Vascular risk factors and depression in Parkinson's disease

Ou, Ruwei; Wei, Qianqian; Hou, Yanbing; Yuan, Xianglei; Song, Wei; Cao, Bei; Liu, H.; Zhang, L.; Chen, Y.; Shang, Huifang

doi:10.1111/ene.13551

Cited by 12 publications

(6 citation statements)

References 36 publications

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“…Depression is one of the most common psychiatric symptoms, and it has been demonstrated to occur prior to the onset of motor symptoms of PD (Ou et al, 2017 ). According to the natural phenomenon that mice prefer a sweetened solution rather than water, whereas depressed mice will no longer exhibit that preference, we performed SPT to assess an anhedonic state of animals (Branchi et al, 2008 ).…”

Section: Discussionmentioning

confidence: 99%

Investigation of Behavioral Dysfunctions Induced by Monoamine Depletions in a Mouse Model of Parkinson's Disease

Jiao

et al. 2018

Front. Cell. Neurosci.

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Parkinson's disease (PD) is characterized not only by typical motor symptoms, but also by nonmotor symptoms in the early stages. In addition to the loss of dopaminergic (DAergic) neurons, progressive degenerations of noradrenergic (NA) and serotonergic (5-HT) neurons were also observed. However, the respective effects and interactions of these monoamine depletions on certain nonmotor symptoms are still largely unknown. In the present study, we performed selective depletions of NA, 5-HT and DA in mice by intraperitioneal injection of N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine hydrochloride (DSP-4), 4-chloro-L-phenylalanine (pCPA) and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), respectively. DSP-4 led to a 34% decrease in the number of NAergic neurons in the locus coeruleus, and MPTP led to a 30% decrease in the number of DAergic neurons in the substantia nigra. Although there was no obvious change in the number of 5-HTergic neurons in the dorsal raphe nucleus after pCPA treatment, the levels of 5-HT and its metabolite in the frontal cortex and hippocampus were reduced, respectively. Locomotor activity deficit was induced by DA depletion and a decrease in traveled distance was potentiated by additional NA depletion. Despair-associated depressive-like behavior could be observed in every group. Anxiety states emerged only from the combined depletion of two or three monoamines. However, combined depletion of the three monoamines dramatically induced anhedonia, and it could also aggravate the depressive-like and anxiety behavior. Furthermore, NA depletion significantly reduced spatial learning and memory ability, which was not enhanced by additional 5-HT or DA depletion. Our data highlighted the interactive role of NA, 5-HT and DA in the motor, emotional and cognitive deficits, providing new insight into the complex orchestration of impaired monoaminergic systems that related to the pathology of PD.

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Section: Discussionmentioning

confidence: 99%

Investigation of Behavioral Dysfunctions Induced by Monoamine Depletions in a Mouse Model of Parkinson's Disease

Jiao

et al. 2018

Front. Cell. Neurosci.

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“…From the aspect of symptoms, worse motor symptoms might be associated with PD-D (7). However, there were few studies that investigated the relationship between clinical type of PD and PD-D. For non-motor symptoms, most studies agreed that anxiety was the independent influencing factor (8), but other non-motor symptoms, for instance, fatigue, cognitive decline and sleep disturbances, had considerably varied reports (4, 9). Therefore, there is a lack of consensus on the influencing factors of PD-D. Studies consisting of large samples are necessary to explore both general and specific factors related to PD-D.…”

Section: Introductionmentioning

confidence: 99%

An Investigation on the Clinical Features and Neurochemical Changes in Parkinson's Disease With Depression

et al. 2019

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Objective: To investigate the clinical features and neurochemical changes in Parkinson's disease with depression (PD-D).Methods: A total of 478 PD patients were divided into PD-D and PD patients without depression (PD-ND) groups according to the 24-item Hamilton Depression Rating Scale (HAMD) score. Demographic variables, motor and non-motor symptoms and activities of daily living were evaluated. The independent influencing factors of PD-D were investigated via binary logistic regression analysis. The levels of neurotransmitters in cerebrospinal fluid (CSF) were measured and their correlations with HAMD score were analyzed.Results: The proportion of PD-D was 59.0%, of which 76.95, 20.92, and 2.13% had mild, moderate, and severe depression, respectively. Anxiety/somatization was the most prevalent sub-factor of HAMD in PD-D. The scores of UPDRS III, postural instability/gait difficulty (PIGD) type and the scores of 14-item Hamilton Anxiety Scale (HAMA) and 14-item Chalder Fatigue Scale (FS) were independently associated with PD-D. The levels of dopamine (DA) and 5-hydroxytryptamine (5-HT) were all significantly reduced in PD-D group compared with those in PD-ND group. HAMD scores were negatively correlated with the DA levels in CSF.Conclusions: PD patients have a high proportion of depression, mainly of mild and moderate levels. The profile of depression in PD population is subtly different from that of the general population. Motor symptoms, PIGD type, anxiety and fatigue are the significant influencing factors of PD-D. Compared to 5-HT, DA may play a more important role in PD-D.

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“…Depression usually precedes the onset of motor symptoms in PD [24]. The exact mechanism of PD associated with depression is not yet fully understood.…”

Section: Discussionmentioning

confidence: 99%

D1R-PKA signaling activation in PFC mediated by GDNF facilitates depression remission in Parkinson's disease

Liu

Zhou

Xue

et al. 2023

Preprint

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Depression is one of the most common non-motor symptoms of Parkinson's disease (PD), which can cause a severe decline in the quality of life of PD patients. Dopamine receptors (DRs) expressed in glutamatergic pyramidal cells in the medial prefrontal cortex (mPFC) shape the local field activity, contributing to behavioral and mood disorders regulation. Studies have demonstrated that the Glial cell-derived neurotrophic factor (GDNF) has a potential antidepressant effect. However, PD has yet to report the anti-depression consequences of GDNF positioning injection into mPFC on DRs. Here, we reported exogenous GDNF injection to mPFC, resulting in up-regulation of D1 dopamine receptor (D1R) protein levels, and found that activating the PKA pathway mediated by D1R produces a long-lasting antidepressant response. In contrast, D2R expression under GDNF stimulation was constant, which indicated D2R signal was ineffective across depression-like measures. Furthermore, we used Golgi staining and western blot to display enhanced synaptic plasticity, such as the increased dendritic branches and dendritic spines, after GDNF treatment in PD models. Therefore, our results identify an exogenous GDNF positive effect on synaptic plasticity mediated by D1R signaling in mPFC to facilitate depression remission in PD.

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Vascular risk factors and depression in Parkinson's disease

Abstract: Our study failed to verify the vascular depression hypothesis in PD. On the contrary, it was demonstrated that overweight/obesity is negatively associated with the presence of depression in PD.

Cited by 12 publications

References 36 publications

Investigation of Behavioral Dysfunctions Induced by Monoamine Depletions in a Mouse Model of Parkinson's Disease

Investigation of Behavioral Dysfunctions Induced by Monoamine Depletions in a Mouse Model of Parkinson's Disease

An Investigation on the Clinical Features and Neurochemical Changes in Parkinson's Disease With Depression

D1R-PKA signaling activation in PFC mediated by GDNF facilitates depression remission in Parkinson's disease

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