Differential Changes in the Content of Amino Acid Neurotransmitters in Discrete Regions of the Rat Brain Prior to the Onset and During the Course of Homocysteine-Induced Seizures

Changes in amino acid concentrations were investigated in selected regions of rat brain prior to the onset and during the course of epileptiform seizures induced by L-homocysteine. The concentration of gamma-aminobutyric acid (GABA) decreased preictally in substantia nigra (-18%), caudate putamen (-26%), and inferior colliculus (-46%). After seizure onset, the GABA content was further reduced in substantia nigra (-31%) and additionally in hippocampus (-18%). Preictal taurine levels were elevated in globus pallidus (+26%) and caudate putamen (+13%) but returned to normal after seizure onset. However, in hippocampus, taurine decreased both preictally (-22%) and after seizure onset (-56%). Glycine was reduced preictally only in globus pallidus (-13%). After seizure onset the direction of its concentration change varied in the brain regions studied. Glutamate levels decreased preictally in hippocampus (-10%) and hypothalamus (-46%) but increased in globus pallidus (+14%). Normal levels were detectable after seizure onset in hypothalamus and globus pallidus but a further reduction in hippocampus (-59%) and significant reductions in substantia nigra (-15%) and caudate putamen (-17%) were detected. Aspartate was elevated in hippocampus, both preictally (+49%) and after seizure onset (+21%) while at the same phases in globus pallidus a consistent reduction (-30%) was observed. The glutamine content increased preictally in globus pallidus (+41%) and hypothalamus (+36%), and in all brain areas during the ictal phase of seizure, the hippocampus exhibiting a dramatic increase (approximately 300%). The contents of serine and alanine were altered in most regions studied only after seizure onset, with the exception of the hippocampus, where a decrease (-41%) of serine was observed preictally.     

Transferrin and Iron in Normal, Alzheimer's Disease, and Parkinson's Disease Brain Regions

Abstract: Oxidant-mediated damage is suspected to be involved in the pathogenesis of several neurodegenerative disorders. Iron promotes conversion of hydrogen peroxide to hydroxyl radical and, thus, may contribute to oxidant stress. We measured iron and its transport protein transferrin in caudate, putamen, globus pallidus, substantia nigra, and frontal cortex of subjects with Alzheimer's disease (n = 14) and Parkinson's disease (n = 14), and in younger adult (n = 8) and elderly (n = 8) normal controls. Although there were no differences between control groups with regard to concentrations of iron and transferrin, iron was significantly increased ( p < 0.05) in Alzheimer's disease globus pallidus and frontal cortex and Parkinson's disease globus pallidus, and transferrin was significantly increased in Alzheimer's disease frontal cortex, compared with elderly controls. The transferrin/iron ratio, a measure of iron mobilization capacity, was decreased in globus pallidus and caudate in both disorders. Regional transferrin and iron concentrations were generally more highly correlated (Pearson's correlation coefficient) in elderly controls than in Alzheimer's and Parkinson's disease. The altered relationship between iron and transferrin provides further evidence that a disturbance in iron metabolism may be involved in both disorders.     

Decreased Proline Endopeptidase Activity in the Basal Ganglia in Huntington''s Disease

Soluble proline endopeptidase (EC 3.4.21.26) activity was measured by a fluorometric assay in eight human brain areas (caudate nucleus, lateral globus pallidus, medial globus pallidus, substantia nigra-zona compacta, substantia nigra-zona reticulata, frontal cortex-Brodmann area 10, temporal cortex-Brodmann area 38, and hippocampus), in 10 control and 10 Huntington's disease brains. An abnormally low activity (22% of control activity) was found in the caudate nucleus of Huntington's disease brains; significantly decreased activity was also detected in the lateral globus pallidus and medial globus pallidus (37% and 40% of control, respectively).     

MRI evaluation of basal ganglia ferritin iron and neurotoxicity in Alzheimer's and Huntingon's disease.

BACKGROUND: The basal ganglia contain the highest levels of iron in the brain and post-mortem studies indicate a disruption of iron metabolism in the basal ganglia of patients with neurodegenerative disorders such as Alzheimer's disease (AD) and Huntington's disease (HD). Iron can catalyze free radical reactions and may contribute to oxidative damage observed in AD and HD brain. Magnetic resonance imaging (MRI) can quantify transverse relaxation rates, which can be used to quantify tissue iron stores as well as evaluate increases in MR-visible water (an indicator of tissue damage). METHODS: A magnetic resonance imaging (MRI) method termed the field dependent relaxation rate increase (FDRI) was employed which quantifies the iron content of ferritin molecules (ferritin iron) with specificity through the combined use of high and low field-strength MRI instruments. Three basal ganglia structures (caudate, putamen and globus pallidus) and one comparison region (frontal lobe white matter) were evaluated. Thirty-one patients with AD and a group of 68 older control subjects, and 11 patients with HD and a group of 27 adult controls participated (4 subjects overlap between AD and HD controls). RESULTS: Compared to their respective normal control groups, increases in basal ganglia FDRI levels were seen in both AD and HD. FDRI levels were significantly increased in the caudate (p = 0.007) and putamen (p = 0.008) of patients with AD with a trend toward an increase in the globus pallidus (p = 0.13). In the patients with HD, all three basal ganglia regions showed highly significant FDRI increases (p<0.001) and the magnitude of the increases were 2 to 3 times larger than those observed in AD versus control group comparison. For both HD andAD subjects, the basal ganglia FDRI increase was not a generalized phenomenon, as frontal lobe white matter FDRI levels were decreased in HD (p = 0.015) and remained unchanged in AD. Significant low field relaxation rate decreases (suggestive of increased MR-visible water and indicative of tissue damage) were seen in the frontal lobe white matter of both HD and AD but only the HD basal ganglia showed such decreases. CONCLUSIONS: The data suggest that basal ganglia ferritin iron is increased in HD and AD. Furthermore, the increased iron levels do not appear to be a byproduct of the illness itself since they seem to be present at the onset of the diseases, and thus may be considered a putative risk factor. Published post-mortem studies suggest that the increase in basal ganglia ferritin iron may occur through different mechanisms in HD and AD. Consistent with the known severe basal ganglia damage, only HD basal ganglia demonstrated significant decreases in low field relaxation rates. MRI can be used to dissect differences in tissue characteristics, such as ferritin iron and MR-visible water, and thus could help clarify neuropathologic processes in vivo. Interventions aimed at decreasing brain iron levels, as well as reducing the oxidative stress associated with increased iron levels, may offer novel ways to delay the rate of progression and possibly defer the onset of AD and HD.     

Effect of stimulation of the caudate nucleus on activity of neurons of the globus pallidus

Activity of neurons of the globus pallidus was recorded extracellularly during stimulation of the caudate nucleus. It is demonstrated that background activity (BA) of most neurons of the globus pallidus is depressed under these conditions, which is regarded as a manifestation of inhibition of the investigated neurons. The period of BA depression varied in different cells from 60 to 500 msec. In some cases this period was preceded by emergence of an action potential with a latent period of 10–20 msec. In addition to inhibition of the activity of globus pallidus neurons during stimulation of the caudate nucleus, it was possible to record evoked responses of the given neurons in the form of group discharges with a latent period of 18–40 msec and single action potentials with a latent period of 50–100 msec. The neurons that reacted with a shorter latent period were localized at the lateral limit of the globus pallidus, whereas neurons with other kinds of responses were distributed in the globus pallidus comparatively evenly.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 1, No. 2, pp. 202–209, September–October, 1969.     

Evidence for a novel pituitary protein (7B2) in human brain, cerebrospinal fluid and plasma: brain concentrations in controls and patients with Alzheimer's disease

A novel pituitary protein, designated as 7B2, recently purified in our laboratory was measured using a specific radioimmunoassay in conjunction with immuno-affinity extraction, in cerebrospinal fluid (CSF) and in plasma obtained from normal volunteers. The mean concentrations of immunoreactive (IR)-7B2 were 2154 pg/ml in CSF and 29 pg/ml in plasma. Studies by SDS-poly-acrylamide gel electrophoresis revealed that both CSF IR-7B2 and plasma IR-7B2 have an apparent molecular weight of around 20,000-21,000 as previously observed in various rat tissues. IR-7B2 was also measured in various brain regions obtained from control subjects and patients with Alzheimer's disease. IR-7B2 was widely distributed in the human brain, with the highest concentrations in substantia nigra and caudate. IR-7B2 brain concentrations were found to be similar between control subjects and patients with Alzheimer's disease. Gel permeation chromatography of extracts of various brain regions revealed two major peaks with apparent molecular weights of 45,000-50,000 and 11,000-16,000 in hypothalamus, caudate, frontal cortex, hippocampus, putamen and locus coeruleus, and only one peak with an apparent molecular weight of 14,000-16,000 in substantia nigra and globus pallidus. These data suggest that this novel pituitary protein may play a role of consequence perhaps as a neurotransmitter or as a neuromodulator in the human central nervous system.     

Globus pallidus: a target brain region for divalent metal accumulation associated with dietary iron deficiency

Recently, iron deficiency has been connected with a heterogeneous accumulation of manganese in the rat brain. The striatum is particularly vulnerable, for there is a significant negative correlation between accumulated manganese and gamma-aminobutyric acid levels. The effect of dietary iron deficiency on the distribution of zinc and copper, two other divalent metals with essential neurobiological roles, is relatively unexplored. Thus, the primary goal of this study was to examine the effect of manipulating dietary iron and manganese levels on the concentrations of copper, iron, manganese and zinc in five rat brain regions as determined with inductively coupled plasma mass spectrometry analysis. Because divalent metal transporter has been implicated as a transporter of brain iron, manganese, and to a lesser extent zinc and copper, another goal of the study was to measure brain regional changes in transporter levels using Western blot analysis. As expected, there was a significant effect of iron deficiency (P < 0.05) on decreasing iron concentrations in the cerebellum and caudate putamen; and increasing manganese concentrations in caudate putamen, globus pallidus and substantia nigra. Furthermore, there was a significant effect of iron deficiency (P < 0.05) on increasing zinc concentration and a statistical trend (P = 0.08) toward iron deficiency-induced copper accumulation in the globus pallidus. Transporter protein in all five regions increased due to iron deficiency compared to control levels (P < 0.05); however, the globus pallidus and substantia nigra revealed the greatest increase. Therefore, the globus pallidus appears to be a target for divalent metal accumulation that is associated with dietary iron deficiency, potentially caused by increased transporter protein levels.     

A Quantitative Analysis of Isoferritins in Select Regions of Aged, Parkinsonian, and Alzheimer's Diseased Brains

Abstract: The brain requires a ready supply of iron for normal neurological function, but free iron is toxic. Consequently, iron bioavailability must be stringently regulated. Recent evidence has suggested that the brain iron regulatory system is dysfunctional in neurological disorders such as Alzheimer's and Parkinson's diseases (AD and PD, respectively). A key component of the iron regulatory system in the brain is ferritin. Ferritin consists of 24 subunits, which are distinguished as either a heavy-chain (H) or light-chain (L) isoform. These peptide subunits are genetically and functionally distinct. Thus, the ability to investigate separately the types of ferritin in brain should provide insight into iron management at both the cellular and the molecular level. In this study, the ratio of isoferritins was determined in select regions of adult elderly AD and PD human brains. The H-rich ferritin was more abundant in the young brain, except in the globus pallidus where the ratio of H/L ferritin was 1:1. The balance of H/L isoferritins was influenced by age, brain region, and disease state. With normal aging, both H and L ferritin increased; however, the age-associated increase in isoferritins generally failed to occur in AD and PD brain tissue. The imbalance in H/L isoferritins was disease and region specific. For example, in frontal cortex, there was a dramatic (fivefold) increase in the ratio of H/L ferritin in AD brains but not in PD brains. In PD, caudate and putamen H/L ratios were higher than in AD and the elderly control group. The analysis of isoferritin expression in brain provides insight into regional iron regulation under normal conditions and suggests a loss of ability to maintain iron homeostasis in the two disease states. This latter observation provides further evidence of dysfunction of iron homeostatic mechanisms in AD and PD and may contribute significantly to understanding the underlying pathogenesis of each, particularly in relation to iron-induced oxidative damage.     

Monoamine Oxidase Activity and Monoamine Metabolism in Brains of Parkinsonian Patients Treated with l-Deprenyl

Monoamine oxidase (MAO) type A and type B were measured using kynuramine, 3,4-dihydroxyphenylethylamine (dopamine, DA), and 5-hydroxytryptamine (5-HT, serotonin) in 20 brain areas. The highest activities were found in the striatum (caudate nucleus, putamen, globus pallidus, and substantia nigra), hypothalamus, and c-mammilare. The ratio of DA to 5-HT deamination varied in the different regions, being in favor of DA in the striatum. With kynuramine as the substrate IC50 values of a number of inhibitors indicated that l-deprenyl was far more potent an inhibitor of human brain MAO than clorgyline or harmaline. N-Desmethylpropargylindane hydrochloride (AGN 1135) was also shown to have MAO-B inhibitory selectivity similar to that of l-deprenyl. Brains obtained at autopsy from l-deprenyl-treated Parkinsonian patients showed that, whereas MAO-B was fully inhibited by the therapeutic doses of l-deprenyl, substantial MAO-A activity was still evident. These results are matched by the significant increases of DA noted in caudate nucleus, globus pallidus, putamen, and substantia nigra and the unaltered 5-HT and 5-hydroxyindoleacetic acid (5-HIAA) in the same regions. These data indicate that the therapeutic actions of l-deprenyl may lie in its selective inhibition of MAO-B resulting in increased brain levels of DA formed from L-dihydroxyphenylacetic acid (L-DOPA).     

Neuroprotection by bioactive components in medicinal and food plant extracts

Neurodegenerative diseases of the human brain comprise a variety of disorders that affect an increasing percentage of the population. Some of these are age dependent (e.g. Alzheimer's and Parkinson's diseases) and some are infection dependent, e.g. human immunodeficiency virus (HIV/AIDS). The vulnerable brain regions in HIV/AIDS individuals include the dentate nucleus in the cerebellum, the red nucleus, substantia nigra (SN) in the mid-brain, the subthalamic nucleus, thalamic fasciculus in the diencephalons, the globus pallidus and striatum (or neostriatum, which consists of caudate and putamen) in the forebrain. Lesion in these regions may lead to progressive dementia, which is similar to what is observed in Alzheimer's disease and Parkinson's disease. The entry of calcium into the cytoplasm of cells at concentrations that can activate oxidative enzymes such as phospholipase A(2) and xanthine oxidase, deplete cells of cysteine and glutathione, cause mitochondrial release of free radicals and cell death. Glutamate and its receptors are key molecular elements at the interface between neurons and glia. Dietary factors can modulate physiological functions (including brain function) thereby increasing the economic productivity of a population as a function of health. A greater understanding of the molecular mechanisms of neuroprotection, oxidative stress and immune function will facilitate definition of the prophylactic potentials of diet, nutritional/food supplements, medicinal plants and herbal extracts.     

Differential Regional Effects of Methamphetamine on the Activities of Tryptophan and Tyrosine Hydroxylase

Abstract : Administration of high doses of methamphetamine (METH) produces both short- and long-term enzymatic deficits in central monoaminergic systems. To determine whether a correlative relationship exists between these acute and long-term consequences of METH treatment, in the present study we examined the regional effects of METH on tryptophan hydroxylase (TPH) and tyrosine hydroxylase (TH) activities in various regions of the caudate nucleus, nucleus accumbens, and globus pallidus. A single METH administration decreased TPH activity 1 h after treatment in the globus pallidus, in the nucleus accumbens, and throughout the caudate ; in the anterior caudate, the ventral-medial was more affected than the dorsal-lateral region. In contrast, TH activity was not decreased in either the caudate or the globus pallidus after a single METH administration ; however, it was altered in the nucleus accumbens. Seven days after multiple METH administrations, TH and TPH activities were decreased in most caudate regions but not in the nucleus accumbens or globus pallidus. These data demonstrate that (1) the effects of METH on TPH and TH vary regionally ; and (2) the short-term and long-term regional responses of TPH to METH in the caudate and globus pallidus correlated. In contrast, METH-induced acute TH responses did not predict the long-term changes in TH activity.     

Monoamine neurotransmitters and their metabolites in brain regions in alzheimer's disease: A postmortem study

1. Concentrations of the neurotransmitter amines noradrenaline (NA), dopamine (DA), and 5-hydroxytryptamine (5-HT) and the acid metabolites homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA) were determined in four regions of postmortem brains of demented patients with or without Alzheimer's disease (AD). 2. NA was deficient in the temporal cortex (BA 21) of AD, but not of non-AD, patients. 3. Caudate, in particular, had an impaired dopaminergic system in AD patients, with low HVA levels. 4. In all regions investigated [amygdala, caudate, putamen, temporal cortex (BA 21)] 5-HT was significantly depleted in AD patients, and 5-HIAA was also depleted in amygdala and caudate. 5. These results indicate that neurotransmitter systems other than cholinergic systems are also widely affected in AD and suggest that these deficits may also play an important role in determining the symptomatology of AD.     

Asymmetry of basal ganglia in children with attention deficit hyperactivity disorder

Attention deficit hyperactivity disorder (ADHD) is a common neuropsychiatry disorder with several key symptoms, such as inattentiveness, impulsivity and hyperactivity. Neuropsychiatry studies have implicated the frontostriatal circuit in the pathological physiology of the disorder. Using magnetic resonance imaging (MRI), we examined the basal ganglia in 13 ADHD patients and eight unaffected comparison children. The volume of caudate, putamen and globus pallidus was measured. In the ADHD patients, we detected an increased left > right asymmetry of the basal ganglia. This reversal of asymmetry in the globus pallidus and caudate nucleus were statistically significant. These finding provide further evidence of morphological brain abnormalities in ADHD.     

Thiamine, Thiamine Phosphates, and Their Metabolizing Enzymes in Human Brain

Abstract: Total thiamine (the sum of thiamine and its phosphate esters) concentrations are two- to fourfold lower in human brain than in the brain of other mammals. There were no differences in the total thiamine content between biopsied and autopsied human brain, except that in the latter, thiamine triphosphate was undetectable. The main thiamine phosphate-metabolizing enzymes could be detected in autopsied brain, and the kinetic parameters were comparable to those reported in other species. Thiamine diphosphate levels were lowest in hippocampus (15 ± 4 pmol/mg of protein) and highest in mammillary bodies (24 ± 4 pmol/mg of protein). Maximal levels of thiamine and its phosphate ester were found to be present at birth. In parietal cortex and globus pallidus, mean levels of total thiamine in the oldest age group (77–103 years) were, respectively, 21 and 26% lower than those in the middle age group (40–55 years). Unlike cerebral cortex, the globus pallidus showed a sharp drop in thiamine diphosphate levels during infancy, with concentrations in the oldest group being only ∼50% of the levels present during the first 4 months of life. These data, consistent with previous observations conducted in blood, suggest a tendency toward decreased thiamine status in older people.     

Corticotropin-releasing factor in humans. I. CRF stimulation in normals and CRF radioimmunoassay

The biological activity of ovine (o) and human (h) corticotropin-releasing factor (CRF) in normal volunteers was investigated, using bolus injections with different CRF dosages. There was a significant increase of ACTH, beta-endorphin and cortisol after the injection of all dosages. Repetitive stimulation and continuous infusion of hCRF lead to repetitive release of identical amounts of ACTH or constant elevation of ACTH levels. oCRF and hCRF serum immunoreactivity was measured with specific radioimmunoassays after bolus injection, pulsatile administration and infusion of CRF. The half-time of serum disappearance after acute injection studies was calculated as 9 min for hCRF dand 18 min for oCRF. The 'metabolic clearance' of hCRF calculated using the infusion study was 2.72 ml/min X kg. Endogenous CRF immunoreactivity was detectable in 14 patients during insulin hypoglycemia and in 86 out of 97 pregnant females. Furthermore, CRF could be extracted from human placenta. The chromatographic pattern of extracted placenta CRF, pregnancy serum CRF and CRF standard preparation was identical. Furthermore, CRF immunoreactivity was detectable in some patients with different causes of ACTH hypersecretion.     

成年大鼠纹状体、边缘区和苍白球的计算机三维结构重建

应用计算机图形技术在大鼠脑的连续冠状切片Nissl染色的基础上通过Onyx2超级图形工作站对大鼠脑的纹状体进行了三维重建。结果提示：大鼠纹状体由尾壳核、苍白球和边缘区三部分组成,其中边缘区位于尾壳核和苍白球之间,被二完全包绕;尾壳核呈近似的内凹半球形,嘴尾径最大的为6.2mm;背腹径最大为4.9mm;宽度（冠状平面上的内外径)为3.5mm。从嘴侧到尾侧随着脑平面的增宽,尾壳核逐渐向外侧（即靠近外轮廓的方向）移位。苍白球呈块形,嘴尾径最大为4.4mm,背腹径最大为2.6mm,宽度（冠状平面上的内外径）最大为1.5mm。位于尾壳核的内侧,除内侧外基它三个方向均被尾壳核包绕。边缘区呈现一个片状扇形结构,嘴侧背腹径大,最大为2.2mm,宽约0.17mm;尾侧背腹径小,为0.8mm,宽约0.13mm。同属壳核和苍白球一样,从嘴侧到尾侧随着脑平面的增宽边缘区亦逐渐向外侧（即靠近外轮廓的方向）移位,其移位的幅度亦明显大于脑平面增宽的幅度;整个边缘区从嘴侧到尾侧呈均匀变化,其片状逐渐变宽,长度（背腹径）逐渐变小,从而形成一个盘状结构。     

Iron levels in the human brain: A post-mortem study of anatomical region differences and age-related changes

The link between brain iron homeostasis and neurodegenerative disease has been the subject of extensive research. There is increasing evidence of iron accumulation during ageing, and altered iron levels in some specific brain regions in neurodegenerative disease patients have been reported.Using graphite furnace atomic absorption spectrometry after microwave-assisted acid digestion of the samples, iron levels were determined in 14 different areas of the human brain [frontal cortex, superior and middle temporal, caudate nucleus, putamen, globus pallidus, cingulated gyrus, hippocampus, inferior parietal lobule, visual cortex of the occipital lobe, midbrain, pons (locus coeruleus), medulla and cerebellum (dentate nucleus)] of n = 42 adult individuals (71 ± 12 years old, range: 53–101 years old) with no known history or evidence of neurodegenerative, neurological or psychiatric disorders.It was found that the iron distribution in the adult human brain is quite heterogeneous. The highest levels were found in the putamen (mean ± SD, range: 855 ± 295 μg/g, 304–1628 μg/g) and globus pallidus (739 ± 390 μg/g, 225–1870 μg/g), and the lowest levels were observed in the pons (98 ± 43 μg/g, 11–253 μg/g) and medulla (56 ± 25 μg/g, 13–115 μg/g).Globally, iron levels proved to be age-related. The positive correlation between iron levels and age was most significant in the basal ganglia (caudate nucleus, putamen and globus pallidus).Compared with the age-matched control group, altered iron levels were observed in specific brain areas of one Parkinson's disease patient (the basal ganglia) and two Alzheimer's disease patients (the hippocampus).     

Huntington's disease: regional alteration in muscarinic cholinergic receptor binding in human brain.

Huntington's Disease, an autosomal dominant neurological disorder, is characterized by diffuse neuronal degeneration particularly in the basal ganglia and cerebral cortex. The purpose of this study was to examine various discrete regions of choreic and control brains for alterations in muscarinic cholinergic receptor binding and choline acetyltransferase (ChAc) activity. Nine postmortem brains, three from patients with Huntington's Disease and six controls, were dissected into 17 discrete regions. Each regional homogenate was assayed for muscarinic receptor concentration by measuring specific membrane binding of [³H]-QNB, a potent muscarinic antagonist which selectively labels brain muscarinic receptors. Aliquots from each brain region were also assayed for ChAc activity. Of significance was the marked reduction in specific [³H]-QNB receptor binding in the caudate nucleus, putamen and globus pallidus of choreic brain while no significant alterations were detected in other brain regions. Significant decreases in ChAc activity were found in the caudate nucleus, putamen, and globus pallidus with no alterations in ChAc activity in the rest of the brain regions examined. The tissues were chosen such that protein levels were similar in both choreic and normal brain samples. The apparent reduction in the number of muscarinic cholinergic receptors in the choreic brains suggests that treatment with cholinomimetic drugs might be beneficial in Huntington's Disease.     

Regional expression of a MCD-peptide and dendrotoxin I-sensitive voltage-dependent potassium channel in rat brain

In situ hybridization histochemistry has been used to analyze the regional expression of a class of voltage-dependent K+ channel that is sensitive to two polypeptide toxins (MCD peptide and dendrotoxin I) that produce spectacular effects on brain function. A heterogeneous expression of this K+ channel was observed throughout the brain. High mRNA contents were observed in the granule cells of the gyrus dentatus as well as in pyramidal cells of the Ammon horn (CA3 greater than CA1) and in the cerebellum. Conversely, low levels of expression were found in basal ganglia (caudate putamen, globus pallidus, and ventral pallidum).     

Age-Related Differences and Relationships Between Elements in Human Amygdala and Other Limbic System or Basal Ganglia

To elucidate the compositional changes of the amygdala with aging, the authors investigated age-related differences of elements in human amygdalae. In addition, the relationships between the amygdala and other brain regions were investigated from a viewpoint of elements. After ordinary dissections at Nara Medical University were finished, the amygdalae were removed from the cerebra of the subjects who consisted of 22 men and 23 women, ranging in age from 70 to 101 years. In addition, the hippocampus, dentate gyrus, mammillary body of the limbic system and the caudate nucleus, putamen, and globus pallidus of the basal ganglia were also removed from the identical cerebra. After the brain samples were incinerated with nitric acid and perchloric acid, the element contents were determined by inductively coupled plasma-atomic emission spectrometry. It was found that both the Ca and Mg contents increased significantly in the amygdalae with aging, but the other five element contents (P, S, Zn, Fe, and Na) did not change significantly in the amygdalae with aging. Regarding the relationships among elements, very significant or significant direct correlations were found among the Ca, P, and Mg contents in the amygdalae. To explore the relationships between the amygdala and either other limbic system or basal ganglia, the correlations between seven elements of the amygdala and hippocampus, dentate gyrus, or mammillary body, and between those of the amygdala and caudate nucleus, putamen, or globus pallidus which derived from the identical cerebra, were analyzed with Pearson’s correlation. It was found that regarding the four elements of Ca, P, Mg, and Fe, a close relationship existed between the amygdala and hippocampus, globus pallidus, or mammillary body.