Depression Plasticity Research Articles

Disembodiment and Affective Resonances in Esketamine Treatment of Depersonalized Depression Subtype: Two Case Studies

Introduction: Dissociative experiences are considered undesirable ketamine’s adverse events. However, they might be crucial for ketamine’s antidepressant effects, at least in some depression subtypes. Current understandings of ketamine’s therapeutic potentials converge on the so-called “relaxed prior hypothesis,” suggesting that glutamatergic blockage up-weights bottom-up surprising somatosensory/affective states. As a result, ketamine improves short-term plasticity in depression by enhancing sensitivity to interoceptive signals. Methods: We selected 2 case studies for their paradigmatic description of “depersonalized depression” (Entfremdungsdepression) symptoms. Patients were included in a 6-month-long esketamine program for treatment resistant depression, during which we collected their spontaneous experience with esketamine. According to a neurophenomenological approach, we combined subjective reports from unstructured clinical interviews and the review of previous objective neuroimaging results and neurocomputational models to unveil the relation between esketamine antidepressant effects and interoceptive sensitivity. Results: According to our clinical observations, esketamine-induced dissociation might be particularly effective in the depersonalized depression subtype, in which interoceptive awareness and interaffectivity are particularly compromised. Ketamine and esketamine’s dissociative effects and particularly disembodiment might suspend previously acquired patterns of feeling, sensing, and behaving. Conclusions: Coherently with previous research, we suggest that esketamine-induced disembodiment allows for a transient window of psychological plasticity and enhanced sensitivity, where the body recovers its permeability to affective affordances.

The role of Neurotrophin 3 (NT-3) on neural plasticity in depression: a literature review

Background: Major Depressive Disorder (MDD) is a pervasive global health concern characterized by complex interactions between genetic and environmental factors, resulting in structural and functional alterations within the brain. This abstract explores the involvement of neurotrophin-3 (NT-3) in MDD, shedding light on its potential as a therapeutic target. Neuroanatomical evidence implicates brain regions like the amygdala, hippocampus, prefrontal cortex, and ventral striatum in MDD pathology, with aberrant synaptic plasticity and neurogenesis playing a crucial role. Methods: We conducted a review using a systematic search of MEDLINE. The results of the studies that match the search criteria are then analyzed using a narrative synthesis to include in the literature review. Results: There are four known brain regions and neurocircuits that are involved in depression, which are amygdala, hippocampus, prefrontal cortex, and ventral striatum. NT-3, a member of the neurotrophin family, has emerged as a critical modulator of depressive processes, whereas NT-3 influences monoamine neurotransmitters, serotonin, and noradrenaline while also regulating synaptic plasticity, neurogenesis, brain-derived neurotrophic factor signaling, and the hypothalamic-pituitary-adrenal (HPA) axis. Conclusion: NT-3 emerges as a promising therapeutic target for MDD, with multifaceted effects on neurotransmitters, synaptic plasticity, neurogenesis, and the HPA axis. However, further preclinical and clinical studies are needed to comprehensively evaluate its potential in managing mood disorders.

Perinatal Depression and the Role of Synaptic Plasticity in Its Pathogenesis and Treatment.

Emerging evidence indicates that synaptic plasticity is significantly involved in the pathophysiology and treatment of perinatal depression. Animal models have demonstrated the effects of overstimulated or weakened synapses in various circuits of the brain in causing affective disturbances. GABAergic theory of depression, stress, and the neuroplasticity model of depression indicate the role of synaptic plasticity in the pathogenesis of depression. Multiple factors related to perinatal depression like hormonal shifts, newer antidepressants, mood stabilizers, monoamine systems, biomarkers, neurotrophins, cytokines, psychotherapy and electroconvulsive therapy have demonstrated direct and indirect effects on synaptic plasticity. In this review, we discuss and summarize the various patho-physiology-related effects of synaptic plasticity in depression. We also discuss the association of treatment-related aspects related to psychotropics, electroconvulsive therapy, neuromodulation, psychotherapy, physical exercise and yoga with synaptic plasticity in perinatal depression. Future insights into newer methods of treatment directed towards the modulation of neuroplasticity for perinatal depression will be discussed.

Simvastatin ameliorates synaptic plasticity impairment in chronic mild stress-induced depressed mice by modulating hippocampal NMDA receptor.

In our previous study, we showed simvastatin exerts an antidepressant effect and inhibits neuroinflammation. Given the role of synaptic impairment in depression development, we investigate the effect of simvastatin on synaptic plasticity in depression and the related mechanisms. Electrophysiological analysis, Golgi staining, and transmission electron microscope were performed to analyze the effect of simvastatin on synaptic impairment in depression. In addition, the localization and reactivity of N-methyl-D-aspartate receptor (NMDAR) subunits and the downstream signaling were investigated to explore the mechanism of simvastatin's effect on synaptic plasticity. Simvastatin ameliorated the reduction of the magnitude of long-term potentiation (LTP) in Schaffer collateral-CA1, restored hippocampal dendritic spine density loss, improved the number of spine synapses, reversed the reduction in BrdU-positive cells in chronic mild stress (CMS)-induced depressed mice, and ameliorated NMDA-induced neurotoxicity in hippocampal neurons. Dysfunction of NMDAR activity in the hippocampus is associated with depression. Simvastatin treatment reversed the surface expression and phosphorylation changes of NMDAR subunits in NMDA-treated hippocampal neurons and depressed mice. In addition, simvastatin further increased the levels of mature BDNF, activating TrkB-Akt-mTOR signaling, which is critical for synaptic plasticity. These findings suggest that simvastatin can improve the dysfunction of NMDAR and ameliorate hippocampal synaptic plasticity impairment in depressed mice.

Acupuncture Alleviates CUMS-Induced Depression-Like Behaviors by Restoring Prefrontal Cortex Neuroplasticity.

To explore the therapeutic efficiency of acupuncture and the related molecular mechanism of neural plasticity in depression. Chronic unpredictable mild stress- (CUMS-) induced rats were established for the depression animal model. There were a total of four rat groups, including the control group, the CUMS group, the CUMS+acupuncture group, and the CUMS+fluoxetine group. The acupuncture group and the fluoxetine group were given a 3-week treatment after the modeling intervention. The researcher performed the open-field, elevated plus maze, and sucrose preference tests to evaluate depressive behaviors. The number of nerve cells, dendrites' length, and the prefrontal cortex's spine density were detected using Golgi staining. The prefrontal cortex expression, such as BDNF, PSD95, SYN, and PKMZ protein, was detected using the western blot and RT-PCR. Acupuncture could alleviate depressive-like behaviors and promote the recovery of the neural plasticity functions in the prefrontal cortex, showing the increasing cell numbers, prolonging the length of the dendrites, and enhancing the spine density. The neural plasticity-related proteins in the prefrontal cortex, including BDNF, PSD95, SYN, and PKMZ, were all downregulated in the CUMS-induced group; however, these effects could be partly reversed after being treated by acupuncture and fluoxetine (P < 0.05). Acupuncture can ameliorate depressive-like behaviors by promoting the recovery of neural plasticity functions and neural plasticity-related protein upregulation in the prefrontal cortex of CUMS-induced depressed rats. Our study provides new insights into the antidepressant approach, and further studies are warranted to elucidate the mechanisms of acupuncture involved in depression treatment.

Ginsenoside-Rg1 synergized with voluntary running exercise protects against glial activation and dysregulation of neuronal plasticity in depression.

Depression is a common psychological disease accompanied by mental disorders and somatic symptoms. However, the underlying mechanisms regarding the pathogenesis of depression are still not clear. Neuronal damage resulting from inflammation is considered to be one of the important risk factors for depression. Ginsenoside-Rg1, a sterol extract extracted from ginseng herbs, has been shown to have neuroprotective effects against neurodegenerative diseases. Moreover, running exercise, a simple behavioral therapy, has been recently shown to have antidepressant effects. However, whether these two synergized strategies are more efficient in depression treatment, especially the neural mechanisms underlying this practical and interesting treatment is unknown. In this study, we have shown that ginsenoside-Rg1 synergized with voluntary running exercise exerts more efficiency on suppressing neuroinflammation, up-regulating expression of neurotrophic factors, and synaptic-related proteins, ameliorating neuronal structural damages than that of ginsenoside-Rg1 or voluntary exercise alone, suggesting its better neuroprotective effects. More importantly, the antidepressant-like effect of this synergistic treatment was also significantly better than either of these two treatments. These results suggest that ginsenoside-Rg1, synergized with voluntary running, may have higher efficacy in the treatment of depression through anti-inflammation and the improvement of neuroplasticity. These findings may provide a new perspective for the development of a therapeutic strategy for depression.

M6A RNA Methylation-Based Epitranscriptomic Modifications in Plasticity-Related Genes via miR-124-C/EBPα-FTO-Transcriptional Axis in the Hippocampus of Learned Helplessness Rats.

Impaired synaptic plasticity has been linked to dynamic gene regulatory network changes. Recently, gene regulation has been introduced with the emerging concept of unique N6-methyladenosine (m6A)-based reversible transcript methylation. In this study, we tested whether m6A RNA methylation may potentially serve as a link between the stressful insults and altered expression of plasticity-related genes. Expression of plasticity genes Nr3c1, Creb1, Ntrk2; m6A-modifying enzymes Fto, methyltransferase like (Mettl)-3 and 14; DNA methylation enzymes Dnmt1, Dnmt3a; transcription factor C/ebp-α; and miRNA-124-3p were determined by quantitative polymerase chain reaction (qPCR) in the hippocampus of rats that showed susceptibility to develop stress-induced depression (learned helplessness). M6A methylation of plasticity-related genes was determined following m6A mRNA immunoprecipitation. Chromatin immunoprecipitation was used to examine the endogenous binding of C/EBP-α to the Fto promoter. MiR-124-mediated post-transcriptional inhibition of Fto via C/EBPα was determined using an in vitro model. Hippocampus of learned helplessness rats showed downregulation of Nr3c1, Creb1, and Ntrk2 along with enrichment in their m6A methylation. A downregulation in demethylating enzyme Fto and upregulation in methylating enzyme Mettl3 were also noted. The Fto promoter was hypomethylated due to the lower expression of Dnmt1 and Dnmt3a. At the same time, there was a lower occupancy of transcription factor C/EBPα on the Fto promoter. Conversely, C/ebp-α transcript was downregulated via induced miR-124-3p expression. Our study mechanistically linked defective C/EBP-α-FTO-axis, epigenetically influenced by induced expression of miR-124-3p, in modifying m6A enrichment in plasticity-related genes. This could potentially be linked with abnormal neuronal plasticity in depression.

High‐Performance Memristor Based on 2D Layered BiOI Nanosheet for Low‐Power Artificial Optoelectronic Synapses

AbstractArtificial optoelectronic synapses with both electrical and light‐induced synaptic behaviors have recently been studied for applications in neuromorphic computing and artificial vision systems. However, the combination of visual perception and high‐performance information processing capabilities still faces challenges. In this work, the authors demonstrate a memristor based on 2D bismuth oxyiodide (BiOI) nanosheets that can exhibit bipolar resistive switching (RS) performance as well as electrical and light‐induced synaptic plasticity eminently suitable for low‐power optoelectronic synapses. The fabricated memristor exhibits high‐performance RS behaviors with a high ON/OFF ratio up to 105, an ultralow SET voltage of ≈0.05 V which is one order of magnitude lower than that of most reported memristors based on 2D materials, and low power consumption. Furthermore, the memristor demonstrates not only electrical voltage‐driven long‐term potentiation, depression plasticity, and paired‐pulse facilitation, but also light‐induced short‐ and long‐term plasticity. Moreover, the photonic synapse can be used to simulate the “learning experience” behaviors of human brain. Consequently, not only the memristor based on BiOI nanosheets shows ultra‐low SET voltage and low‐power consumption, but also the optoelectronic synapse provides new material and strategy to construct low‐power retina‐like vision sensors with functions of perceiving and processing information.

Synaptic Microenvironment in Depressive Disorder: Insights from Synaptic Plasticity.

Depression is a major disease that can affect both mental and physical health, limits psychosocial functioning and diminishes the quality of life. But its complex pathogenesis remains poorly understood. The dynamic changes of synaptic structure and function, known as synaptic plasticity, occur with the changes of different cellular microenvironment and are closely related to learning and memory function. Accumulating evidence implies that synaptic plasticity is integrally involved in the pathological changes of mood disorders, especially in depressive disorder. However, the complex dynamic process of synaptic plasticity is influenced by many factors. Here, we reviewed and discussed various factors affecting synaptic plasticity in depression, and proposed a specific framework named synaptic microenvironment, which may be critical for synaptic plasticity under pathological conditions. Based on this concept, we will show how we understand the balance between the synaptic microenvironment and the synaptic plasticity network in depression. Finally, we point out the clinical significance of the synaptic microenvironment in depression.

Changes in Hippocampal Plasticity in Depression and Therapeutic Approaches Influencing These Changes.

Depression is a common neurological disease that seriously affects human health. There are many hypotheses about the pathogenesis of depression, and the most widely recognized and applied is the monoamine hypothesis. However, no hypothesis can fully explain the pathogenesis of depression. At present, the brain-derived neurotrophic factor (BDNF) and neurogenesis hypotheses have highlighted the important role of plasticity in depression. The plasticity of neurons and glial cells plays a vital role in the transmission and integration of signals in the central nervous system. Plasticity is the adaptive change in the nervous system in response to changes in external signals. The hippocampus is an important anatomical area associated with depression. Studies have shown that some antidepressants can treat depression by changing the plasticity of the hippocampus. Furthermore, caloric restriction has also been shown to affect antidepressant and hippocampal plasticity changes. In this review, we summarize the latest research, focusing on changes in the plasticity of hippocampal neurons and glial cells in depression and the role of BDNF in the changes in hippocampal plasticity in depression, as well as caloric restriction and mitochondrial plasticity. This review may contribute to the development of antidepressant drugs and elucidating the mechanism of depression.

Ketamine improves short-term plasticity in depression by enhancing sensitivity to prediction errors

Major depressive disorder negatively impacts the sensitivity and adaptability of the brain's predictive coding framework. The current electroencephalography study into the antidepressant properties of ketamine investigated the downstream effects of ketamine on predictive coding and short-term plasticity in thirty patients with depression using the auditory roving mismatch negativity (rMMN). The rMMN paradigm was run 3–4 h after a single 0.44 mg/kg intravenous dose of ketamine or active placebo (remifentanil infused to a target plasma concentration of 1.7 ng/mL) in order to measure the neural effects of ketamine in the period when an improvement in depressive symptoms emerges. Depression symptomatology was measured using the Montgomery-Asberg Depression Rating Scale (MADRS); 70% of patients demonstrated at least a 50% reduction their MADRS global score. Ketamine significantly increased the MMN and P3a event related potentials, directly contrasting literature demonstrating ketamine's acute attenuation of the MMN. This effect was only reliable when all repetitions of the post-deviant tone were used. Dynamic causal modelling showed greater modulation of forward connectivity in response to a deviant tone between right primary auditory cortex and right inferior temporal cortex, which significantly correlated with antidepressant response to ketamine at 24 h. This is consistent with the hypothesis that ketamine increases sensitivity to unexpected sensory input and restores deficits in sensitivity to prediction error that are hypothesised to underlie depression. However, the lack of repetition suppression evident in the MMN evoked data compared to studies of healthy adults suggests that, at least within the short term, ketamine does not improve deficits in adaptive internal model calibration.

The Role of BDNF on Neural Plasticity in Depression.

Using behavioral, pharmacological, and molecular methods, lots of studies reveal that depression is closely related to the abnormal neural plasticity processes occurring in the prefrontal cortex and limbic system such as the hippocampus and amygdala. Meanwhile, functions of the brain-derived neurotrophic factor (BDNF) and the other neurotrophins in the pathogenesis of depression are well known. The maladaptive neuroplastic in depression may be related to alterations in the levels of neurotrophic factors, which play a central role in plasticity. Enhancement of neurotrophic factors signaling has great potential in therapy for depression. This review highlights the relevance of neurotrophic factors mediated neural plasticity and pathophysiology of depression. These studies reviewed here may suggest new possible targets for antidepressant drugs such as neurotrophins, their receptors, and relevant signaling pathways, and agents facilitating the activation of gene expression and increasing the transcription of neurotrophic factors in the brain.

Perturbation of Ephrin Receptor Signaling and Glutamatergic Transmission in the Hypothalamus in Depression Using Proteomics Integrated With Metabolomics

Hypothalamic dysfunction is a key pathological factor in inflammation-associated depression. In the present study, isobaric tags for relative-absolute quantitation (iTRAQ) combined with mass spectrometry and gas chromatography-mass spectrometry (GC-MS) were employed to detect the proteomes and metabolomes in the hypothalamus of the lipopolysaccharide (LPS)-induced depression mouse, respectively. A total of 187 proteins and 27 metabolites were differentially expressed compared with the control group. Following the integration of bi-omics data, pertinent pathways and molecular interaction networks were further identified. The results indicated altered molecules were clustered into Ephrin receptor signaling, glutamatergic transmission, and inflammation-related signaling included the LXR/RXR activation, FXR/RXR activation, and acute phase response signaling. First discovered in the hypothalamus, Ephrin receptor signaling regulates N-methyl-D-aspartate receptor (NMDAR)-predominant glutamatergic transmission, and further acted on AKT signaling that contributed to changes in hypothalamic neuroplasticity. Ephrin type-B receptor 2 (EPHB2), a transmembrane receptor protein in Ephrin receptor signaling, was significantly elevated and interacted with the accumulated NMDAR subunit GluN2A in the hypothalamus. Additionally, molecules involved in synaptic plasticity regulation, such as hypothalamic postsynaptic density protein-95 (PSD-95), p-AKT and brain-derived neurotrophic factor (BDNF), were significantly altered in the LPS-induced depressed group. It might be an underlying pathogenesis that the EPHB2-GluN2A-AKT cascade regulates synaptic plasticity in depression. EPHB2 can be a potential therapeutic target in the correction of glutamatergic transmission dysfunction. In summary, our findings point to the previously undiscovered molecular underpinnings of the pathophysiology in the hypothalamus of inflammation-associated depression and offer potential targets to develop antidepressants.

Ketamine Treatment Effects on Synaptic Plasticity in Depression

Ketamine Treatment Effects on Synaptic Plasticity in Depression

Ratio of plasma BDNF to leptin levels are associated with treatment response in major depressive disorder but not in panic disorder: A 12-week follow-up study

BackgroundA link between brain-derived neurotrophic factor (BDNF) expression and the mood regulatory effect of leptin has been suggested in the pathophysiology of major depressive disorder (MDD). We investigated treatment response and pre-treatment leptin and BDNF in patients with MDD and with panic disorder (PD). MethodsWe recruited 41 patients with MDD, 52 patients with PD, and 59 matched healthy controls. All subjects completed five visits (at baseline, 2, 4, 8, and 12 weeks), and both MDD and PD patients were treated with standard pharmacotherapy for 12 weeks. Plasma BDNF (pBDNF) and blood leptin levels were obtained along with a 17-item Hamilton Depression Scale rating (HDRS-17) score at every visit. ResultsThe ratio of pre-treatment pBDNF to leptin was significantly lower in patients with MDD and PD compared to healthy controls (p = 0.024), but was not associated with severity of depressive or anxiety symptoms. Pre-treatment pBDNF:leptin ratio was significantly higher in treatment responders than in non-responders (p = 0.012) in MDD but not in PD. This difference was larger in MDD patients with appetite loss (p = 0.034). In multivariate analysis, pre-treatment pBDNF:leptin ratio was significantly associated with treatment responsiveness (Adjusted Odds Ration [AOR] = 2.50, 95% CI 1.02–6.14) in MDD. Limitationsmall sample size; limited information on detailed pharmacological effects. ConclusionsA relatively higher ratio of pre-treatment pBDNF to leptin was associated with greater treatment response in MDD but not in PD. Further research should focus on exploration of a link between BDNF and leptin underlying neuronal plasticity in depression.

ITRAQ-Based Protein Profiling in CUMS Rats Provides Insights into Hippocampal Ribosome Lesion and Ras Protein Changes Underlying Synaptic Plasticity in Depression.

Hippocampal atrophy is one of the key changes in the brain implicated in the biology of depression. However, the precise molecular mechanism remains poorly understood due to a lack of biomarkers. In this research, we used behavioral experiments to evaluate anxiety and anhedonia levels in depressed rats using chronic unpredictable mild stress (CUMS) modeling. We also used isobaric tag for relative and absolute quantitation (iTRAQ) to identify the differentially expressed hippocampal proteins between depressed and normal rats. Bioinformatics analyses were also performed for a better understanding. The results showed that CUMS rats had higher anxiety and anhedonia levels than control rats, along with hippocampal lesions. Through iTRAQ and bioinformatics analyses, we found that ribosome proteins were significantly downregulated and Ras proteins exhibited a mixed change in the hippocampus of depressed rats. These findings suggest that the expression of hippocampal ribosome lesions and Ras proteins is significantly different in depressed rats than in control rats, providing new insights into the neurobiology of depression.

Synthesis of Donor–Acceptor Gridarenes with Tunable Electronic Structures for Synaptic Learning Memristor

A series of donor–acceptor “”-shaped gridarenes were synthesized with BT units as the crossbeam and thiophene units as the π-bridge. The donor–acceptor gridization functional effects on optoelectronic properties were then studied experimentally and computationally to provide a platform to adjust the energetics of the highest occupied molecular orbital/lowest unoccupied molecular orbital levels. Finally, G-DTh-based two-terminal memristor indium tin oxide/G-DTh:TBAPF6/Al successfully realizes conventional learning processes, synaptic potentiation, and depression plasticity which are essential for neuromorphic computation.

Quantitative Proteomic Analysis Reveals Synaptic Dysfunction in the Amygdala of Rats Susceptible to Chronic Mild Stress

The amygdala plays a key role in the pathophysiology of depression, but the molecular mechanisms underlying amygdalar hyperactivity in depression remain unclear. In this study, we used a chronic mild stress (CMS) protocol to separate susceptible and insusceptible rat subgroups. Proteomes in the amygdalae were analyzed differentially across subgroups based on labeling with isobaric tags for relative and absolute quantitation (iTRAQ) combined with mass spectrometry. Of 2562 quantified proteins, 102 were differentially expressed. Several proteins that might be associated with the stress insusceptibility/susceptibility difference, including synapse-related proteins, were identified in the amygdala. Immunoblot analysis identified changes in VGluT1, NMDA GluN2A and GluN2B and AMPA GluA1 receptors, and PSD-95, suggesting that CMS perturbs glutamatergic transmission in the amygdala. Changes in these regulatory and structural proteins provide insight into the molecular mechanisms underlying the abnormal synaptic morphological and functional plasticity in the amygdalae of stress-susceptible rats. Interestingly, the expression level of CaMKIIβ, potentially involved in regulation of glutamatergic transmission, was significantly increased in the susceptible group. Subsequent in vitro experimentation showed that overexpression of CaMKIIβ increased the expression of PSD-95 and GluA1 in cultured hippocampal neurons. This result suggested that CaMKIIβ functions upstream from PSD-95 and GluA1 to affect LTP-based postsynaptic functional plasticity in the amygdalae of susceptible rats. Therefore, amygdalar CaMKIIβ is a potential antidepressant target. Collectively, our findings contribute to a better understanding of amygdalar synaptic plasticity in depression.

Cortical Plasticity in Depression.

Neural plasticity is considered the neurophysiological correlate of learning and memory, although several studies have also noted that it plays crucial roles in a number of neurological and psychiatric diseases. Indeed, impaired brain plasticity may be one of the pathophysiological mechanisms that underlies both cognitive decline and major depression. Moreover, a degree of cognitive impairment is frequently observed throughout the clinical spectrum of mood disorders, and the relationship between depression and cognition is often bidirectional. However, most evidence for dysfunctional neural plasticity in depression has been indirect. Transcranial magnetic stimulation has emerged as a noninvasive tool for investigating several parameters of cortical excitability with the aim of exploring the functions of different neurotransmission pathways and for probing in vivo plasticity in both healthy humans and those with pathological conditions. In particular, depressed patients exhibit a significant interhemispheric difference in motor cortex excitability, an imbalanced inhibitory or excitatory intracortical neurochemical circuitry, reduced postexercise facilitation, and an impaired long-term potentiation-like response to paired-associative transcranial magnetic stimulation, and these symptoms may indicate disrupted plasticity. Research aimed at disentangling the mechanism by which neuroplasticity plays a role in the pathological processes that lead to depression and evaluating the effects of modulating neuroplasticity are needed for the field to facilitate more powerful translational research studies and identify novel therapeutic targets.

The Role of Neural Plasticity in Depression: From Hippocampus to Prefrontal Cortex.

Neural plasticity, a fundamental mechanism of neuronal adaptation, is disrupted in depression. The changes in neural plasticity induced by stress and other negative stimuli play a significant role in the onset and development of depression. Antidepressant treatments have also been found to exert their antidepressant effects through regulatory effects on neural plasticity. However, the detailed mechanisms of neural plasticity in depression still remain unclear. Therefore, in this review, we summarize the recent literature to elaborate the possible mechanistic role of neural plasticity in depression. Taken together, these findings may pave the way for future progress in neural plasticity studies.