2 is transcriptionally regulated by p53, activated by AMPK, inhibits the mTOR signaling pathway, and plays a key role in regulating cellular energy metabolism 242,243 . The mammalian target of rapamycin (mTOR), a class of serine/threonine kinases, is an intracellular signaling molecule 244 . Abnormal activation of mTOR signaling can lead to multiple adverse outcomes, including tumor formation, neonatal insulin resistance, and adipogenesis 245 .…”

“… 242 , 243 The mammalian target of rapamycin (mTOR), a class of serine/threonine kinases, is an intracellular signaling molecule. 244 Abnormal activation of mTOR signaling can lead to multiple adverse outcomes, including tumor formation, neonatal insulin resistance, and adipogenesis. 245 Inactivating mutations in TSC2 cause hamartomas primarily in multiple organ systems.…”

The influence of stress on mental health among Chinese college students: The moderating role of psychological suzhi

“…Studies have demonstrated that chronic stress can cause a series of psychological problems, with the cumulative effect of stressors serving as a significant predictor of symptoms associated with depression and anxiety [ [2] , [3] , [4] ]. Prolonged exposure to stress induces neuronal atrophy, which is characterized by synaptic loss and diminished volume in the hippocampus and prefrontal cortices, potentially leading to mood disorders, cognitive impairments, and behavioral alterations [ 5 ]. In addition to chronic stress accumulated over an extended duration, college students also encounter various acute stressful events, such as examinations or emergencies.…”