Age-Related Changes of Elements in the Coronary Arteries of Monkeys in Comparison with Those of Humans

To elucidate compositional changes of the coronary artery with aging, the authors investigated age-related changes of elements in the coronary arteries of rhesus and Japanese monkeys by direct chemical analysis in comparison with the coronary arteries of Japanese and Thai. Used monkeys consisted of 38 rhesus monkeys and 23 Japanese monkeys, ranging in age from newborn to 33 years. After perfusion with a fixative, the hearts were resected from the monkeys, and the anterior interventricular branches of the left coronary artery and the right coronary arteries were resected from the hearts. After ashing of the arteries, element contents were determined by inductively coupled plasma-atomic emission spectrometry. It was found that the Ca and P contents did not increase in both the left and right coronary arteries of rhesus and Japanese monkeys at old age. The average contents of Ca and P decreased by 13% and 25% in the left coronary arteries more than 20 years of age in comparison with those below 20 years of age, whereas they decreased by 4% and 15% in the right coronary arteries more than 20 years of age in comparison with those below 20 years of age. This finding indicated that atherosclerosis scarcely occurred in both the left and right coronary arteries of rhesus and Japanese monkeys at old age. In contrast with monkeys, atherosclerosis occurred frequently in the coronary arteries of Japanese and Thai at old age.     

Age-Related Changes of Elements in Human Olfactory Bulbs and Tracts and Relationships Among Their Contents

To elucidate compositional changes of the olfactory bulb and tract with aging, the authors investigated age-related changes of elements in the olfactory bulbs and tracts of Japanese and the relationships among the elements. After ordinary dissection at Nara Medical University was finished, the olfactory bulbs were resected with the olfactory tracts from 40 subjects. The subjects consisted of 15 men and 25 women, ranging in age from 65 to 102 years (average age = 84.6 +/- 7.5 years). After ashing with nitric acid and perchloric acid, element contents in the olfactory bulbs and tracts were analyzed by inductively coupled plasma-atomic emission spectrometry. Seven elements of Ca, P, S, Mg, Zn, Fe, and Na did not change significantly in the olfactory bulbs and tracts with aging. The Ca, P, and S contents of major elements were less than 10 mg/g in all of the olfactory bulbs and tracts. Regarding the relationships among the elements, extremely or very significant direct correlations were found among the contents of Ca, P, Mg, Zn, and Na in the olfactory bulbs and tracts, with one exception. In addition, an extremely significant direct correlation was found between S and Mg contents and a very significant direct correlation was found between P and S contents. As P increased in the olfactory bulb and tract, Ca, Mg, Zn, Na, and S also increased in the olfactory bulb and tract.     

Age-related Changes of Elements in Human Corpus Callosum and Relationships Among These Elements

To elucidate compositional changes of the corpus callosum with aging, the authors investigated age-related changes of elements and relationships with their element contents in the corpus callosum. After ordinary dissection by medical students at Nara Medical University was finished, the genu, trunk, and splenium of the corpus callosum were resected from the subjects ranging in age from 58 to 94 years. The element contents of the corpus callosum were determined by inductively coupled plasma-atomic emission spectrometry. The contents of Ca, P, S, Mg, Zn, Fe, and Na did not change significantly in the genu, trunk, and splenium of the corpus callosum with aging. Regarding the relationships among the element contents, significant correlations were found among the contents of Ca, P, S, Mg, and Fe in all of the genu, trunk, and splenium of the corpus callosum with some exceptions.     

Design, synthesis, and biophysical properties of a helical Abeta1-42 analog: Inhibition of fibrillogenesis and cytotoxicity

The aggregation of amyloid β-peptide (Aβ) into β-sheet-rich aggregates is a crucial step in the etiology of Alzheimer’s disease. Helical forms of Aβ have been suggested to be intermediates in the aggregation process of the peptide in aqueous phase, micelles and membranes. A stable helical Aβ analog would be useful to investigate the role of helical intermediates in fibrillization by Aβ. Here we designed a helical analog by simply cross-linking the Cys residues of A30C, G37C-Aβ1-42 with 1,6-bismaleimidohexane. The analog assumed a weak α-helical conformation in model membranes mimicking lipid raft microdomains of neuronal membranes under conditions in which the wild-type Aβ1-42 formed a β-sheet, indicating the cross-linking locally induced a helical conformation. Furthermore, addition of equimolar helical Aβ analog significantly reduced the amyloid formation and cytotoxicity by Aβ1-42. Thus, our helical Aβ1-42 is not only a model peptide to investigate the role of helical intermediates in fibrillization by Aβ, but also an inhibitor of Aβ-induced cytotoxicity.     

A brain-specific decrease of the tyrosine hydroxylase protein in sepiapterin reductase-null mice--as a mouse model for Parkinson's disease

Sepiapterin reductase (SPR) is an enzyme that acts in the third and final step of tetrahydrobiopterin (BH4) biosynthesis. The human Spr gene locates within the region of 2.5 MB mapped to PARK3, an autosomal dominant form of familial Parkinson’s diseases. In order to explore the role of SPR in the metabolism of BH4, we produced and analyzed Spr-deficient mice. Most of Spr-null mice survived beyond two weeks. Whereas the BH4 contents in the homozygous mutant mice were greatly decreased than those in wild-type and heterozygous mice, the substantial amounts of BH4 were remained even 17 days after delivery. Spr-null mice exhibited severe monoamine deficiencies and a tremor-like phenotype after weaning. The amount of TH protein in the brain of Spr-null mice was less than 10% of wild-type, while TH protein in the adrenal, phenylalanine hydroxylase protein in the liver, and nNOS in the brain were not altered. These data suggest an essential role of SPR in the biosynthesis of BH4, and that the SPR gene could be a candidate gene for PARK3.     

Age-related changes of bone mineral density in human calcaneus, talus, and scaphoid bone

To examine whether the bone mineral density (BMD) decreases uniformly with aging in any spongy bones, the authors investigated age-related changes of BMD in the calcaneus, talus, and scaphoid bone. After the ordinary dissection by medical students was finished, calcanei, tali, and scaphoid bones were resected from the subjects, and BMDs were measured by dual-energy X-ray absorptiometry. Their BMDs seemed to decrease gradually with aging in the calcanei, tali, and scaphoid bones. It was found that there were statistically significant relationships between age and BMD in the men’s and women’s scaphoid bones, women’s tali, and women’s calcanei, but not in the men’s tali and calcanei. It should be noted that there were significant relationships between age and BMD in both men’s and women’s scaphoid bones. In regard to relationship in BMD between the bones of the upper and lower limbs in individuals, it was found that the relationship between the calcaneus and talus was higher than that between the calcaneus and scaphoid bone. This suggests that there is a higher relationship in BMD between the two tarsal bones compared with that between the tarsal and carpal bones.     

Relationships among element contents in the intimal, middle, and external tunicae of the thoracic aorta

To examine an accumulation of elements within the arteries with aging, the authors investigated the element contents in the intimal, middle, and external tunicae of the thoracic aorta. The subjects consisted of six men and four women, ranging in age from 57 to 99 yr. The wall of the thoracic aorta was separated into the intimal, middle, and external tunicae by scrubbing the wall of the thoracic aorta with an edge of slide glass and the element contents were determined by inductively coupled plasma-atomic emission spectrometry. It was found that there were significant relationships among calcium, phosphorus, magnesium, sulfur, and sodium in both the intimal and middle tunicae of the aorta, but not in the external tunica. These results revealed that no significant differences were found in element compositions of deposits between the intimal and middle tunicae.     

Accumulation of calcium and phosphorus accompanied by increase of magnesium and decrease of sulfur in human arteries

To elucidate the accumulation of elements in the arteries with aging, the authors investigated age-related changes of elements in human arteries, such as the thoracic aorta, femoral, basilar, coronary, radial, and common iliac arteries by inductively coupled plasma-atomic emission spectrometry. The subjects consisted of 17 men and 9 women, ranging in age from 55 to 92 yr in the cases of the five arteries, except for the common iliac arteries, in which the subjects consisted of 16 men and 8 women, ranging in age from 65 to 93 yr. It was found that there were significantly direct correlations between calcium and phosphorus contents and between calcium and magnesium contents in all of the six arteries: thoracic aorta, femoral, basilar, coronary, radial, and common iliac arteries. Significantly direct correlations were also found between phosphorus and magnesium contents in the five arteries, except for the basilar artery. In contrast, significantly inverse correlations were found between calcium and sulfur contents and between phosphorus and sulfur contents in the four arteries, except for the coronary and radial arteries. These revealed that the accumulation of calcium and phosphorus in the arteries was accompanied by an increase of magnesium in the arteries and by a decrease of sulfur in the arteries.     

Simultaneous accumulation of calcium, phosphorus, and magnesium in various human arteries

To elucidate compositional changes of the arteries with aging, the authors investigated the relationships among average contents of calcium, phosphorus, sulfur, and magnesium in the arteries by inductively coupled plasma-atomic emission spectrometry. The arteries used were the thoracic and abdominal aortas, coronary, common carotid, anterior, middle and posterior cerebral, vertebral, basilar, internal thoracic, axillary, radial, truncus celiacus, common, internal and external iliac, femoral, popliteal, and umbilical arteries. It was found that high correlations were found between the average contents of calcium and phosphorus, between the average contents of calcium and magnesium, and between the average contents of phosphorus and magnesium in the arteries, but not between the average contents of sulfur and the other elements. These correlations revealed that as the content of calcium and phosphorus increased in the arteries, the magnesium content increased simultaneously in the arteries, but the sulfur content did not. It is likely that magnesium forms compounds with phosphorus in the arteries.     

Age-Related Changes of Elements in the Anterior Commissures and the Relationships Among their Elements

To elucidate compositional changes of the anterior commissure with aging, the authors investigated age-related changes of elements in the anterior commissures and the relationships among their elements. After ordinary dissection at Nara Medical University was finished, the anterior commissures were resected from 45 subjects, ranging in age from 70 to 101 years. The subjects consisted of 22 men and 23 women. After ashing with nitric acid and perchloric acid, the element content of the anterior commissures was determined by inductively coupled plasma-atomic emission spectrometry. The seven element contents of Ca, P, S, Mg, Zn, Fe, and Na did not change significantly in the anterior commissures with aging. Regarding the relationships among their element contents, significant correlations were found among the contents of Ca, Mg, Zn, and Na in the anterior commissures. The gender difference that the Zn content was significantly higher in men than in women was found in the anterior commissure.