Reiji Iizuka

Changes of biogenic amines and their metabolites in postmortem brains from patients with Alzheimer-type dementia

Abstract: Noradrenaline (NA), 3,4‐dihydroxyphenyl‐ethylamine (dopamine, DA), 5‐hydroxytryptamine (serotonin, 5‐HT), homovanillic acid (HVA), and 5‐hydroxy‐indoleacetic acid (5‐HIAA) were measured in 22 regions of postmortem brains from four histologically verified cases with Alzheimer‐type dementia (AID) and nine histologically normal controls. Compared with the controls, concentrations of 5‐HT and 5‐HIAA in the ATD brains were significantly reduced in nine regions (superior frontal gyrus, insula, cingulate gyrus, amygdala, putamen, medial and lateral segments of globus pallidus, substantia nigra, lateral nucleus of thalamus) and in eight regions (amygdala, substantia innominata, caudate, putamen, medial and lateral segments of globus pallidus, medial and lateral nuclei of thalamus), respectively. NA concentrations of the ATD brains were significantly reduced in six regions (cingulate gyrus, substantia innominata, putamen, hypothalamus, medial nucleus of thalamus, raphe area). In contrast, significant reductions of DA and HVA concentrations in the ATD brains were found only in putamen and amygdala, respectively. The 5‐HIAA/5‐HT ratio in the ATD brains decreased significantly in locus coeruleus, while the HYA/DA ratio increased significantly in putamen and medial segment of globus pallidus. These findings suggest that the serotonergic and noradrenergic systems are affected, while the dopaminergic system is relatively unaffected in ATD brains.

Biopterin in human brain and urine from controls and parkinsonian patients: Application of a new radioimmunoassay

Total biopterin concentrations in the post-mortem human brain (caudate nucleus) and in the urine of controls and parkinsonian patients were measured by a newly developed radioimmunoassay. There was good correlation between the total biopterin level and tyrosine hydroxylase activity in the human brain. Biopterin concentrations in the caudate nucleus were greatly reduced in parkinsonian patients. In contrast, the reduction of urinary biopterin in parkinsonian patients was slight and not statistically significant, as compared with normal controls.

Phenylethanolamine N-methyltransferase and other enzymes of catecholamine metabolism in human brain

The activities of tyrosine hydroxylase (TH), DOPA decarboxylase (DDC), dopamine beta-hydroxylase (DBH), phenylethanolamine N-methyltransferase (PNMT), and monoamine oxidase (MAO) with serotonin and phenylethylamine as substrates were measured in catecholaminergic regions of human brain from 10 controls and 3 patients with Parkinsonism. PNMT activity was detected in hypothalamus, thalamus and cerebellar nucleus of the control human brain, and was reduced in hypothalamus of Parkinsonian cases. Type A (with serotonin as substrate) and type B (with phenylethylamine as substrate) MAO activities were high in all brain regions with little individual variations in controls and Parkinsonian cases. TH activity was high in the controls and was markedly decreased, in substantia nigra, caudate nucleus, putamen and in pallidum, in all three cases of Parkinsonism. DDC activity in these regions was also decreased in 2 patients. However, one Parkinsonian case had only decreased TH and normal DDC activities. DBH activity in hypothalamus was also reduced in the Parkinsonian cases.

Morphological and biochemical changes in the cholinergic and monoaminergic systems in Alzheimer-type dementia

SummaryThe integrity of cholinergic and monoaminergic neuronal systems in Alzheimer-type dementia (ATD) was studied using a combination of morphological and biochemical procedures applied to samples from seven ATD brains and ten control brains. On morphological examination, the number of neurons was counted in the nucleus basalis of Meynert (nbM), the locus coeruleus (LC) and the nucleus centralis superior (NCS). Biochemically, the activities of choline acetyltransferase (ChAT) and the concentrations of noradrenaline (NA) and serotonin (5-hydroxytryptamine; 5-HT) were measured in the nbM, LC, NCS, frontal cortex, temporal cortex and occipital cortex. Compared with the controls, the mean number of neurons in the nbM and LC were significantly reduced in the ATD brains. The neuronal loss in the NCS in the ATD brains was not significant. The ChAT activities in all regions from the ATD brains had a tendency to be reduced. Marked reductions in the NA concentrations in the LC and 5-HT concentrations in the temporal and occipital cortices were found in the ATD brains. These findings suggest that various neurotransmitter systems, including cholinergic, noradrenergic and serotonergic systems, are affected in the ATD brains.

Calbindin-immunoreactive cholinergic neurones in the nucleus basalis of Meynert in Alzheimer-type dementia

An antibody to the calcium binding protein, calbindin D28K (CaBP), was used to study the number and size of CaBP-immunoreactive neurones in the nucleus basalis of Meynert (nbM) of postmortem human brains from neurologically normal controls and from patients with neuropathologically diagnosed Alzheimer-type dementia (ATD). In controls, almost all the large neurones and their processes in the nbM were CaBP immunoreactive. Compared to neurologically normal controls the number of CaBP-immunoreactive neurones in the nbM in patients dying with ATD was significantly reduced and there was a clear loss of the majority of CaBP immunoreactive neurones. The few remaining nbM CaBP immunoreactive neurones in the ATD cases were smaller than those in the neurologically normal controls. Double-staining experiments revealed that many of the nbM CaBP-immunoreactive neurones contained choline acetyltransferase immunoreactivity, so that CaBP is an alternative marker for the nbM cholinergic neurones in the human fore-brain. These findings suggest that a disturbance in calcium homeostasis may be a possible factor contributing to the loss of these cholinergic/CaBP-containing neurones.

A preliminary study of free amino acids in the postmorten temporal cortex from Alzheimer-type dementia patients

Concentrations of free amino acids were measured in the temporal cortex of postmortem brains from four histologically verified cases with Alzheimer-type dementia (ATD) and eight histologically normal controls. The concentrations of taurine, glutamate, and gamma-aminobutyric acid, which are all neurotransmitter candidates, were significantly lower in the ATD brains than in the controls. These findings suggest that the involvement of amino acid neurons in ATD cannot be ruled out.

Extrahypophyseal distribution of α-melanocyte stimulating hormone (α-MSH)-like immunoreactivity in postmortem brains from normal subjects and Alzheimer-type dementia patients

Abstract Using a sensitive double-antibody solid-phase enzyme immunoassay method α-melanocyte stimulating hormone-like immunoreactivity (α-MSH-LI) was measured in 21 regions of postmortem brains from 8 normal subjects and 5 patients with Alzheimer-type dementia (ATD). In the brains from the normal subjects, the highest concentration of α-MSH-LI was found in the hypothalamus. Relatively high concentration were also measured in the locus coeruleus, substantia innominata, substantia nigra, amygdala and medial nucleus of thalamus. α-MSH-LI in other regions was approximately1/100 of the hypothalamic content. This data is consistent with the existence of α-MSH in extrahypophyseal regions and indicates its regional distribution in the human brain. In the Alzheimer brains, although the temporal cortex and hippocampus had normal concentrations of α-MSH-LI, the cingulate cortex, caudate and substantia nigra showed significantly lower concentrations of α-MSH-LI than those of the control brains. This data suggests that further studies of α-MSH content in a larger number of ATD brains would be useful.

Age- and sex-related differences in the nerve growth factor distribution in the rat brain.

Levels of the nerve growth factor (NGF) have been measured in various brain regions of young and aged male and female rats of Wistar strain by means of a highly sensitive two-site enzyme immunoassay system for beta-NGF. Among the ten regions examined, the amount of NGF per wet weight of tissue was found to be highest in the hippocampus, irrespective of the sex and age. The NGF concentration in the hippocampus of female rats at 3 months of age was comparable to that of same aged males. Further, there was no significant difference in the NGF levels of the hippocampus between young and age males. However, the NGF level was significantly lower in aged females as compared to that in 3- or 4-month-old females, and hence the marked male-female difference was found in the NGF levels in aged Wistar rats.

Dopamine-stimulated adenylate cyclase activity in the human brain: Changes in Parkinsonism

Abstract Basal adenylate cyclase activity in the caudate nucleus was found to be present in frozen postmortem human caudate nuclei both in normal controls and in Parkinsonian patients. Although the activity of dopamine-stimulated adenylate cyclase in human brain was low, significantly higher stimulation of adenylate cyclase activity by dopamine was observed in the caudate nuclei of Parkinsonian patients than in those of normal controls.

Tryptophan hydroxylase activity in the brains of controls and parkinsonian patients

The activity of tryptophan hydroxylase was measured in nine regions of human brains from controls and patients with Parkinsons disease, striato-nigral degeneration, Shy-Drager syndrome and progressive supranuclear palsy by high performance liquid chromatography with fluorescence detection. The regional distribution of the enzyme activity in control brains was similar to that of serotonergic neurons; relatively high activity was found in the raphe nucleus, locus coeruleus and substantia nigra. The activity in the thalamus in Parkinsons disease and that in the locus coeruleus, raphe nucleus and substantia nigra in striato-nigral degeneration were significantly lower than that of controls (p<0.05). In most other brain regions in parkinsonian patients the activity was relatively lower than that of controls except the caudate nucleus and nucleus accumbens where the activity was relatively higher than that of controls. Marked decrease in the enzyme activity in various brain regions was observed in striato-nigral degeneration, Shy-Drager syndrome, and progressive supranuclear palsy. These results suggest that the activity of tryptophan hydroxylase in serotonergic neurons is reduced in the brains of parkinsonian patients and of patients with degenerative nervous diseases.