Lipopolysaccharide-induced functional and structural injury of the mitochondria in the nigrostriatal pathway.

Accumulating evidence suggests that chronic inflammation plays a role in the progressive dopaminergic neurodegeneration that occurs in Parkinson's disease. It has been hypothesized that inflammation mediates neuronal damage via exacerbation of a vicious cycle of oxidative stress and mitochondrial dysfunction. The bacterial endotoxin, lipopolysaccharide (LPS), induces microglial activation and inflammation driven dopaminergic neurodegeneration. In order to test the hypothesis that LPS-induced inflammatory response might damage mitochondrial structure and function leading to nigral dopaminergic neuron loss, we injected LPS or saline into the striatum of rats. Here, we found that intrastriatal LPS induced deficit in mitochondrial respiration, damage to mitochondrial cristae, mitochondrial oxidation and nitration. Finally, we found significant loss of dopaminergic neurons in the substantia nigra one week after LPS injection. This study indicates that LPS-induced dopaminergic neurodegeneration might be exerted by mitochondrial injury.

Cardiac sympathetic impairment parallels nigrostriatal degeneration in Probable Dementia with Lewy Bodies.

AIM: Dementia with Lewy Bodies (DLB) must be distinguished from other types of dementia because of important differences in patient management and outcome. Both reduction in cardiac 123I-metaiodobenzilguanidine (MIBG) uptake and decreased 123I-FP-CIT binding in basal ganglia have been described in DLB. The aim of this study was to assess the relationship between cardiac sympathetic activity and nigrostriatal degeneration in patients with probable DLB. METHODS: Twenty-eight patients (15 males; mean age 77 years, range 64-88 years) with clinical international criteria of probable DLB were included in the study. All patients underwent a cardiac MIBG scintigraphy and a FP-CIT SPECT. Global cardiac MIBG uptake was semiquantified by means of heart-to-mediastinum ratio (HMR) (normal >1.56). FP-CIT binding in basal ganglia was calculated and compared with an age-matched control group. The relation between cardiac MIBG uptake and FP-CIT uptake in basal ganglia, and the relationship of these two techniques with distinctive symptoms of DLB, features of past medical history and data from the neuropsychological examination were assessed. RESULTS: Cardiac MIBG uptake was decreased in 23 of 28 patients (HMR=1.32, range 0.95-1.85). The FP-CIT binding in basal ganglia was significantly lower than in control group (2.01±0.5 vs 2.62±0.2, P<0.05). All patients with reduced cardiac HMR showed decreased FP-CIT binding in basal ganglia. There was a positive correlation between the HMR and specific binding ratio of striatum (P<0.01). A high correlation between FP-CIT SPECT and the presence of parkinsonism also was found. No correlation between cardiac MIBG uptake and demographic, clinical or neuropsychological data was found. CONCLUSION: In probable DLB cardiac MIBG uptake and FP-CIT binding in basal ganglia are reduced. The positive correlation between both measures suggests that cardiac sympathetic degeneration and nigrostriatal degeneration parallel similarly in patients with probable DLB.

Motor neuron disease with dementia combined with degeneration of striatonigral and pallidoluysian systems.

This study concerns an autopsy case of motor neuron disease with dementia (MND-D) that exhibited unusual clinical and neuropathological findings. The patient was a Japanese man without any relevant family history who was 60 years old at the time of death. His clinical manifestation included character change at the age of 54, followed by frozen gait, dysarthria and bradykinesia and he was diagnosed with Parkinson's disease. He gradually developed spastic paresis and died of respiratory failure 6 years after onset of the illness. Neuropathological examinations showed prominent degeneration in the striatonigral and pallidoluysian systems in addition to the neuronal loss and microvacuolation in the second to third layers of the frontal and temporal cortex, the involvement of the upper and lower motor neuron systems and the presence of ubiquitinated neuronal inclusions. To our knowledge, five cases of motor neuron disease (MND) combined with pallido-nigro-luysian atrophy (PNLA) have been reported previously, but the present case is the first report of MND-D combined with the degeneration of the striatonigral and pallidoluysian systems. Such an association may represent more than a coincidental occurrence, and it suggests that MND-D is not simply a disease of the motor neuron system but a multisystem degeneration.

Relación entre las alteraciones visoespaciales y los parámetros oculomotores en la enfermedad de Parkinson / Relationship between visuospatial impairment and oculomotor parameters in Parkinson's disease

Se han estudiado las funciones visoespaciales y los parámetros oculomotores en una muestra de 96 pacientes afectados por Enfermedad de Parkinson 8EP). Los déficit visoespaciales han correlacionado con el deterioro a nivel motor y la gravedad de la enfermedad, así como con las anormalidades oculomotoras. Se realizaron correlaciones parciales con la finalidad de determinar si las alteraciones visoespaciales podían considerarse secundarias a los trastornos oculomotores. Las pruebas de Cubos de las Escala WAIS y el Test de Orientación de Líneas mantenían su correlación con la alteración motora y la gravedad de la enfermedad, tras haber controlado las variables de persecución y los movimientos sacádicos. En síntesis, los resultados del presente estudio muestran que los déficits visoespaciales no pueden ser explicados por anormalidades oculomotoras en los pacientes con EP, pudiendo considerarse ambos expresión del defecto estriatal (AU)

Visuospatial functions and oculomotor parameters were studied in a sample of 96 patients with Parkinson’s Disease (PD). Visuospatial deficits correlated with both motor impairment and severity of illness, as well as with oculomotor abnormalities. Partial correlations were performed to determine whether visuospatial impairment was secondary to oculomotor disorders. After controlling for gaze pursuit variables and saccades, Block Design (WAIS) and Line Orientation Test maintained their correlations with motor impairment and severity of illness. In conclusion, the results of the present study show that visuospatial deficits cannot be explained through oculomotor abnormalities in PD patients, pointing to a simultaneous expression of striatum dysfunction (AU)