Involvement of brain-derived neurotrophic factor signaling in the pathogenesis of stress-related brain diseases

Abstract

Neurotrophins including brain-derived neurotrophic factor, BDNF, have critical roles in neuronal differentiation, cell survival, and synaptic function in the peripheral and central nervous system. It is well known that a variety of intracellular signaling stimulated by TrkB, a high-affinity receptor for BDNF, is involved in the physiological and pathological neuronal aspects via affecting cell viability, synaptic function, neurogenesis, and cognitive function. As expected, an alteration of the BDNF/TrkB system is suspected to be one of the molecular mechanisms underlying cognitive decline in cognitive diseases and mental disorders. Recent evidence has also highlighted a possible link between the alteration of TrkB signaling and chronic stress. Furthermore, it has been demonstrated that downregulation of the BDNF/TrkB system and chronic stress have a role in the pathogenesis of Alzheimer’s disease (AD) and mental disorders. In this review, we introduce current evidence showing a close relationship between the BDNF/TrkB system and the development of cognition impairment in stress-related disorders, and the possible contribution of the upregulation of the BDNF/TrkB system in a therapeutic approach against these brain diseases.

An Interaction between Brain-Derived Neurotrophic Factor and Stress-Related Glucocorticoids in the Pathophysiology of Alzheimer’s Disease

“…Structurally, studies have shown that stress changes neuronal morphology and reduces neuronal proliferation and hippocampal volume [8]. Such dysregulation of the HPA axis has been suggested to be involved in the pathogenesis of not only mental disorders but also AD [9]. As expected, a variety of studies show that GCs affect neurons and induce neurobiological changes (molecular and cellular levels) via activation of their receptors, the glucocorticoid receptor (GR), or the mineralocorticoid receptor (MR).…”

“…However, after ND exposure, downregulated BDNF levels in the perinatal period and puberty (P40) were observed, suggesting that early-life DEX exposure caused interference in BDNF signaling during neuronal development [39]. A lot of evidence has shown the downregulation of the BDNF system after GC stress [9] (see Figure 1).…”

“…It is well known that the function of the HPA axis, which is critically important to cope with stressful conditions and strictly regulates blood levels of GCs, has been extensively studied, as dysregulation of the HPA axis has been suggested to be one of the risk factors in the pathogenesis of mental disorders and AD [9]. Importantly, secreted GCs from the adrenal glands, located on top of the kidneys, contribute to regulated blood levels of GCs via the negative feedback mechanism of the HPA axis.…”

“…The aggregated Aβ is thought to have neurotoxic effects, leading to abnormal phosphorylation of the tau protein, the subsequent formation of neurofibrillary tangles, the death of neurons, and the progressive cognitive decline observed in AD (Figure 2) [63]. While the disease's hallmark pathological features are the accumulation of Aβ plaques and neurofibrillary tangles, increasing attention has been directed toward understanding the role of BDNF dysregulation in AD pathophysiology [9,64].…”

The Effectiveness of Mindfulness in the Treatment of Methamphetamine Addiction Symptoms: Does Neuroplasticity Play a Role?

“…Mindfulness-induced increases in BDNF could potentially counteract or modulate these structural changes, offering protection against addiction-related neuroadaptations. Furthermore, chronic stress has been linked to alterations in BDNF-TrkB signaling [202], providing a potential link between mindfulness, stress reduction, and the modulation of neurotrophic factors in the context of methamphetamine dependency. By reducing stress, mindfulness may contribute to maintaining or enhancing BDNF expression, particularly in dopaminergic neurons, and counteract the negative impact of addictive drugs.…”