Psychiatric aspects of Parkinson?s disease

Schrag, Anette

doi:10.1007/s00415-004-0483-3

Cited by 186 publications

(105 citation statements)

References 92 publications

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“…The age-related and progressive signs of PD classically include resting tremor, muscular rigidity, abnormal gait, and slow movement; however, other signs and symptoms associated with parkinsonism can include somatosensory deficits, impaired cognitive function, and psychiatric disturbances (2)(3)(4). Many PD signs result from the degeneration of dopaminergic neurons in the substantia nigra pars compacta.…”

mentioning

confidence: 99%

Parkin-deficient mice are not a robust model of parkinsonism

Perez

Palmiter

2005

Proc. Natl. Acad. Sci. U.S.A.

432

339

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Mutations in the human parkin gene cause autosomal recessive juvenile parkinsonism, a heritable form of Parkinson's disease (PD). To determine whether mutations in the mouse parkin gene (Park2) also result in a parkinsonian phenotype, we generated mice with a targeted deletion of parkin exon 2. Using an extensive behavioral screen, we evaluated neurological function, motor ability, emotionality, learning, and memory in aged Parkin-deficient mice. The behavioral profile of Parkin-deficient mice on a B6;129S4 genetic background was strikingly similar to that of control mice, and most differences were not reproducible by using coisogenic mice on a 129S4 genetic background. Moreover, catecholamine levels in the striatum, olfactory bulb, and spinal cord of Parkin-deficient mice were normal. In contrast to previous studies using independently generated Parkin-deficient mice, we found no evidence for nigrostriatal, cognitive, or noradrenergic dysfunction. Understanding why Parkin-deficient mice do not exhibit robust signs of parkinsonism could advance knowledge and treatment of PD.mouse behavior ͉ dopamine ͉ norepinephrine ͉ gene knockout ͉ Parkinson P arkinson's disease (PD) is a devastating neurodegenerative disorder that affects Ͼ500,000 people in the United States alone (1). The age-related and progressive signs of PD classically include resting tremor, muscular rigidity, abnormal gait, and slow movement; however, other signs and symptoms associated with parkinsonism can include somatosensory deficits, impaired cognitive function, and psychiatric disturbances (2-4). Many PD signs result from the degeneration of dopaminergic neurons in the substantia nigra pars compacta. Dopamine replacement medications often succeed in managing parkinsonism; however, these treatments lose effectiveness, have undesirable effects, and do not prevent the underlying neurodegeneration. Understanding the molecular mechanism of dopaminergic neuron degeneration would facilitate the development of therapies that prevent PD.The identification of mutations in single genes that result in familial parkinsonism will help advance our understanding of the molecular mechanism of PD. Mutations in the human parkin gene are responsible for autosomal recessive juvenile parkinsonism (AR-JP), a heritable disease that resembles PD (5). The Parkin protein is a widely expressed, E3 ubiquitin-protein ligase that is thought to target specific proteins for proteasomal degradation (5-7). Presumably, in the absence of Parkin function, these protein targets accumulate to toxic levels and cause dopamine neuron degeneration.To investigate how mutations in parkin lead to parkinsonism, we generated mice with a targeted disruption of Park2. We hypothesized that Parkin-deficient mice would recapitulate the behavioral signs and pathology of AR-JP. During our investigation, several other groups independently generated and described mice with various targeted deletions of the parkin gene (8-11); however, results from these studies have raised many new issues. First, the b...

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mentioning

confidence: 99%

Parkin-deficient mice are not a robust model of parkinsonism

Perez

Palmiter

2005

Proc. Natl. Acad. Sci. U.S.A.

432

339

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“…The gradual process of increase in resistance to b-lactams is shown by MIC values. Since the 1990s, decreased susceptibility rates to penicillin have been described in many countries, with prevalence rates sometimes higher than 40 % and, occasionally, MICs higher than 8 mg ml 21 (Appelbaum, 2002;Klugman, 1990;Schrag et al, 2004). Nevertheless, in the past few years, some studies have detected a significant decrease in the rates of resistant pneumococci in Europe and the USA with the introduction of the 7-val conjugate vaccine together with a reduction in antibiotic consumption levels (Doern et al, 2005;Kaplan et al, 2004;Oteo et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

Increase in numbers of β-lactam-resistant invasive Streptococcus pneumoniae in Brazil and the impact of conjugate vaccine coverage

Brandileone

Casagrande

Guerra

et al. 2006

Journal of Medical Microbiology

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A comprehensive investigation of invasive Streptococcus pneumoniae was carried out in Brazil as part of the programme of the national epidemiological surveillance system. The investigation provided data on the trends of resistance to antimicrobial agents. A total of 6470 isolates of S. pneumoniae collected in the country from 1993 to 2004 were tested. During this period of time, the number of penicillin-resistant strains rose from 10?2 to 27?9 %. The proportions of intermediate and high-level resistant strains in 1993, which were 9?1 and 1?1 %, respectively, rose to 22?0 and 5?9 % in 2004. Geometric mean MICs for penicillin increased after the year 2000, to 0?19 mg ml "1 in 2004; most of these isolates were from patients with pneumonia and from children under 5 years old, and belonged to serotype 14. There was a significant increase in the number of isolates belonging to serotypes included in the 7-valent conjugate vaccine from children under 5 years old: from 48?6 % in 1993 to 69?6 % in 2004, mainly related to an increase in the frequency of serotype 14 isolates. From 2000 to 2004, meningitis isolates showed higher resistance rates to cefotaxime (2?6 %) compared to non-meningitis isolates (0?7 %); percentages of isolates resistant to trimethoprim-sulfamethoxazole, tetracycline, erythromycin, chloramphenicol and rifampicin were 65, 14?6, 6?2, 1?3 and 0?7 %, respectively. No levoflaxin resistance was observed. Multidrug resistance was identified in 4?6 % of isolates, of which 3?8 % were resistant to three classes, 0?7 % to four classes and 0?1 % to five classes of antimicrobial agent. The study provides valuable information that may support empirical antimicrobial therapy for severe S. pneumoniae infections in Brazil, and emphasizes the need for conjugate pneumococcal vaccination.

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“…According to several cross-sectional surveys, rates of depression range from 20-50 % in PD patients [60]. Some studies have shown that compared with AD patients PDD patients display higher rates of major depression [63] and depressive symptoms [30,45].…”

Section: Behavioral Changes Associated With Pddmentioning

confidence: 98%