Journal of Neural Transmission - Parkinson's Disease and Dementia Section最新文献

{"title":"Are NMDA antagonistic properties relevant for antiparkinsonian-like activity in rats?--case of amantadine and memantine.","authors":"W Danysz,&nbsp;M Gossel,&nbsp;W Zajaczkowski,&nbsp;D Dill,&nbsp;G Quack","doi":"10.1007/BF02253435","DOIUrl":"https://doi.org/10.1007/BF02253435","url":null,"abstract":"<p><p>Amantadine (25, 50, 100 mg/kg), memantine (5, 10, 20 mg/kg) and MK-801 (0.05, 0.1, 0.2 mg/kg), all having NMDA channel blocking properties, were compared in three tests used for screening of antiparkinsonian agents in rats, namely: haloperidol-induced catalepsy, locomotor activity in monoamine depleted rats and rotation in rats with a unilateral substantia nigra lesion. Additionally, plasma levels of amantadine and memantine were assessed to gain an insight into the concentration ranges achieved at behaviorally active doses. Amantadine and (+)-MK-801 produced dose-dependent inhibition of haloperidol-induced catalepsy while memantine was less efficacious producing clear-cut anticataleptic action at a dose of 10 mg/kg only but failing at 20 mg/kg due to myorelaxant activity. All agents attenuated sedation in monoamine depleted rats with amantadine being the least and MK-801 being the most effective. The same rank order of efficacy was seen in inducing ipsilateral rotations in rats after a substantia nigra lesion. On the basis of the present study and published data, it can be assumed that the doses of amantadine, memantine and MK-801 showing antiparkinsonian-like activity in animals result in plasma levels leading to NMDA antagonism. However, in the haloperidol-induced catalepsy test the efficacy of amantadine was higher than memantine, while the opposite was true for rotation and reserpine-induced sedation indicating pharmacodynamic differences between both agents.</p>","PeriodicalId":16466,"journal":{"name":"Journal of Neural Transmission - Parkinson's Disease and Dementia Section","volume":"7 3","pages":"155-66"},"PeriodicalIF":0.0,"publicationDate":"1994-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/BF02253435","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18714052","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pyritinol facilitates the recovery of cortical cholinergic deficits caused by nucleus basalis lesions.","authors":"A Toledano,&nbsp;M L Bentura","doi":"10.1007/BF02253438","DOIUrl":"https://doi.org/10.1007/BF02253438","url":null,"abstract":"<p><p>The effect of a nootropic, Pyritinol, on the recovery of cortical cholinergic deficits induced by injury of the nucleus basalis has been tested on two groups of unilateral quisqualic acid nbM-lesioned rats. The first group had a 30 nmol lesion producing a cortical cholinergic impairment at 21 days, with a spontaneous recovery at 45 days. The second group had a 50 nmol lesion that produced a deeper cholinergic deficit, which did not recover at 45 days. Pyritinol enhanced the recovery in the 30 nmol group of animals on the 21st day after surgery. The recovery was measured as an increase in the activities of acetylcholinesterase (AChE), choline acetyltransferase (ChAT) and the high affinity choline uptake system, and the histochemical densities of the cortical AChE network and the M2 receptor. Histochemical analysis of the nbM enabled cortical recovery to be related to the number of surviving neurons and also to their hypertrophy and AChE-ChAT hyperactivity. Pyritinol enhanced recovery in 30 nmol lesioned animals but in the other group, with a lower number of surviving neurons and a lower ability of the cells to become hypertrophic, the drug was unable to promote cortical recovery.</p>","PeriodicalId":16466,"journal":{"name":"Journal of Neural Transmission - Parkinson's Disease and Dementia Section","volume":"7 3","pages":"195-209"},"PeriodicalIF":0.0,"publicationDate":"1994-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/BF02253438","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18714744","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Intranigral injected iron progressively reduces striatal dopamine metabolism.","authors":"W Wesemann,&nbsp;S Blaschke,&nbsp;M Solbach,&nbsp;C Grote,&nbsp;H W Clement,&nbsp;P Riederer","doi":"10.1007/BF02260941","DOIUrl":"https://doi.org/10.1007/BF02260941","url":null,"abstract":"<p><p>The striatal dopamine metabolism of the rat was followed 1, 3, and 6 weeks after unilateral intranigral iron (III) (50- and 1.5 micrograms) application. For both concentrations a progredient decrease of extraneuronal 3.4-dihydroxyphenylacetic acid (DOPA) levels was observed in the ipsilateral striatum.</p>","PeriodicalId":16466,"journal":{"name":"Journal of Neural Transmission - Parkinson's Disease and Dementia Section","volume":"8 3","pages":"209-14"},"PeriodicalIF":0.0,"publicationDate":"1994-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/BF02260941","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18749738","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reference memory is affected by transient bilateral clamping of the carotid arteries in rats (BCCA).","authors":"C Heim,&nbsp;K H Sontag","doi":"10.1007/BF02252662","DOIUrl":"https://doi.org/10.1007/BF02252662","url":null,"abstract":"<p><p>Rats were subjected to 60 min of bilateral clamping of the carotid arteries (BCCA) in pentobarbital anaesthesia and tested in a hole board with 8 of the 25 holes baited with food pellets hidden in a serial order. All rats learned to recognize the pattern as a reference during an acquisition period at 2-14 days post surgery, i.e. reference memory. During the recall tests 29-37, 165-175 and 240-250 days later BCCA animals showed a decrease in memory revealing a significant increase in reference memory errors. The number of working memory errors, i.e. reexamination of inspected previously baited holes, did not differ from those of sham operated controls. The number of pellets eaten in serial order from hole 1 to hole 8 was significantly decreased in BCCA animals compared with controls, while the number of holes inspected by the animals in the two groups were the same. Thus the observed behaviour changes appear not to be caused by motor or motivation deficiencies.</p>","PeriodicalId":16466,"journal":{"name":"Journal of Neural Transmission - Parkinson's Disease and Dementia Section","volume":"7 1","pages":"47-59"},"PeriodicalIF":0.0,"publicationDate":"1994-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/BF02252662","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19560262","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The clinimetrics of hypokinesia in Parkinson's disease: subjective versus objective assessment.","authors":"J J van Hilten,&nbsp;J I Hoff,&nbsp;H A Middelkoop,&nbsp;R A Roos","doi":"10.1007/BF02250922","DOIUrl":"https://doi.org/10.1007/BF02250922","url":null,"abstract":"<p><p>In this study we evaluate the feasibility of measures that reflect different characteristics of motor activity and immobility in the objective quantification of hypokinesia. Because by definition hypokinesia can only be assessed over a period of time, continuous activity monitoring was used during 5 successive days in the home setting in 64 patients with Parkinson's disease (PD) and 104 healthy elderly subjects. In the patients we also evaluated the relation between the monitor measures and subjective measures of hypokinesia and age. Compared to the healthy elderly subjects, PD patients have a decreased activity level, increased proportion of time without movement, elevated mean duration of immobility, and decreased percentage of short-lasting immobility periods. Differences between both groups were most prominent for those measures that incorporate or reflect immobility. Moreover, in the PD patients the mean duration of immobility and percentage of short-lasting immobility periods show an apparent lack of relation with age and clinical ratings obtained from the UPDRS. In conclusion, our findings underscore the poor representation of hypokinesia in the UPDRS and value of objective quantification of this fundamental impairment of PD.</p>","PeriodicalId":16466,"journal":{"name":"Journal of Neural Transmission - Parkinson's Disease and Dementia Section","volume":"8 1-2","pages":"117-21"},"PeriodicalIF":0.0,"publicationDate":"1994-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/BF02250922","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18890431","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Quantification of mRNA of tyrosine hydroxylase and aromatic L-amino acid decarboxylase in the substantia nigra in Parkinson's disease and schizophrenia.","authors":"H Ichinose,&nbsp;T Ohye,&nbsp;K Fujita,&nbsp;F Pantucek,&nbsp;K Lange,&nbsp;P Riederer,&nbsp;T Nagatsu","doi":"10.1007/BF02250926","DOIUrl":"https://doi.org/10.1007/BF02250926","url":null,"abstract":"<p><p>Using the reverse transcription-polymerase chain reaction (RT-PCR), we developed a sensitive and quantitative method to detect all four types of human tyrosine hydroxylase (TH) mRNAs in the human brain (substantia nigra). All four types of TH mRNAs were found in the substantia nigra in the control brains examined, and the ratio of type-1, type-2, type-3, and type-4 mRNAs to the total amount of TH was 45, 52, 1.4, and 2.1%, respectively. The average amount of total TH mRNA in the normal brain (substantia nigra) was 5.5 amol of TH mRNA per microgram of total RNA. The ratios of four TH isoforms were not altered significantly in Parkinson's disease or schizophrenia. Further we measured the relative amount of aromatic L-amino acid decarboxylase (AADC) and beta-actin mRNAs in the brain samples. TH and AADC mRNAs were highly correlated in the control cases. We found that parkinsonian brains had very low levels of all four TH isoforms and AADC mRNAs in the substantia nigra compared with control brains, while no significant differences were found between schizophrenic brains and normal ones. Since the decrease in AADC mRNA was comparable to that in TH mRNA, the alteration of TH in Parkinson's disease would not be a primary event, but it would reflect the degeneration of dopaminergic neurons in the substantia nigra. This is the first reported measurement of mRNA contents of TH isoforms and AADC in Parkinson's disease and schizophrenia.</p>","PeriodicalId":16466,"journal":{"name":"Journal of Neural Transmission - Parkinson's Disease and Dementia Section","volume":"8 1-2","pages":"149-58"},"PeriodicalIF":0.0,"publicationDate":"1994-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/BF02250926","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18890435","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Protective effects of 5-HT1A receptor agonists against neuronal damage demonstrated in vivo and in vitro.","authors":"B Peruche,&nbsp;C Backhauss,&nbsp;J H Prehn,&nbsp;J Krieglstein","doi":"10.1007/BF02250918","DOIUrl":"https://doi.org/10.1007/BF02250918","url":null,"abstract":"<p><p>The aim of the present study was to evaluate the neuroprotective effect of the 5-hydroxytryptamine1A (5-HT1A) agonists, CM 57493 and urapidil, in vivo and in vitro, respectively. In vivo permanent occlusion of the middle cerebral artery (MCA) was performed in male Wistar rats. Forty-eight hours after electrocoagulation of the MCA the infarct volume was determined. Pretreatment of the rat with the 5-HT1A agonist urapidil significantly reduced infarct development. The neuroprotective effect of the agent was restricted to the cortical area; the striatal damage was not influenced. As the stimulation of the 5-HT1A receptor by serotonin is supposed to induce inhibitory, hyperpolarizing effects by opening of a Ca(2+)-independent neuronal K+ ionophore, the efficacy of agonistic drugs directly on the neuron was investigated in vitro. Cyanide-induced cytotoxic hypoxia as well as glutamate-induced excitotoxicity were performed using primary neuronal cell cultures from chick embryo cerebral hemispheres. Treatment with the 5-HT1A agonists urapidil and CM 57493 significantly increased protein content of hypoxic cultures. CM 57493 added to the culture medium (1-10 microM) during and up to 24 h after glutamate exposure ameliorated viability of the neurons. The results demonstrate neuroprotective potency of the 5-HT1A agonists, urapidil and CM 57493, when applied under hypoxic, excitotoxic and ischemic conditions in vivo and in vitro, respectively. Both, presynaptically induced inhibition of glutamate release as well as postsynaptically induced inhibition of neuronal excitability could be discussed as possible mechanisms of action of the 5-HT1A receptor agonism.</p>","PeriodicalId":16466,"journal":{"name":"Journal of Neural Transmission - Parkinson's Disease and Dementia Section","volume":"8 1-2","pages":"73-83"},"PeriodicalIF":0.0,"publicationDate":"1994-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/BF02250918","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18890436","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetic factors in the etiology of idiopathic Parkinson's disease.","authors":"P Vieregge","doi":"10.1007/BF02250916","DOIUrl":"https://doi.org/10.1007/BF02250916","url":null,"abstract":"<p><p>Overshadowed by a vigorous search for an environmentally-derived toxin that would be possibly relevant for the pathogenesis of idiopathic Parkinson's disease (PD), genetic factors have largely been neglected for this condition during the last two decades. Recent descriptions of kindreds over three or more generations with several family members affected have renewed the interest in genetics of PD. Concurring with this, diagnostic concepts and pathologic criteria for PD and for idiopathic Lewy-body (LB) disease have been reevaluated such that LB-proven parkinsonism is sufficiently differentiated from familial parkinsonism without LB pathology. Surveys on genetic epidemiology in PD have confirmed the 19th century's notion that 10 to 15% of PD index cases report a further family member with PD. These figures were, however, substantiated on a statistical basis only in single surveys when comparisons were made with the numbers of PD relatives in control index cases. Twin studies did not reveal a higher rate of concordance within monozygotic pairs than in dizygotic pairs. Tests of striatal 18-F-Dopa uptake in clinically unaffected mono- and dizygotic co-twins did not alter the ratio between the concordance rates. Though not excluded by the twin studies, multifactorial (or polygenic) inheritance as well as mitochondrial inheritance are at present less likely to cover most of the inheritance pattern in familial LB parkinsonism. Instead, autosomal dominant inheritance with reduced penetrance is the most probable inheritance pattern for most of the reported pedigrees. Molecular genetic investigations have to consider the biochemical basis of the age- and region-specific pathology of PD. The first analyses of linkage and allelic associations gave inconclusive results in sporadic and familial PD. The hunt for metabolic factors that link geno- and phenotype expression in PD will continue.</p>","PeriodicalId":16466,"journal":{"name":"Journal of Neural Transmission - Parkinson's Disease and Dementia Section","volume":"8 1-2","pages":"1-37"},"PeriodicalIF":0.0,"publicationDate":"1994-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/BF02250916","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18891796","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A new metabolic pathway of L-threo-3,4-dihydroxyphenylserine, a precursor amino acid of norepinephrine, in the brain. Studies by in vivo microdialysis.","authors":"W Maruyama,&nbsp;D Nakahara,&nbsp;M Naoi","doi":"10.1007/BF02252660","DOIUrl":"https://doi.org/10.1007/BF02252660","url":null,"abstract":"<p><p>The metabolism and the effects of L-threo-3,4-dihydroxyphenylserine (L-threo-DOPS) were studied in the rat brain striatum by in vivo microdialysis. In the brain L-threo-DOPS was metabolized by 3 different enzymes; aromatic L-amino acid decarboxylase, catechol-O-methyltransferase, and DOPS-aldolase. DOPS-aldolase was the main enzyme which metabolizes L-threo-DOPS. The amounts of the metabolites by L-amino acid decarboxylase (norepinephrine and its metabolites) were 0.4% of the total amounts of metabolites detected in the dialysate, while those by catechol-O-methyltransferase, 2.1%, and by DOPS-aldolase, 97.5%, after 100 min perfusion of L-threo-DOPS. L-threo-DOPS was found to increase extracellular levels of dopamine and serotonin, and to inhibit monoamine catabolism in the brain. Inhibition of DOPS-aldolase should improve its effectiveness as the supplement therapy of norepinephrine.</p>","PeriodicalId":16466,"journal":{"name":"Journal of Neural Transmission - Parkinson's Disease and Dementia Section","volume":"7 1","pages":"21-33"},"PeriodicalIF":0.0,"publicationDate":"1994-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/BF02252660","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19560260","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A comparison of multiplex and simplex families with Alzheimer's disease/senile dementia of Alzheimer type within a well defined population.","authors":"I Alafuzoff,&nbsp;E Almqvist,&nbsp;R Adolfsson,&nbsp;S Lake,&nbsp;W Wallace,&nbsp;D A Greenberg,&nbsp;B Winblad","doi":"10.1007/BF02252663","DOIUrl":"https://doi.org/10.1007/BF02252663","url":null,"abstract":"<p><p>A study was made on 150 clinically demented patients presenting at autopsy at Umeå University Hospital in Sweden. In 90 of the cases dementia was considered to be primary in nature and of these forty six per cent (41 cases), fulfilled both the clinical and histopathological criteria for the diagnosis of Alzheimer's disease/Senile dementia of Alzheimer type (AD/SDAT). The families of these 41 AD/SDAT cases were then studied, and a family history obtained through interviews with multiple family informants and from civil and medical records. Additional diseased family members suffering from progressive dementia (multiplex families) were observed in 12 probands out of 41 (29%). Multiplex families exhibited similar clinical and histopathological characteristics as simplex families containing a single affected individual. The secondary cases in the multiplex families exhibited similar demographic and clinical characteristics as the probands. 39% of the multiplex and 14% of the simplex cases had an early age of onset of the disease, that was under 65 years. The overall prevalence of progressive dementia disorders in the 41 families was 5.9%. The prevalence of a progressive dementia disorder was 11% in the multiplex families (14% for the early onset cases) and 3.5% in the simplex families (2% for the early onset cases). The prevalence of progressive dementia disorder for family members who had passed the mean age of the onset of the disease for their family, was 45% for multiplex and 18% for simplex families. Furthermore the incidence rate for dementia was significantly higher (p < 0.005) in multiplex families (5.5 per 1,000 person years) when compared to simplex families (2.5 per 1,000 person years). No differences could be seen in parental age at birth of the diseased when comparing the two sets of families. However in multiplex families the duration of the disease was significantly (p < 0.025) shorter, in subjects with parental age at birth over 35 years compared to those with a parental age under 35 years. The multiplex families contained significantly (p < 0.025) larger sibships; and showed a significantly lower age of onset for the disease (p < 0.001), and a significantly longer duration of disease (p < 0.05) compared to the simplex families. A significant intra familial correlation of age at disease onset was observed in both sets of the families.</p>","PeriodicalId":16466,"journal":{"name":"Journal of Neural Transmission - Parkinson's Disease and Dementia Section","volume":"7 1","pages":"61-72"},"PeriodicalIF":0.0,"publicationDate":"1994-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/BF02252663","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19560263","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}