ß-asarone inhibits autophagy by activating the PI3K/Akt/mTOR pathway in a rat model of depression in Parkinson's disease.

OBJECTIVE: It is unclear whether ß-asarone has a good antidepressant effect and what is the main mechanism in Depression in Parkinson's disease (DPD) model rats. METHODS: In this study, DPD model rats were screened from 6-OHDA induced rats by sucrose preference test (SPT) and forced swimming test (FST). DPD model rats were divided into eight groups: model group, pramipexole group, ß-asarone low-dose group (ß-asarone 7.5 group), ß-asarone medium-dose group (ß-asarone 15 group), ß-asarone high-dose group (ß-asarone 30 group), 3-MA group, rapamycin group, and PI3K inhibitor group. 28 days after the end of treatment, open field test (OFT), SPT and FST were conducted in rats. The level of α-synuclein (α-syn) in the striatum was determined by enzyme-linked immunosorbent assay (ELISA). The expression of Beclin-1, p62 in the striatum was determined by western blot. The expression of PI3K, p-PI3K, Akt, p-Akt, mTOR, p-mTOR, Beclin-1, and p62 in the hippocampus was determined by western blot. The spine density of neurons in the hippocampus was detected by golgi staining. RESULTS: The results showed that 4-week oral administration of ß-asarone improve the motor and depressive symptoms of DPD model rats, and decrease the content of α-syn in the striatum. ß-asarone inhibited the expression of autophagy in the striatum of DPD model rats. Furthermore, ß-asarone decreased the levels of Beclin-1 protein, increased the expression of p62, p-PI3K, p-AKT, and p-mTOR, and improved the density of neuron dendritic spine in the hippocampus. CONCLUSIONS: We concluded that ß-asarone might improve the behavior of DPD model rats by activating the PI3K/Akt/mTOR pathway, inhibiting autophagy and protecting neuron.

Behind the Mask: Parkinson's Disease and Depression.

Parkinson's disease (PD) is a common, prevalent neurodegenerative disease. It is mainly characterized by motor symptoms such as rigidity, tremors, and bradykinesia, but it can also manifest with non-motor symptoms, of which depression is the most frequent. The latter can impair the quality of life, yet it gets overlooked and goes untreated because of the significant overlap in their clinical features, hence making the diagnosis difficult. Furthermore, there is limited data on the availability of appropriate criteria for making the diagnosis of depression in PD patients, as it can occur with varying expressions throughout the course of PD or it can also precede it. This review article has included a brief discussion on the diagnosis of depression in PD patients and their overlapped clinical manifestations. Understanding the mechanisms underlying the disease processes of PD and depression and the pathways interconnecting them gives better knowledge on devising treatment options for the patients. Only studies from Pubmed were included and all other databases were excluded. Studies from the last 50 years were included. Suitable references included in these studies were also extracted. Thus, depression in PD and PD in depression, along with their pharmacological and non-pharmacological treatment options, have been discussed.

Acupuncture inhibits autophagy and repairs synapses by activating the mTOR pathway in Parkinson's disease depression model rats.

Acupuncture is a good treatment for depression in Parkinson's disease (DPD), so the possible mechanism of acupuncture in the treatment of DPD was explored in this study. Firstly, observing the behavioral changes of the DPD rat model, the regulation of monoamine neurotransmitters dopamine (DA) and 5-hydroxytryptamine (5-HT) in the midbrain, the change of α-synuclein (α-syn) in the striatum, the efficacy of acupuncture in the treatment of DPD was discussed. Secondly, autophagy inhibitors and activators were selected to judge the effect of acupuncture on autophagy in the DPD rat model. Finally, an mTOR inhibitor was used to observe the effect of acupuncture on the mTOR pathway in the DPD rat model. The results showed that acupuncture could improve the motor and depressive symptoms of DPD model rats, increase the content of DA and 5-HT, and decrease the content of ɑ-syn in the striatum. Acupuncture inhibited the expression of autophagy in the striatum of DPD model rats. At the same time, acupuncture upregulates p-mTOR expression, inhibits autophagy, and promotes synaptic protein expression. Therefore, we concluded that acupuncture might improve the behavior of DPD model rats by activating the mTOR pathway, inhibiting autophagy from removing α-syn and repairing synapses.

Depression in Parkinson's Disease: A Narrative Review.

Parkinson's disease (PD) is a progressive neurodegenerative age-related disorder that affects the central nervous system (CNS) and is characterized by uncontrollable movements such as shaking, stiffness, and loss of balance and coordination. Depression is a common non-motor manifestation of PD, but unfortunately, depression remains unrecognized and often undertreated. The underlying pathophysiology of depression in PD is complicated, and many studies have been conducted to know the exact cause, but the question remains unanswered. In this article, we discuss various pathophysiologies by which depression occurs in PD. The most widely accepted theories are neuroinflammation and monoamine oxidase theory. This article also explored the pharmacological treatment of depression in PD; this involves standard antidepressant therapy such as tricyclic antidepressants (TCA), serotonin-norepinephrine reuptake inhibitors (SNRI), selective serotonin reuptake inhibitors (SSRI), and monoamine oxidase inhibitors (MAO); non-pharmacological treatments such as electroconvulsive therapy (ECT), cognitive-behavioral therapy (CBT) have also been discussed. However, physicians hesitate to prescribe antidepressants to patients with PD due to concerns about harmful drug-drug interactions between antidepressants and antiparkinsonian drugs. Despite the complicated link between PD and depression, the co-administration of antidepressants and antiparkinsonian drugs is safe and beneficial when appropriately managed. However, early recognition and initiation of treatment of depression in PD reduces the longitudinal course and improves the cross-sectional picture. This review article also explored the clinical and diagnostic findings and impact on the quality of life of depression in PD.

The altered multiscale dynamics of spontaneous brain activity in depression with Parkinson's disease.

BACKGROUND: Depression is one typical mood disorder in Parkinson's disease (DPD). The alterations in the resting-state brain activities are believed to be associated with DPD. These resting-state activities are regulated by neurophysiological components over multiple temporal scales. The multiscale dynamics of these spontaneous fluctuations are thus complex, but not well-characterized. OBJECTIVE: To characterize the complexity of the spontaneous blood-oxygen-level-dependent (BOLD) of fMRI in DPD. We hypothesized that (1) compared to non-depression PD (NDPD), the complexity in DPD would be lower; and (2) the diminished complexity would be associated with lower connections/communications between brain regions. METHODS: Twenty-nine participants (10 in DPD and 19 in NDPD) who were naïve to medications completed a resting-sate functional MRI scan. The BOLD complexity within each voxel was calculated by using multiscale entropy (MSE). The complexity of the whole brain and each of the 90 regions parcellated following automated-anatomical-labeling template was then obtained by averaging voxel-wised complexity across all brain regions or within each region. The level of connections of regions with diminished complexity was measured by their own global functional connectivity (FC). RESULTS: As compared to NDPD patients, the whole-brain complexity and complexity in 18 regions were significantly lower in DPD (F > 16.3, p < 0.0005). Particularly, in eight of the 18 regions, lower complexity was associated with lower global FC (Beta = 0.333 ~ 0.611, p = 0.000 ~ 0.030). CONCLUSION: The results from this pilot study suggest that the resting-state BOLD complexity may provide critical knowledge into the pathology of DPD. Future studies are thus warranted to confirm the findings of this study.

Similarities Between Depression and Neurodegenerative Diseases: Pathophysiology, Challenges in Diagnosis and Treatment Options.

Depressive disorder and neurodegenerative diseases are two different clinical entities. Depression is a common psychiatric disorder in the general population. However, when present concomitantly with neurodegenerative disorders, its diagnosis becomes challenging. In many cases, patients remain undiagnosed and hence, untreated, worsening the prognosis of the neurodegenerative diseases and impairing the quality of life. One of the possible reasons for the difficulties in diagnosis in such cases is that both conditions affect the central nervous system, so there might be an overlap of symptoms leading to a missed diagnosis of depression in a neurodegenerative disease patient and vice versa. Symptoms such as irritability, apathy, and decreased cognition are common to both types of disorders. Some neurodegenerative diseases, especially Alzheimer's disease, can initially present as a depressive prodrome. This may cause a difficulty in differentiating between these two conditions and a diagnosis of either conditions may be missed; hence an opportunity for timely intervention and improved outcomes is missed. An approach towards analyzing and comparing the pathological mechanisms common to both disease types will create a better understanding of depression and neurodegenerative diseases, identify their similarities, and develop improved clinical criteria to help clinicians make a timely diagnosis of these conditions present together. In the present review, various studies related to common pathological links, concomitant diagnosis challenges, and ongoing research about different treatment options are discussed.

Development of a depression in Parkinson's disease prediction model using machine learning.

BACKGROUND: It is important to diagnose depression in Parkinson's disease (DPD) as soon as possible and identify the predictors of depression to improve quality of life in Parkinson's disease (PD) patients. AIM: To develop a model for predicting DPD based on the support vector machine, while considering sociodemographic factors, health habits, Parkinson's symptoms, sleep behavior disorders, and neuropsychiatric indicators as predictors and provide baseline data for identifying DPD. METHODS: This study analyzed 223 of 335 patients who were 60 years or older with PD. Depression was measured using the 30 items of the Geriatric Depression Scale, and the explanatory variables included PD-related motor signs, rapid eye movement sleep behavior disorders, and neuropsychological tests. The support vector machine was used to develop a DPD prediction model. RESULTS: When the effects of PD motor symptoms were compared using "functional weight", late motor complications (occurrence of levodopa-induced dyskinesia) were the most influential risk factors for Parkinson's symptoms. CONCLUSION: It is necessary to develop customized screening tests that can detect DPD in the early stage and continuously monitor high-risk groups based on the factors related to DPD derived from this predictive model in order to maintain the emotional health of PD patients.

The role of inflammatory cytokines in patients with depression in Parkinson's disease / 实用医学杂志

Objective To compare the serum levels of interleukin(IL)-6,IL-18 and tumor necrosis factor alpha(TNF-α)in patients with DPD,PD,depression disorder and healthy controls and to analyze the correlations of serum inflammatory factors in DPD patients. Methods Serum levels of IL-6,IL-18 and TNF-αwere measured using enzyme linked immunosorbent assay(ELISA) kits. Several scales were performedin DPD patients. Results DPD,PD and depression disorder patients had significant lower baseline levels of IL-6 and TNF-αwhen compared to healthy controls(P < 0.05). The levels of IL-6 and TNF-α in DPD patients were significantly increased after 4 weeks of anti-depression treatment(P < 0.05). No difference of cytokines levels in gender and in severity of DPD patients was detected Serum levels of these inflammatory cytokines were not significantly correlated with the UP-DRS Ⅲ,H & Y,MMSE and HAMD scores in DPD patients. Conclusions Serum inflammatory factors(IL-6, TNF-α)were altered in patients with DPD in the earlier course of disease. However ,the role of IL-18 remained unknownin the occurrence of DPD disease.

The role of inflammatory cytokines in patients with depression in Parkinson's disease / 实用医学杂志

Objective To compare the serum levels of interleukin(IL)-6,IL-18 and tumor necrosis factor alpha(TNF-α)in patients with DPD,PD,depression disorder and healthy controls and to analyze the correlations of serum inflammatory factors in DPD patients. Methods Serum levels of IL-6,IL-18 and TNF-αwere measured using enzyme linked immunosorbent assay(ELISA) kits. Several scales were performedin DPD patients. Results DPD,PD and depression disorder patients had significant lower baseline levels of IL-6 and TNF-αwhen compared to healthy controls(P < 0.05). The levels of IL-6 and TNF-α in DPD patients were significantly increased after 4 weeks of anti-depression treatment(P < 0.05). No difference of cytokines levels in gender and in severity of DPD patients was detected Serum levels of these inflammatory cytokines were not significantly correlated with the UP-DRS Ⅲ,H & Y,MMSE and HAMD scores in DPD patients. Conclusions Serum inflammatory factors(IL-6, TNF-α)were altered in patients with DPD in the earlier course of disease. However ,the role of IL-18 remained unknownin the occurrence of DPD disease.