Prodromal non-motor symptoms of Parkinson's disease

Pellicano, Clelia; Benincasa, Dario; Pisani, Vincenzo; Buttarelli, Francesca Romana; Giovannelli, Morena; Pontieri, Francesco E.

doi:10.2147/nedt.2007.3.1.145

Cited by 85 publications

(44 citation statements)

References 76 publications

(76 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In order to rule out potential sensory deficits as a cause of altered rotarod behavior, we tested mice for olfactory function because one common preclinical symptom of PD is anosmia (Doty et al, 1988, Doty et al, 1992, Pellicano et al, 2007). We hypothesized that decreased olfactory function may cause Parkin −/− DJ-1 −/− mice to explore less and consequently show longer latencies to fall off of the rotarod.…”

Section: Resultsmentioning

confidence: 99%

Surprising behavioral and neurochemical enhancements in mice with combined mutations linked to Parkinson's disease

Hennis¹,

Marvin²,

Taylor³

et al. 2014

Neurobiology of Disease

View full text Add to dashboard Cite

Parkinson's disease (PD) is the second most common neurodegenerative disorder behind Alzheimer's disease. There are currently no therapies proven to halt or slow the progressive neuronal cell loss in PD. A better understanding of the molecular and cellular causes of PD is needed to develop disease-modifying therapies. PD is an age-dependent disease that causes the progressive death of dopamine-producing neurons in the brain. Loss of substantia nigra dopaminergic neurons results in locomotor symptoms such as slowness of movement, tremor, rigidity and postural instability. Abnormalities in other neurotransmitters, such as serotonin, may also be involved in both the motor and non-motor symptoms of PD. Most cases of PD are sporadic but many families show a Mendelian pattern of inherited parkinsonism and causative mutations have been identified in genes such as Parkin, DJ-1, PINK1, alpha-synuclein and Leucine Rich Repeat Kinase 2 (LRRK2). Although the definitive causes of idiopathic PD remain uncertain, the activity of the antioxidant enzyme glutathione peroxidase 1 (Gpx1) is reduced in PD brains and has been shown to be a key determinant of vulnerability to dopaminergic neuron loss in PD animal models. Furthermore, Gpx1 activity decreases with age in human substantia nigra but not rodent substantia nigra. Therefore, we crossed mice deficient for both Parkin and DJ-1 with mice deficient for Gpx1 to test the hypothesis that loss-of-function mutations in Parkin and DJ-1 cause PD by increasing vulnerability to Gpx1 deficiency. Surprisingly, mice lacking Parkin, DJ-1 and Gpx1 have increased striatal dopamine levels in the absence of nigral cell loss compared to wild-type, Gpx1−/−, and Parkin−/−DJ-1−/− mutant mice. Additionally, Parkin−/−DJ-1−/− mice exhibit improved rotarod performance and have increased serotonin in the striatum and hippocampus. Stereological analysis indicated that the increased serotonin levels were not due to increased serotonergic projections. The results of our behavioral, neurochemical and immunohistochemical analyses reveal that PD-linked mutations in Parkin and DJ-1 cause dysregulation of neurotransmitter systems beyond the nigrostriatal dopaminergic circuit and that loss-of-function mutations in Parkin and DJ-1 lead to adaptive changes in dopamine and serotonin especially in the context of Gpx1 deficiency.

show abstract

Section: Resultsmentioning

confidence: 99%

Surprising behavioral and neurochemical enhancements in mice with combined mutations linked to Parkinson's disease

Hennis¹,

Marvin²,

Taylor³

et al. 2014

Neurobiology of Disease

View full text Add to dashboard Cite

show abstract

“…The etiology and pathogensis of PD still remains unclear, but it is thought that it may be caused by a combination of genetic and environmental factors (Braak et al 2004, Schapira 2007, Mosharov et al 2009, Brichta and Greengard 2014, Yadav and Li 2015, Goedert 2015. It is well documented that the cardinal features of PD motor symptoms including bradykinesia, muscular rigidity, rest tremor, and postural and gait instability can be entirely explained by degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNpc) (Cenci 2007, Pellicano et al 2007, Fahn 2008, Brichta and Greengard 2014, Yadav and Li 2015. Consequently, treatment for PD has classically involved supplementation of endogenous dopamine (DA) with medicinal options that either replace dopamine or augment the nigrostriatal dopaminergic pathway (Schapira 2007, Fahn 2008, Yadav and Li 2015.…”

Section: Nigrostriatal Interaction and Neurodegenerative Disordersmentioning

confidence: 99%

Nigrostriatal interaction in the aging brain: new therapeutic target for Parkinson’s disease

Błaszczyk¹

2017

Acta Neurobiologiae Experimentalis

View full text Add to dashboard Cite

Parkinson's disease (PD) is a progressive neurodegenerative disorder of unclear etiology and pathogenesis. Research results gathered to date support the hypothesis that the motor symptoms of the disease result from the gradual loss of midbrain dopamine neurons residing in the substantia nigra pars compacta (SNpc). Recent discoveries, however, significantly expand this knowledge indicating that the primary source of the PD pathogenesis may be located both in the SNpc as well as in the GABAergic striatum. Newly discovered striatal neurogenesis -normally a lifelong process -determines the efficiency of nigrostriatal interaction. Deficient neurogenesis within the striatum followed by a decline in the GABAergic/dopaminergic interaction results in progressive disconnection of the dopaminergic input, which initiates a 'vicious circle' cascade of neuronal damage. Effects of both deficient striatal neurogenesis and age-related neurodegeneration within the striatum accumulate, resulting in a progressive decline in the control functions of the basal ganglia, loss of dopaminergic neurons, and occurrence of PD clinical symptoms. Functional and pharmacological control of these dynamic relationships may result in treatments that are more effective with fewer side-effects.

show abstract

“…Studies report that the disease extends far beyond the dopaminergic nuclei in the mesencephalon (Braak et al, 2003 ;Braak, Ghebremedhin, Rub, Bratzke, & Del Tredici, 2004 ). In fact, patients with PD frequently experience non-motor symptoms, including autonomic, behavioral, and cognitive dysfunctions (Pellicano et al, 2007 ).…”

Section: Introductionmentioning

confidence: 99%

Intensity-dependent facial emotion recognition and cognitive functions in Parkinson’s disease

Assogna

Pontieri

Cravello

et al. 2010

J Int Neuropsychol Soc

Self Cite

View full text Add to dashboard Cite

Patients with Parkinson's disease (PD) frequently display non-motor symptoms. In this study, we investigated intensity-dependent facial emotion recognition in patients with PD and healthy controls (HC), matched for age, gender, and education, and its relationship to individual cognitive domains. Seventy patients with PD and 70 HC were submitted to a clinical, neuropsychological, and psychopathological evaluation. Facial emotion recognition performance was assessed using the Penn Emotion Recognition Test (PERT). The patients with PD recognized fewer low- and high-intensity facial expressions of disgust than HC. This effect was selective, because their global ability to recognize emotions was intact. Both patients with PD and HC recognized high-intensity better than low-intensity emotions, except for disgust, which was recognized better at low intensity. In the patients with PD, overall facial emotion recognition and selective disgust recognition performances were related to deficits in many neuropsychological domains (verbal and visuo-spatial memory, attention, praxis, and verbal fluency). The ability to recognize emotions is a complex cognitive process requiring the integrity of several functions. Therefore, it is likely that structural or functional derangement of the discrete neural pathways involved in these cognitive functions in patients with PD makes it difficult for them to recognize emotions expressed by others.

show abstract

Prodromal non-motor symptoms of Parkinson's disease

Cited by 85 publications

References 76 publications

Surprising behavioral and neurochemical enhancements in mice with combined mutations linked to Parkinson's disease

Surprising behavioral and neurochemical enhancements in mice with combined mutations linked to Parkinson's disease

Nigrostriatal interaction in the aging brain: new therapeutic target for Parkinson’s disease

Intensity-dependent facial emotion recognition and cognitive functions in Parkinson’s disease

Contact Info

Product

Resources

About