ABSTRACT
To investigate the difference in results according to the mode of levodopa administration and the effect of zonisamide (ZNS), we analyzed the mRNA expression of dopaminergic and non-dopaminergic receptors in the striatum of Parkinson model rats in relation to the development of levodopa-induced dyskinesia (LID). Unilateral Parkinson model rats were subdivided into 4 groups and treated as follows: no medication (group N), continuous levodopa infusion (group C), intermittent levodopa injection (group I), and intermittent levodopa and ZNS injection (group Z). Two weeks after the treatment, LID was observed in group I and Z, but less severe in group Z. The level of both D1 and D2 receptor mRNAs was elevated in groups I and Z, but only D2 receptor mRNA expression was elevated in group C. Adenosine A2A receptor mRNA showed increased expression only in group I. The level of endocannabinoid CB1 receptor mRNA was elevated in groups N, C, and I, but not in group Z. Intermittent injection of levodopa caused LID, in association with elevated expression of D1 and A2A receptors. ZNS ameliorated the development of LID and inhibited up-regulation of A2A and CB1 receptors. Modulation of these receptors may lead to therapeutic approaches for dyskinesia.
Subject(s)
Anticonvulsants/pharmacology , Corpus Striatum/drug effects , Dopamine Agents/pharmacology , Dyskinesia, Drug-Induced/drug therapy , Gene Expression/drug effects , Isoxazoles/pharmacology , Levodopa/pharmacology , Parkinson Disease/drug therapy , Receptor, Adenosine A2A/drug effects , Receptor, Cannabinoid, CB1/drug effects , Receptors, Dopamine D1/drug effects , Receptors, Dopamine D2/drug effects , Animals , Anticonvulsants/administration & dosage , Dopamine Agents/administration & dosage , Dopamine Agents/adverse effects , Dyskinesia, Drug-Induced/metabolism , Female , Isoxazoles/administration & dosage , Levodopa/administration & dosage , Levodopa/adverse effects , Rats , Rats, Sprague-Dawley , ZonisamideABSTRACT
OBJECTIVES: To clarify whether weight change in patients with Parkinson's disease (PD) or progressive supranuclear palsy (PSP) is caused by the disease itself or secondarily by other factors. MATERIALS AND METHODS: We conducted a retrospective analysis of 51 patients with PD and 14 patients with PSP, especially during the early stage of their diseases. All patients were independent in terms of their activities of daily living and did not have any feeding difficulty. RESULTS: The body mass index measured within 3 years after the disease onset did not show a significant difference between the two diseases. However, the subsequent weight was stable in patients with PD and significantly decreased in patients with PSP. CONCLUSIONS: Weight loss begins in the early stage of PSP, whereas dopaminergic treatment may contribute to keep weight in the early stage of PD through reduction of energy expenditure and/or improvement in appetite.
Subject(s)
Body Mass Index , Disease Progression , Parkinson Disease/physiopathology , Supranuclear Palsy, Progressive/physiopathology , Weight Loss/physiology , Aged , Female , Humans , Male , Middle Aged , Retrospective StudiesABSTRACT
A 64-year-old man noticed weakness in his arms and dyspnea upon exertion. Four months later he was admitted to our hospital, where muscle atrophy and hyperactive deep tendon reflexes in the arms were observed upon examination. A needle electromyograph study revealed acute and chronic denervation in the extremities, and he was diagnosed as having amyotrophic lateral sclerosis (ALS). Seven months after onset of the disease, he died of respiratory failure. Neuropathologically, neuronal cell loss was observed in the motor cortex, hypoglossal nuclei, cervical and lumbar anterior horns and Clarke's nuclei. Some of the remaining neurons contained neurofilamentous conglomerate inclusions (CIs). A small number of Lewy body-like hyaline inclusions (LBHIs) were also observed. No the Bunina bodies, skein-like inclusions or basophilic inclusions were detectable. Tract degeneration was moderate in the dorsal and ventral spinocerebellar tracts, mild in the pyramidal tract, but not discerned in the posterior column. Immunohistochemical examinations revealed that the CIs were strongly positive for phosphorylated neurofilament and moderately positive for ubiquitin and Cu/Zn superoxide dismutase 1 (SOD1). Moreover, a number of phosphorylated tau protein-positive globose neurofibrillary tangles (NFTs) and threads were observed in the periaqueductal gray matter, oculomotor nuclei and trochlear nuclei. Although the family history was negative for neuromuscular diseases, the neuropathological findings indicated features of familial ALS with a SOD1 mutation. In fact, DNA analysis of frozen-brain tissue revealed the presence of the I113Tâ SOD1 mutation. This case represents the first one of this mutation in a patient who showed CIs as well as LBHIs in the motor neurons at the same time, in addition to the NFTs in the mesencephalic tegmentum.
