Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0030567 (Parkinson's disease)
 63,064 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Patients with neurodegenerative diseases that cause mainly subcortical pathology often exhibit impairment when required to recall lists of unrelated words, but their memories are supposedly improved by test procedures that promote retrieval such as recognition or improve the organization of the to-be-remembered materials. Difficulties with floor effects on free recall and ceiling effects on recognition and other methodological concerns raise doubts about the validity of existing studies that tested these ideas. Using the verbal memory subtests of the RBANS, we [Arch. Clin. Neuropsychol. 18 (2003) 509] expressed each patient's performances on Story Memory, List Learning, Story Recall, List Recall, and List Recognition as Z scores relative to his or her age group. Then, the Z scores were subtracted pairwise to test hypotheses about the nature of memory in Parkinson's disease (PD). Contrary to expectation, patients with PD did not show better immediate or delayed recall of stories relative to lists and they did not show better recognition than recall. In the present investigation, the same methodology was used to study verbal memory in multiple sclerosis, a disease that primarily affects subcortical structures. In contrast to previous results for patients with PD, the patients with MS exhibited better recall of stories than of lists and better List Recognition than Recall. Differences in the pathology of entorhinal regions in PD and MS may contribute to the differing patterns of memory impairment of these patients. The results emphasize that most patients with MS with memory impairments have deficits that are relatively mild and potentially remediable.
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PMID:RBANS analysis of verbal memory in multiple sclerosis. 1528 35

Memory impairment is one of the most common complaints affecting patients with neurodegenerative disorders, and its investigation has provided insights into the function and properties of human memory. The study of Alzheimer's disease has indicated the importance of mesial temporal structures and the hippocampus in episodic memory. In progressive supranuclear palsy, frontotemporal dementias, Parkinson's disease and Huntington's disease fronto-striatal networks are involved in working memory and higher level cognition. The study of semantic dementia, where there is lobar atrophy of the temporal lobe, has shown that the temporal neocortex has an important function in semantic memory. The investigation of human memory in neurodegenerative disorders suggests that the interaction of networks subserving episodic memory, semantic memory, and working memory contributes to higher level cognition and results in the fundamental homeostatic processes of recall and learning.
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PMID:The contribution of the study of neurodegenerative disorders to the understanding of human memory. 1531 24

Trihexyphenidyl (THP) is a drug commonly used to reduce parkinsonian symptoms. An important side effect of this agent is memory impairment. Since caffeine enhances the potency of THP to inhibit haloperidol-induced catalepsy, caffeine may be used as an adjuvant of lower doses of THP, in order to improve its antiparkinsonian effects without causing memory disruption. To further assess the synergism between caffeine and THP, both drugs were tested in reserpinized rats, another preclinical model of Parkinson's disease. Four groups of rats (n = 7) were treated with reserpine (5 mg/kg, i.p.). A control group (n = 7) was treated only with the vehicle for reserpine (dimethylsulphoxide). The spontaneous locomotor behavior was tested 24 h later in a box with infrared sensors, 30 min after receiving one of the following treatments: distilled water (1 ml/kg), caffeine (1 mg/kg), THP (0.1 mg/kg) or caffeine plus THP. The levels of horizontal locomotion (14 +/- 5%) and vertical exploration (15 +/- 10%) were significantly lower in reserpinized rats treated with distilled water, compared with the mean activity values (100%) recorded in animals pretreated only with the vehicle for reserpine. The reserpine-induced hypokinesia was neither reversed by caffeine alone nor by THP alone. However, the combination of caffeine plus THP restored locomotion (141 +/- 19%) and vertical exploration (82 +/- 17%) to levels not significantly different to those of non-reserpinized rats. Moreover, the time-course of locomotion and exploration displayed the characteristic habituation over time, in which short-term memory processes are involved. Also, the thigmotaxis index indicated that the combined treatment did not induce anxiety-like behavior. Hence, these results support the proposal that low, subthreshold doses of caffeine plus THP have the potential to alleviate the motor disabilities in parkinsonian patients, with a low risk of causing anxiety or memory impairment.
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PMID:Treatment with subthreshold doses of caffeine plus trihexyphenidyl fully restores locomotion and exploratory activity in reserpinized rats. 1533 59

Memory deficit in rats treated with scopolamine was rescued by several synthetic retinoids, RAR-ligands (Am80, Am555S, Tp80) and an RXR-ligand (HX630). These results may have implications for the treatment of Alzheimer's disease, age-related dementia, Parkinson's disease, and other neurological disorders.
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PMID:A synthetic retinoid Am80 (tamibarotene) rescues the memory deficit caused by scopolamine in a passive avoidance paradigm. 1551 44

The authors examined the nature of the working memory deficit in persons with Parkinson's disease (PD). Three hypotheses were tested: a limited storage capacity, an impaired executive component, and a reduction of psychomotor speed. Verbal working memory was assessed in 14 PD patients without dementia and 14 matched control participants. Participants were administered a classical verbal span test, working memory tasks that required either updating or manipulation capacities, and motor and psychomotor speed tasks. Patients' performance was comparable to that of control participants on the verbal span test. However, results on the working memory tasks indicated a deficit in manipulation with normal updating capacities. Motor and psychomotor slowing were found in the patient group, but slowing could not fully account for the impairment observed in the manipulation task. Results indicated that there is a genuine but selective working memory impairment in patients with PD.
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PMID:Study of verbal working memory in patients with Parkinson's disease. 1565 68

Adult male Wistar rats with bilateral substantia nigra, pars compacta (SNc) lesion induced by intranigral administration of 0.5 mumol 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) were used as a model of early phase Parkinson's disease (PD). This treatment caused loss of dopaminergic cells in the SNc and a partial depletion of striatal dopamine. Animals trained up to 80% correct choices presented significantly worse scores after SNc lesion compared to sham-operated animals and spent almost 6 days to reach this criterion again, while sham-operated animals reached this criterion within about 2 days. When naive animals had their SNc lesioned before training, they scored worse than sham-operated animals and took 18 days to reach the 80% correct choices criterion, while sham-operated controls reached this criterion after only 10 days. These results suggest that lesion of the SNc impairs working memory in rats performing this task, in agreement with the working memory impairment in PD patients reported in clinical studies.
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PMID:Lesion of the substantia nigra, pars compacta impairs delayed alternation in a Y-maze in rats. 1569 27

Neurocognitive functions have been studied in 100 patients with Parkinson's disease (PD). PD was associated with cognitive impairment due to frontal lobes dysfunction, with hippocampus and right hemisphere involvement in advanced stages of the disease. Severity of cognitive impairment increased simultaneously with severity of movement disorder. Patient's age correlated with cognitive abilities. Mild dementia developed in the oldest patients with advanced PD. Besides typical cognitive disturbances, there were more pronounced memory impairment and speech disorders in some patients that might be related to concomitant pathology.
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PMID:[Cognitive dysfunction in patients with Parkinson's disease]. 1570 77

The monoamine-oxidase-B (MAO-B) inhibitor l-deprenyl (selegiline) is effective in treating Parkinson's disease and possibly cognitive deficits associated with aging, Alzheimer's disease and HIV dementia. The aim of the present study was to investigate the effects of l-deprenyl on short- and long-term recognition memory in aged rats. Young adult and aged male Wistar rats were trained in a novel object recognition task. Retention test trials were carried out at 1.5 or 24 h after training. Aged rats showed impaired recognition memory retention 24 h after training when compared to young animals. Treatment with a daily systemic injection of l-deprenyl (1.0 mg/kg) for 21 days reversed the memory impairment. A control experiment indicated that l-deprenyl did not affect sensorimotor functions. The results suggest that l-deprenyl reverses age-related deficits in long-term recognition memory.
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PMID:Reversal of age-related deficits in object recognition memory in rats with l-deprenyl. 1593 94

Excess of iron in the brain has been implicated in the pathogenesis of several human neurodegenerative diseases, for example Alzheimer's disease and Parkinson's disease. It has been shown that the neonatal period is critical for the establishment of normal iron content in the adult brain. Moreover, it is known that aging alters the cerebral distribution of this metal. We have recently described that neonatal administration of iron severely impaired novel object recognition memory in rats. The aim of the present study was to determine whether selegiline, a monoamine oxidase (MAO) inhibitor known for its neuroprotective properties, could protect rats against cognitive impairment induced by neonatal administration of iron. In the first experiment, male Wistar rats received vehicle (5% sorbitol in water) or iron (10.0 mg/kg) orally from postnatal days 12 to 14 and saline (0.9% NaCl) or selegiline (1.0 or 10.0 mg/kg) intraperitoneally for 21 days, starting 24 h before the first iron dosing. In the second experiment, rats were given either vehicle or iron (10.0 mg/kg) orally from postnatal days 12 to 14 followed by saline or selegiline (1.0 or 10.0 mg/kg) intraperitoneally for 21 days, starting when rats reached adulthood (50th day after birth). Iron-treated rats given selegiline in both doses showed no deficits in recognition memory. Rats receiving iron but no selegiline presented memory deficits. This is the first study reporting the reversion of iron-induced memory impairment, supporting the view that our model can be considered as a useful tool in the search for new drugs with neuroprotective and/or memory enhancing properties.
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PMID:Selegiline protects against recognition memory impairment induced by neonatal iron treatment. 1612 36

Since the discovery of an endogenous cannabinoid system, research into the pharmacology and therapeutic potential of cannabinoids has steadily increased. Two subtypes of G-protein coupled cannabinoid receptors, CB(1) and CB(1), have been cloned and several putative endogenous ligands (endocannabinoids) have been detected during the past 15 years. The main endocannabinoids are arachidonoyl ethanolamide (anandamide) and 2-arachidonoyl glycerol (2-AG), derivatives of arachidonic acid, that are produced "on demand" by cleavage of membrane lipid precursors. Besides phytocannabinoids of the cannabis plant, modulators of the cannabinoid system comprise synthetic agonists and antagonists at the CB receptors and inhibitors of endocannabinoid degradation. Cannabinoid receptors are distributed in the central nervous system and many peripheral tissues, including immune system, reproductive and gastrointestinal tracts, sympathetic ganglia, endocrine glands, arteries, lung and heart. There is evidence for some non-receptor dependent mechanisms of cannabinoids and for endocannabinoid effects mediated by vanilloid receptors. Properties of CB receptor agonists that are of therapeutic interest include analgesia, muscle relaxation, immunosuppression, anti-inflammation, antiallergic effects, improvement of mood, stimulation of appetite, antiemesis, lowering of intraocular pressure, bronchodilation, neuroprotection and antineoplastic effects. The current main focus of clinical research is their efficacy in chronic pain and neurological disorders. CB receptor antagonists are under investigation for medical use in obesity and nicotine addiction. Additional potential was proposed for the treatment of alcohol and heroine dependency, schizophrenia, conditions with lowered blood pressure, Parkinson's disease and memory impairment in Alzheimer's disease.
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PMID:Cannabinoids. 1626 85


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