Search Results - (Author, Cooperation:J. O. Rinne)

2011-08-06

American Association for the Advancement of Science (AAAS)

0036-8075

1095-9203

Biology

Chemistry and Pharmacology

Computer Science

Medicine

Natural Sciences in General

Physics

Adult ; Corpus Striatum/*metabolism/radionuclide imaging ; Dopamine/*metabolism ; Humans ; *Learning ; Male ; *Memory, Short-Term ; Positron-Emission Tomography ; Raclopride/metabolism ; Receptors, Dopamine D2/*metabolism ; Young Adult

2018-03-06

The Society of Nuclear Medicine (SNM)

0022-3123

Medicine

1471-4159

Blackwell Publishing Journal Backfiles 1879-2005

Medicine

We investigated histamine concentration in post-mortem brain samples of patients with Parkinson's disease (PD, n = 24), multiple system atrophy (MSA, n = 8) and age-matched controls (n = 27). Histamine concentrations were significantly increased in the putamen (to 159% of the control mean), substantia nigra pars compacta (to 201%), internal globus pallidus (to 234%) and external globus pallidus (to 200%), i.e. in areas which play a crucial role in the motor behaviour and which show typical functional alterations in PD. In MSA no significant differences were seen. Tele-methylhistamine (histamine metabolite) concentrations were unchanged in PD. These results indicate that histamine concentration, but not its metabolism is increased in PD, but not in MSA. This finding may have implications in developing new drug therapies for PD and in differential diagnosis between PD and MSA.

Electronic Resource

1460-9568

Blackwell Publishing Journal Backfiles 1879-2005

Medicine

Post mortem studies have revealed a loss of dopamine D2 receptors in the temporal lobes in Alzheimer's disease (AD). Moreover, the role of hippocampal D2 receptors on memory performance has been suggested in experimental studies. However, there are no previous in vivo studies on extrastriatal D2 receptors in AD. Our aim was to examine in vivo whether hippocampal or temporal cortical dopamine D2 receptors are affected in AD and whether D2 receptor availability is associated with the memory dysfunction seen in AD. Fourteen patients with probable AD and 11 age- and sex-matched controls were studied with positron emission tomography using a dopamine D2/D3 receptor antagonist [11C]FLB 457. The D2 receptor binding potentials (BPs) were measured in extrastriatal brain regions and a neuropsychological investigation was performed on the patients with AD. In AD, the D2 receptor availability was reduced in the hippocampus: by 34% (P = 0.03) in the right hippocampus and by 14% (P = 0.78) in the left hippocampus as compared with controls. Multiple linear regression analysis showed that the BP in the right hippocampus had a significant positive association with verbal memory performance (Wechsler Memory Scale – Revised) (P = 0.001) and picture naming (the Boston Naming Test) (P = 0.002). Our findings suggest a role for temporal lobe D2 receptors in the memory and naming performance in AD, and suggest that studies to evaluate the efficiency of dopaminergic medication on patients with early AD might be warranted.

Electronic Resource

1435-1463

Alzheimer's disease ; multi-infarct dementia ; combined dementia ; choline acetyltransferase ; post-mortem brain studies

Springer Online Journal Archives 1860-2000

Medicine

Summary Brain choline acetyltransferase (ChAT) activity was determined in 43 patients with Alzheimer's disease (AD), 14 with multi-infarct dementia (MID), and 15 with combined dementia (CD) and in 53 age-matched controls. The activity of ChAT declined in the hippocampus, temporal and frontal cortex in patients with AD and CD compared to the controls. In the AD group the reduced activity of ChAT in all brain areas was associated with a greater number of cortical neurofibrillary tangles. The degree of dementia had a negative correlation with the activity of ChAT in the frontal cortex in both AD and CD patients. The activity of ChAT in the temporal cortex of CD patients was negatively associated with the cortical tangle counts. In contrast, the activity of ChAT and MID patients was not essentially different from that of the controls. Neither did the various clinical and neuropathological variables show any significant correlation with ChAT activity in MID patients. Thus, in this study the reduction in the activity of ChAT seems to be associated with Alzheimer-type pathology but not with dementia due to vascular changes.

Electronic Resource

1435-1463

Alzheimer's disease ; senile dementia ; multi-infarct dementia ; combined dementia ; dopamine receptors ; post-mortem brain studies

Springer Online Journal Archives 1860-2000

Medicine

Summary Brain dopamine D-2 receptors were analysed in the caudate nucleus, putamen and nucleus accumbens in 49 patients with different types of neuropathologically verified dementia and in 39 controls by the binding of3H-spiroperidol. The binding was significantly decreased in all brain areas in patients with Alzheimer's disease (AD), while the changes in patients with multi-infarct dementia (MID) or combined dementia (CD) were non-significant. According to a Scatchard analysis, this decrease in binding was due to the reduced number of receptors. On the other hand, the binding of3H-spiroperidol was significantly increased in those patients who had received neuroleptic drugs. Significant correlations between3H-spiroperidol binding and neuropathological changes were seen only in AD patients in the nucleus accumbens. The nucleus accumbens was also the only brain area in which there was a significant correlation between dopamine D-2 and the number of muscarinic receptors in AD patients. The findings of this study on dopamine D-2 receptors suggest the involvement of the nigrostriatal dopaminergic system in AD but not in the other two major types of dementia.

Electronic Resource

1432-0533

Key words Parkinson’s disease ; Neurites ; Amygdala ; Hippocampus ; Apolipoprotein E

Springer Online Journal Archives 1860-2000

Medicine

Abstract It has been suggested that dystrophic neurites in the hippocampal CA2-3 sector are characteristic of diffuse Lewy body disease (DLBD) but not of Parkinson’s disease (PD). We investigated the severity of neuritic change in the CA2-3 sector of the hippocampus and in the periamygdaloid cortex (PAC) in 45 patients with clinically diagnosed and neuropathologically verified PD. Samples from amygdala, hippocampus, entorhinal cortex (ERC) and cortical gyri were examined for Alzheimer-type (AD) changes and Lewy bodies (LBs) using antibodies against ubiquitin and tau. Ubiquitin-positive but polyclonal tau-negative neurites were detected in the CA2-3 region of the hippocampus in 88% of patients and in the PAC in 91% of patients. The CA2-3 sector neurites correlated significantly only with LBs in all other brain areas, except in the amygdala. The neurites in the PAC correlated significantly with neuropathological variables in all other brain areas examined, except with tangles in the precentral and frontal gyrus and with LBs in the amygdala and in the ERC. Unlike in the CA2-3 sector, the neuritic change in the PAC was more prominent in those PD patients with more severe cognitive impairment (P = 0.03). There was no significant correlation between the apoɛ4 allele load and the neuritic change in the PAC or in the CA2-3 sector. Our study revealed that cortical LBs and neuritic change in the amygdala and hippocampal CA2-3 sector co-exist in PD. Unlike hippocampal neurites, the PAC neurites are related to AD pathology. There seems to be a relationship between the PAC neurites and cognitive impairment in PD, but its significance needs further elucidation.

Electronic Resource

1432-0533

Key words Apolipoprotein E ; Genotype ; Parkinson’s ; disease ; Alzheimer’s disease ; Polymerase chain reaction

Springer Online Journal Archives 1860-2000

Medicine

Abstract We determined the apolipoprotein E (apoE) genotype in clinically diagnosed and neuropathologically verified cases of Parkinson’s disease (PD) (n = 45), with or without Alzheimer (AD)-type changes, and compared the apoE genotype with that in healthy age-matched controls (n = 59). The PD cases were divided into two groups according to the CERAD criteria: “O + A”, with no or only uncertain histological findings of AD, and “B + C” with histological findings suggestive or indicative of AD. DNA was isolated from frozen brain samples, and the apoE genotypes were determined using polymerase chain reaction amplification and subsequent restriction analysis by HhaI enzyme. The frequency of the apoɛ4 allele (29.4%) was significantly increased in the B + C group. The odds ratio for an apoɛ4 allele in the B + C group was 2.5 as compared to controls (95% confidence interval, 1.2–5.2). In the 0 + A group, the frequency of apoɛ4 allele (13.6%) was similar to that in controls (14.4%) and the risk of an apoɛ4 allele was not increased (odds ratio 0.94). The PD cases with an apoɛ4 allele had a greater number of cortical (P = 0.02) but not nigral Lewy bodies than those without an apoɛ4 allele (P = 0.57). The results show that neuropathologically verified PD as such is not associated with increased apoɛ4 allele frequency.

Electronic Resource

1432-0533

Key words Alzheimer-type changes ; Cortical Lewy bodies ; Ubiquitin ; Parkinson’s disease ; Dementia

Springer Online Journal Archives 1860-2000

Medicine

Abstract We investigated the role of cortical Lewy bodies (LB) and Alzheimer-type changes in cognitive impairment in patients with idiopathic Parkinson’s disease (PD). We evaluated 44 cases for the extent of neuropathological lesions with a CERAD neuropathological assessment battery and the stage of dementia using Reisberg’s global deterioration scale (GDS). Substantia nigra, amygdala, hippocampus and cerebral cortex were examined for LB and Alzheimer-type changes. For detection of LB, the cortical areas were stained with polyclonal antibodies against ubiquitin and tau. We found at least one cortical LB in 93% of cases. Furthermore, 43% of the cases had histological findings of definite Alzheimer’s disease (AD). The association between cognitive impairment and the number of cortical LB and Alzheimer-type changes in the amygdala, hippocampus and six selected gyri from cerebral cortex were analyzed using stepwise linear regression. In this analysis the total number of cortical LB, and the amount of neurofibrillary tangles in the temporal cortex remained statistically significant. When the cases with neuropathological changes consistent with a diagnosis of AD were excluded, the correlation between the total number of cortical LB and cognitive impairment was more obvious. A stepwise linear regression analysis in these cases found the total number of cortical LB to be the statistically significant predictor of cognitive impairment. This study revealed that LB densities in the cortex, especially in the temporal neocortex, correlated significantly with the cognitive impairment in PD independent of or in addition to Alzheimer-type pathology.

Electronic Resource

1432-0533

Key words Alpha-synuclein ; Cortical Lewy bodies ; Cognitive impairment ; Parkinson’s disease

Springer Online Journal Archives 1860-2000

Medicine

Abstract Amygdala, hippocampus and six cortical gyri were examined for the Lewy body (LB) degeneration and Alzheimer’s disease (AD) type changes in 45 patients with Parkinson’s disease (PD). For detection of LBs, the brain areas were stained with an antibody against alpha-synuclein. The extent of neuropathological lesions was investigated in relation to cognitive dysfunction and apolipoprotein E (apoE) ɛ4 allele dosage. At least one cortical LB was found in 95% of cases (43/45). Furthermore, 40% of cases (18/45) had histological findings of definite AD (CERAD class C). Those PD cases with the apoE ɛ4 allele had a significantly greater number of cortical LBs than those without the apoE ɛ4 allele, but this was statistically significant only in precentral, angular and temporal gyri. The LB density correlated better with the number of plaques than with the density of tangles. The number of LBs in several cortical areas correlated significantly with the cognitive impairment. In stepwise linear regression analysis, the number of LBs in the cingulate gyrus and the amount of tangles in the temporal cortex remained statistically significant. When the CERAD class C was excluded, the correlation between cognitive decline and the number of LBs in cortical areas became even more pronounced. A stepwise linear regression analysis in these cases found the number of LBs in the frontal gyrus to be the statistically most significant predictor of cognitive impairment. This study shows, for the first time, that in PD, alpha-synuclein-positive cortical LBs are associated with cognitive impairment independent of AD-type pathology.

Electronic Resource

1432-1459

Key Words Fluorodopa ; Heredity ; Parkinson’s disease ; PET ; Twins

Springer Online Journal Archives 1860-2000

Medicine

Abstract Positron emission tomography (PET) studies were carried out with [18F]6-fluorodopa ([18F]6-FD) in monozygotic (MZ) and dizygotic (DZ) twins for the clarification of dopaminergic function. Four MZ and four DZ pairs of twins, each pair consisting of a parkinsonian index case and an asymptomatic co-twin, were collected from the Nationwide Twin Cohort. The control group comprised 14 healthy volunteers. [18F]6-FD PET examinations with a Siemens/CTI 931/08 scanner were performed dynamically over 90 min. The regions-of-interest analysis included the caudate, the putamen and the occipital reference regions. Patlak plots were calculated using occipital tissue input function. The accumulation of [18F]6-FD in the putamen of the asymptomatic co-twins was significantly lower than that in the normal subjects. This result implies that there may be a preclinical stage of Parkinson’s disease in the apparently normal co-twins at the time of the PET study.

Electronic Resource

1435-1463

Brain stem ; caudate/putamen ; cortex ; dopamine ; dopamine D1 and D2 receptors ; monoamine uptake inhibitors ; norepinephrine ; serotonin

Springer Online Journal Archives 1860-2000

Medicine

Summary Rats were treated with desipramine 5mg/kg, nomifensine 10mg/kg, zimelidine 25 mg/kg or with 0.9% sodium chloride once a day during the second and third weeks after birth, and brain stem, caudate/putamen and cortical monoamines, and caudate/putamen dopamine D1 (3[H]SCH 23390) and D2 (3[H]spiroperidol) receptor binding were measured when rats were at two months of age. In the brain stem, the concentration of 3-methoxy-4-hydroxy-phenyl glycol was increased in nomifensine rats and the ratio of 5-hydroxyindoleacetic acid to 5-hydroxytryptamine was increased in zimelidine rats. In the caudate/putamen, the concentrations of 3,4-dihydroxyphenylacetic acid and homovanillic acid and the ratio of homovanillic acid to dopamine were increased in desipramine rats; neither3[H]SCH 23390 nor3[H]spiroperidol binding were affected by any of the three monoamine uptake inhibiting antidepressants studied. In the cortex, the ratio of 5-hydroxyindoleacetic acid to 5-hydroxytryptamine was increased in desipramine and zimelidine rats. The findings suggest that desipramine but not nomifensine increases the metabolism of dopamine in the caudate/ putamen and nomifensine but not desipramine increases the metabolism of norepinephrine in the brain stem, and furthermore that the metabolism of serotonin is affected by desipramine as well as by zimelidine. It is possible that also treatment of women with these drugs during late pregnancy causes long-lasting changes in the brain of human fetus.

Electronic Resource

1435-1463

Herpes simplex virus ; autoreceptors ; dopamine ; rotational behaviour ; experimental encephalitis ; D-2 receptors ; D-1 receptors

Springer Online Journal Archives 1860-2000

Medicine

Summary Brain dopamine receptors were determined in experimental herpes encephalitis using an animal model, where herpes simplex virus type 1 was inoculated onto the cornea of rabbits. The animals exhibit an asymmetric posture and circling to the side of inoculation, which appears to be connected to the altered dopamine transmission in the mesostriatal system. In this study striatal and mesencephalic D-1 and D-2 dopamine receptors were measured by radioligand techniques using3H-SCH 23390 and3H-spiroperidol as ligands. In the striatal D-1 and D-2 receptors there were no significant differences between HSV-inoculated and control rabbits. In the substantia nigra-ventral tegmental area there was a significant decrease in the D-2 receptors (Bmax) on the side contralateral to the primary virus inoculation and the direction of the rotational behaviour, without any changes in the D-1 receptors. Thus experimental herpes simplex virus infection seems to affect the mesencephalic dopamine autoreceptors, leading to unilateral activation of the mesostriatal dopamine system and rotational behaviour.

Electronic Resource

1435-1463

Entacapone ; catechol-O-methyltransferase ; [18F]fluorodopa ; positron emission tomography (PET) ; Parkinson's disease

Springer Online Journal Archives 1860-2000

Medicine

Summary The effect of peripheral catechol-O-methyltransferase (COMT) inhibition with entacapone on striatal uptake of 6-[18F]fluoro-L-dopa (FDOPA) was studied with PET both without and with entacapone in fifteen advanced parkinsonian patients and six healthy controls. Entacapone significantly enhanced the fraction of unmetabolized FDOPA in plasma from 16% to about 50% at 80 minutes after FDOPA injection in all subjects. The striatal to occipital ratios and the striatal FDOPA uptake, expressed as a modified decarboxylation coefficient (k3R0), was significantly increased in healthy controls, whereas in parkinsonian patients the increase was significant only in the caudate. On the other hand, the influx constant (Ki) decreased significantly in the caudate and putamen in parkinsonian patients; in healthy controls the Ki remained virtually unchanged. Effective peripheral COMT inhibition markedly increased the fraction of FDOPA in plasma and thus its availability in the brain for decarboxylation both in patients and control subjects. However, the change in striatal FDOPA uptake was modest in the advanced parkinsonian patients as compared to that in control subjects, because of the advanced disease, decreased storage capacity, or both.

Electronic Resource

1435-1463

Herpes simplex virus ; experimental encephalitis ; monoamines ; dopamine ; rotational behaviour ; latent HSV ; chronic viral infection ; D-2 receptors

Springer Online Journal Archives 1860-2000

Medicine

Summary In this study we have examined brain concentrations of monoamine neurotransmitters and striatal and mesencephalic D-2 receptors in a chronic model of herpes simplex virus (HSV) encephalitis. The HSV-inoculated rabbits were killed two months after inoculation. Dopamine (DA), noradrenaline, serotonin and their metabolites were determined in the substantia nigra, caudate nucleus, putamen, nucleus accumbens, and olfactory tubercles using HPLC with electrochemical detection. The Bmax and Kd values of D-2 receptors were studied in the striatum and in the mesencephalon using3H-spiroperidol as ligand. The animals showed rotational behaviour, consisting of posture tilting to the inoculated side and circling in the same direction during the first week, then slowly subsiding. Compared with controls, the concentration of homovanillic acid (HVA) was reduced in the ascending DA system on both sides. Neither in the number nor affinity of D-2 receptors were there any differences between the HSV-inoculated and control rabbits. The decreased HVA concentrations suggest that dopaminergic hypofunction can develop as a consequence of previously experienced acute HSV brain infection.

Electronic Resource