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[Semi-quantitative method of N-isopropyl-(123I)-p-iodoamphetamine accumulation in cerebrum: cerebrum to cerebellum accumulation ratio].

Semi-quantitative method of N-isopropyl-(123I)-p-iodoamphetamine (123I-IMP) accumulation in cerebrum by using 123I-IMP SPECT was tried. Ratio of counts in whole cerebrum to those in normal cerebellum was calculated, and this accumulation is defined as cerebrum to cerebellum accumulation ratio. In group of patients with dementia or patients who were remaining in bed, significantly low accumulation ratio was observed, while in "normal" group, no differences in sex and aging were observed. Calculation of cerebrum to cerebellum accumulation ratio was concluded as a useful method of evaluating the accumulation of 123I-IMP in cerebrum.

Amphetamines↗

Synthesis of arachidonoyl coenzyme A and docosahexaenoyl coenzyme A in synaptic plasma membranes of cerebrum and microsomes of cerebrum, cerebellum, and brain stem of rat brain.

Synthesis of arachidonoyl CoA and docosahexaenoyl CoA in homogenates and microsomes from cerebrum, cerebellum, and brain stem and in synaptic plasma membranes from cerebrum of control rats and rats undergoing bicuculline-induced status epilepticus were studied. Arachidonoyl CoA synthesis was 3-5 times higher than docosahexaenoyl CoA in homogenates and microsomes. The synaptic plasma membranes showed only 1.5- to 2.5-fold higher activity. The presence of Triton X-100 (0.1%) in the incubation medium did not alter the activity of arachidonoyl CoA synthesis but did increase the synthesis of docosahexaenoyl CoA in homogenates, microsomes, and especially in synaptic plasma membranes. The synthesis of these polyenoic fatty acyl CoAs were 4-6 times higher in microsomes than in homogenates. Synaptic plasma membranes exhibited about the same amount of activity as homogenates in the synthesis of docosahexaenoyl CoA, but only half the activity of the latter in arachidonoyl CoA synthesis. The synthesis of arachidonyl CoA and docosahexaenoyl CoA in cerebral homogenates and microsomes was higher than that of cerebellum and brain stem. The apparent Km values for labeled arachidonic acid (17 microM) and docosahexaenoic acid (12 microM) in synaptic plasma membranes were lower than the values for microsomes isolated from different brain regions. The Vmax values were also 4-10 times lower. Microsomes from different regions did not differ in their apparent Km values, but did show variations in apparent Vmax values. Cerebellar microsomes showed lower Vmax values than the other two regions. The presence of Triton X-100 caused a significant decrease in the apparent Km values with little change in the Vmax values. Bicuculline-induced seizures did not alter the kinetic properties of arachidonoyl CoA and docosahexaenoyl CoA synthesis, except there was a significant decrease in the apparent Km and Vmax values for cerebellar microsomal docosahexaenoyl CoA synthesis. In conclusion, there were marked differences in the activation of polyenoic fatty acids in different parts of the brain and in subcellular fractions. Although bicuculline-induced convulsions accumulate free polyenoic fatty acids in the brain, no changes were detected when the fatty activation was assayed with exogenous cofactors, except in cerebellum.

Acyl Coenzyme A↗

Interactions between bacterial pyrogen and proteolipid extracted from the cerebrum. (III). Variation in affinity of proteolipid proteins derived from rabbit, rat and chicken cerebrums to bacterial pyrogen.

We undertook comparative studies on the binding of cerebral proteolipids to LPS using rabbits, rats and chickens in order to clarify the differences in inactivating effects of proteolipids from these three sources on the pyrogenicity of LPS. The Sephadex LH-20 column elution profiles of lipid phosphorus and cerebrosides were not significantly different for the three sources of proteolipid, but a larger amount of proteolipid-protein possessing LPS pyrogenicity inactivating potency was eluted with chloroform (C)/methanol(M) (4:1) in rats and chickens than in rabbits. A complex of proteolipid-protein with LPS was obtained in C effluent from incubation mixtures of rat and chicken proteolipids with LPS, corresponding to our previous observation with rabbit proteolipid. The increasing order of binding capacity of the proteolipids derived from the three species was as follows: chicken, rat and rabbit, which was in parallel with pyrogenic inactivating potency. From these data, we suggest that the difference in pyrogenic inactivating potency among the proteolipids of some species depends on the difference in binding capacity of the proteolipids to LPS or probably lipid A.

Animals↗

Dose- and duration-dependent alterations by tellurium on lipid levels: differential effects in cerebrum, cerebellum, and brain stem of mice.

The effect of various doses of sodium tellurite (1/50 LD50=0.4 mg/kg, 1/25 LD50=0.8 mg/kg, and 1/10 LD50=2.0 mg/kg body weight orally) on the lipid levels (cholesterol, triglycerides, phospholipids, esterified fatty acids, gangliosides, and total lipids) in the cerebrum, cerebellum, and brainstem of male albino mice was studied after 7 and 15 d of treatment. Sodium tellurite (2.0 mg/kg body weight) for 7 d has an apparent effect on the depletion of cholesterol, triglycerides, phospholipids, esterified fatty acids, and total lipids. The cholesterol content was decreased significantly in the cerebrum, cerebellum, and brainstem after 7 d of treatment with a 2.0-mg/kg dose compared to the control. On the other hand, treatment for 15 d with doses of 0.4, 0.8, and 2.0 mg/kg body weight resulted in a significant and dose-dependent increment in cholesterol level in the cerebrum, cerebellum, and brainstem. The triglycerides content was decreased significantly in the cerebrum, cerebellum, and brainstem with the 2.0-mg/kg dose after 7 d of treatment. The doses of 0.4, 0.8, and 2.0 mg/kg orally for 15 d resulted in a significant and dose-dependent depletion of triglycerides in the cerebrum, cerebellum, and brainstem. All the doses of tellurium (0.4, 0.8, and 2.0 mg/kg) both for 7 and 15 d have depleted the level of phospholipids in varying degrees of significance in the cerebrum, cerebellum, and brainstem. However, the level of esterified fatty acids was decreased significantly with the 2.0-mg/kg dose of tellurium for 7 d but increased with the 0.4-mg/kg dose for 15 d in the cerebrum and cerebellum. The level of gangliosides was depleted in the cerebrum but elevated in the cerebellum and brainstem after receiving a 2.0-mg/kg dose of sodium tellurite for 7 d. The content of gangliosides was increased with doses of 0.4 and 0.8 mg/kg but decreased with 2.0 mg/kg for 15 d in the cerebrum, cerebellum, and brainstem. The total lipids content was depleted significantly and dose dependently after 7 and 15 d of treatment in the cerebrum, cerebellum, and brainstem. These results suggest that sodium tellurite affects the lipids content differentially in various parts of the mice brain.

Animals↗

Automated cerebrum segmentation from three-dimensional sagittal brain MR images.

We present a fully automated cerebrum segmentation algorithm for full three-dimensional sagittal brain MR images. First, cerebrum segmentation from a midsagittal brain MR image is performed utilizing landmarks, anatomical information, and a connectivity-based threshold segmentation algorithm as previously reported. Recognizing that cerebrum in laterally adjacent slices tends to have similar size and shape, we use the cerebrum segmentation result from the midsagittal brain MR image as a mask to guide cerebrum segmentation in adjacent lateral slices in an iterative fashion. This masking operation yields a masked image (preliminary cerebrum segmentation) for the next lateral slice, which may truncate brain region(s). Truncated regions are restored by first finding end points of their boundaries, by comparing the mask image and masked image boundaries, and then applying a connectivity-based algorithm. The resulting final extracted cerebrum image for this slice is then used as a mask for the next lateral slice. The algorithm yielded satisfactory fully automated cerebrum segmentations in three-dimensional sagittal brain MR images, and had performance superior to conventional edge detection algorithms for segmentation of cerebrum from 3D sagittal brain MR images.

Algorithms↗

Disruption of the blood-brain barrier in cerebrum and brain stem during acute hypertension.

The purpose of this study was to examine hemodynamic mechanisms of protection of the blood-brain barrier in the brain stem during acute hypertension. We used a new method to examine the microcirculation of the brain stem. Intravital fluorescent microscopy and fluorescein-labeled dextran were used to evaluate disruption of the blood-brain barrier during acute hypertension in rats. During control conditions, pressure (servo null) in arterioles (60 microns in diameter) was 50 +/- 2% (mean +/- SE) of systemic arterial pressure in the cerebrum and 67 +/- 1% of systemic arterial pressure in the brain stem (P less than 0.05 vs. cerebrum). In the cerebrum, pial venous pressure increased from 7 +/- 1 to 25 +/- 2 mmHg during acute hypertension, and there was marked disruption of the blood-brain barrier in venules (26 +/- 2 leaky sites). In contrast, in the brain stem, pial venous pressure increased from 4 +/- 1 to only 8 +/- 1 mmHg (P less than 0.05 vs. cerebrum), and there was minimal disruption of the blood-brain barrier in venules (1.5 +/- 0.6 leaky sites, P less than 0.05 vs. cerebrum). During acute hypertension, increases in blood flow (microspheres) were less in brain stem than in cerebrum. The findings suggest distribution of vascular resistance differs in the brain stem and cerebrum under control conditions, whereas large arteries account for a greater fraction of resistance in cerebrum; pial venous pressure increases less in brain stem than cerebrum during acute hypertension, so that the blood-brain barrier is protected.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗

The cholinergic receptor-linked phosphoinositide metabolism in mouse cerebrum and cerebellum in vivo.

The cholinergic receptor-linked poly-phosphoinositide hydrolysis was studied in mouse cerebrum and cerebellum after prelabeling the brain with [3H]inositol. I.p. injection of Li (8 meq/kg) to C57Bl/6J mice for 4 h resulted in 14- and five-fold increases in [3H]inositol-labeled inositol monophosphate (IP1) in cerebrum and cerebellum, respectively. The labeled inositol bisphosphate (IP2) was also increased 83 and 19% in cerebrum and cerebellum, respectively. Prior injection of atropine (100 mg/kg) resulted in inhibition of Li-induced increases in labeled IP1 by 74 and 56% in cerebrum and cerebellum, respectively. Administration of pilocarpine (20 mg/kg) to the Li-treated mice for 30 min resulted in further increases in labeled IP1 and IP2 and a concomitant decrease in labeled inositol in cerebrum but not in cerebellum. Mass measurements of IP1 and IP2 isomers by HPLC revealed that inositol 1-monophosphate (Ins(1)P), inositol 4-monophosphate (Ins(4)P) and inositol 1,4-bisphosphate (Ins(1,4)P2) were all increased by pilocarpine administration in the Li-treated mouse cerebrum. The effects of pilocarpine administration in mouse cerebrum (increases in IP1 and IP2) could be completely inhibited by preinjection of atropine. Atropine injection also decreased the levels of inositol 1,4,5-trisphosphate [Ins(1,4,5)P3]. Surprisingly, a decrease in Ins(1,4,5)P3 level was also found in non-Li-treated mice after pilocarpine administration (30 mg/kg, 10-40 min). Except for the increase (20%) in [32P]-labeled PIP in the cerebrum, Li or Li together with pilocarpine administration did not alter the levels of [3H]inositol or [32P]phosphate-labeled phosphoinositides.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Stimulatory effects of growth hormone and thyroxine on the concentration of gangliosides in the Snell dwarf cerebrum.

The concentration of gangliosides in the Snell dwarf mouse cerebrum was monitored from postnatal day 5 to day 40. In the dwarf cerebrum, the concentration of total gangliosides increased up to postnatal day 20 and then stopped, whereas in the control cerebrum, it continued to increase up to postnatal day 40. At postnatal day 40, the ganglioside level in the dwarf cerebrum was 70% of that in the control cerebrum. Among the ganglioside species, the concentrations of GM4, GM2, GM1, GD1a, GD3, GD1b, GT1b, and GQ1b were significantly lower in the dwarf cerebrum than in the controls at postnatal day 40. The reduced concentrations of ganglioside species GM2, GD1a, GD3, GD1b, and GQ1b were completely restored by administration of bovine growth hormone (GH) during the first 20 days of postnatal life. The reduced concentration of the GM1 and GM4 species were most efficiently restored by administration of bovine GH plus thyroxine (T4) during the second 20 days of postnatal life. These results indicate that the lower ganglioside concentrations in the dwarf cerebrum can be elevated by hormone therapy and that there exist distinct GH and T4 actions on the enzymes participating in ganglioside metabolism.

Animals↗

Mechanics and composition of arterioles in brain stem and cerebrum.

The goal of this study was to compare mechanics and composition of arterioles in brain stem and cerebrum. We calculated stress and strain of pial arterioles in anesthetized rats from measurements of pial arteriolar pressure (servo-null), diameter, and cross-sectional area of the vessel wall. Composition of pial arterioles was quantitated using point-counting stereology. Before deactivation of smooth muscle with ethylenediaminetetraacetic acid (EDTA), pial arteriolar pressure and diameter were 28 and 30% greater (P less than 0.05) in brain stem than cerebrum. After EDTA, diameter of arterioles was similar in brain stem and cerebrum. Cross-sectional area of the arteriolar wall was 32% greater (P less than 0.05) in brain stem than cerebrum. Stress-strain curves indicated that distensibility of pial arterioles is greater in brain stem than cerebrum. The proportion of nondistensible (collagen and basement membrane) to distensible (elastin, smooth muscle, and endothelium) components was 20% less (P less than 0.05) in brain stem than cerebral arterioles. We conclude that 1) cross-sectional area of the vessel wall in arterioles of comparable size is greater in brain stem than cerebrum, 2) distensibility of arterioles is greater in brain stem than cerebrum, despite greater cross-sectional area of the arteriolar wall in brain stem, and 3) the proportion of elastic components is greater in brain stem than cerebral arterioles, which may contribute to greater arteriolar distensibility in brain stem.

Animals↗

Tellurium-induced dose-dependent impairment of antioxidant status: differential effects in cerebrum, cerebellum, and brainstem of mice.

The effect of various doses of sodium tellurite (0.4, 0.8, and 2.0 mg/kg body weight, orally) on the activity of antioxidant enzymes (glutathione peroxidase, glutathione reductase, glutathione-S-transferase, and catalase) and content of glutathione and thiobarbituric acid reactive substances (TBARSs) in the cerebrum, cerebellum, and brainstem of male albino mice was studied after 15 d of treatment. All of the doses of tellurium (0.4, 0.8, and 2.0 mg/kg body weight, orally) have depleted the activity of antioxidant enzymes and the content of glutathione dose dependently in the cerebrum, cerebellum, and brainstem and it was significant with the dose of 2.0 mg/kg. On the other hand, the 2.0-mg/kg dose of tellurium has significantly elevated the content of TBARSs in the cerebrum and cerebellum. The 0.8-mg/kg dose of tellurium has significantly depleted the activities of glutathione peroxidase in the cerebrum and brainstem, glutathione-Stransferase in the cerebrum and cerebellum, catalase in the brainstem, and the content of glutathione in the cerebrum and cerebellum. In contrast, this dose has significantly elevated the content of TBARSs in the cerebrum and cerebellum. However, the depletion in the activity of glutathione reductase with various doses of sodium tellurite was not significant in any brain part of mice. The result suggests that sodium tellurite differentially affects the antioxidant status within various parts of the mice brain.

Animals↗

Segmentation and three-dimension reconstruction of Chinese digitized human cerebrum.

OBJECTIVE: A 3D digitized visible model of human cerebrum was built to provide anatomical structure for making plans of cerebral surgical operation and realizing accurate simulation of cerebrum on computer. METHODS: Transverse sectional anatomy data of the cerebrum were chosen from the first Chinese visible human (one male and one female). Semi-automated segmentation and Photoshop software were selected to segment cerebral cortex, white matter, basal nuclei, lateral ventricle, hippocampus, etc. On personal computer, the segmented structures were reconstructed in 3D with volume rendering reconstruction and surface rendering reconstruction. RESULTS: Two accurately segmented images of the main structures of cerebrum were completed. The reconstructed structures can be displayed singly, in small groups or as a whole and can be continuously rotated in 3D space at different velocities. CONCLUSION: Combining volume-rendering reconstruction with surface rendering reconstruction overcomes the defects of surface rendering reconstruction that lack of internal anatomical information, which provides a new method for 3D reconstruction. The reconstructed cerebrum and the main internal structures are realistic, which demonstrates the natural shape and exact position of the structures. It provides an accurate model for the automated segmentation algorithmic study and provides a digitized anatomical mode of cerebrum.

China↗

Segmental vascular responses to acute hypertension in cerebrum and brain stem.

The goal of this study was to examine hemodynamic mechanisms that contribute to regional differences in autoregulation during acute hypertension. We measured blood flow (microspheres) and pressure in pial arteries (approximately 160 microns) of anesthetized cats and calculated resistance of large and small vessels in cerebrum and brain stem. Moderate elevation of aortic pressure increased resistance of both large and small vessels in cerebrum but only small vessels in brain stem. During severe hypertension, resistance of both large and small vessels in cerebrum decreased and blood flow increased markedly. In contrast, in the brain stem large artery resistance did not change, small vessel resistance increased, and blood flow increased only modestly during severe hypertension. Pial artery pressure was 20 mmHg higher in brain stem than cerebrum during control conditions and 30-50 mmHg higher during moderate and severe hypertension. We conclude that resistance of large arteries is less and thus pial artery pressure is higher in brain stem than cerebrum under control conditions. More effective autoregulation in the brain stem than cerebrum during severe hypertension is due to greater resistance of small, not large, cerebral vessels.

Animals↗

Body weight deficit in the absence of reduction in cerebrum weight and nucleic acid content in progeny of swine restricted in protein intake during pregnancy.

Fifty-six castrated male progeny of crossbred (Chester White x Landrace x Large White x Yorkshire) dams fed an adequate diet (control, C), a control diet fed at one-third of C (restricted, R), or diets severely deficient in protein (PF) or restricted in nonprotein calories (RCal) were killed at age 25 weeks. Dams were fed their respective diets in the following regimens: C, 1.8 kg (6000 kcal daily) throughout pregnancy; R, 0.6 kg of C diet daily for 70 days, then 1.8 kg of C daily to parturition at about 114 days; PF, 1.8 kg of a "protein-free" diet (less than 0.2% protein) throughout pregnancy; RCal, 0.6 kg daily (2000 kcal) of a diet containing three times the concentration of protein, minerals, and vitamins provided by the C diet for 70 days, then 1.8 kg of C daily to parturition. All dams were fed an adequate diet ad libitum through a 28-day lactation. Castrated male progeny were assigned to one of two replicates based on birth date and fed a corn-soybean meal diet ad libitum from weaning to age 25 weeks, supplemented from age 10 to 12 weeks with 0, 110, or 220 mg/kg of thyroprotein (iodinated casein). Cerebrum weight was unaffected by maternal diet, despite a significant (P less than 0.001) reduction in body weight of progeny of PF dams compared with other groups, resulting in a higher relative cerebrum weight in progeny of PF dams than in progeny of C, R, and RCal dams. Absolute and relative weights of RNA, DNA, and total protein in cerebrum were unaffected by maternal diet. Thyroprotein supplementation to the diet of the progeny had no effect on cerebrum weight or its protein or nucleic acid content. It is concluded that maternal protein deprivation but not restriction of feed or nonprotein calorie intake to one-third of recommended allowance during gestation results in stunting of body weight in young adult progeny but does not affect cerebrum weight, cerebrum cell number (DNA), or protein synthetic activity (RNA), or RNA-to-protein ratio.

Animals↗

Differential sequestration of parasitized erythrocytes in the cerebrum and cerebellum in human cerebral malaria.

Sequestration of parasitized red blood cells (PRBC) in the microvessels results in impairment of microcirculation with organ dysfunction in complicated human Plasmodium falciparum malaria. In cerebral malaria patients, the percentage of small blood vessels with PRBC sequestration is higher in the brain than in other organs. The clinical severity of cerebral malaria depends on the level of PRBC sequestration in the brain. In our study, postmortem samples from cerebrum and cerebellum of 16 patients who died of P. falciparum malaria were examined and compared using light microscopy. In the cerebellum, the percentage of microvessels with PRBC sequestration was higher than that in the cerebrum. The difference in sequestration rates between cerebrum and cerebellum is statistically significant (P < 0.05). There is a higher degree of vascularity in the cerebellum (7 vessels/mm2) than in the cerebrum (5 vessels/mm2), and the difference is also statistically significant (P < 0.025). Perivascular hemorrhages also occur more frequently in the cerebellum than in the cerebrum. The results of this study, which show that differential sequestration of PRBC occurs in the microvessels of the cerebrum and cerebellum, explain the varied neurologic manifestations that result from cerebral and cerebellar dysfunction in human cerebral malaria. This study also reveals the necessity of postmortem histologic examination of the cerebellum in every suspected case of cerebral malaria.

Brain↗

[Influences of excess iodine on thyroid hormone concentrations in cerebrum of filial mice and intervention of selenium].

OBJECTIVE: To study the influence of excessive iodine intake on thyroid hormones in cerebrum of filial mice and intervention of selenium. METHODS: 60 Balb/c mice were divided randomly into 4 groups: control group, iodine group, selenium group and iodine plus selenium group and given tap water, tap water containing iodine 3000 microg/L, tap water containing selenium 200 microg/L and tap water containing iodine plus selenium 200 microg/L respectively as drinking water. At the end of the fourth month, the mice mated. Thyroid hormones and TSH in serum and in cerebrum of filial mice were determined at the postnatal 0, 14th and 28th day. RESULTS: At the postnatal 14th day, serum TT4 level was lower significantly, and serum TSH was higher in iodine group than those in control group and in the iodine plus selenium group. At the postnatal 0 day and 14th day, thyroid hormone concentrations in the cerebrum of progeny of mice were lower significantly in iodine group than those in control group, selenium group and iodine plus selenium (P < 0.05). No significant difference was observed among the four groups in TT4, TT3 and rT3 concentrations in serum and cerebrum at the postnatal 28th day. CONCLUSION: Excessive iodine intake can change thyroid hormone concentrations in the cerebrum of progeny of mice and selenium supplementation exerted favorable effects on it.

Animals↗

Developmentally regulated expression of a brain specific species of chondroitin sulfate proteoglycan, neurocan, identified with a monoclonal antibody IG2 in the rat cerebrum.

The mammalian brain contains many species of proteoglycan. To identify each proteoglycan species, we have raised monoclonal antibodies against soluble chondroitin sulfate proteoglycans purified from 10-day-old rat brains. One monoclonal antibody, named monoclonal antibody 1G2, recognized two proteoglycan species with 220,000 and 150,000 mol. wt core glycoproteins (chondroitin sulfate proteoglycan-220 and chondroitin sulfate proteoglycan-150). Partial amino acid sequences of N-termini of their core proteins coincided with those of neurocan, a brain-unique chondroitin sulfate proteoglycan species, whose complete coding sequence was recently reported [Rauch et al. (1992) J. biol. Chem. 269, 19,536-19,547]. Western blots revealed that chondroitin sulfate proteoglycan-220 became detectable in the rat cerebrum on embryonic day 14, and that it disappeared from the brain around postnatal day 30. In contrast, a fairly large amount of chondroitin sulfate proteoglycan-150 remained in the mature brain. Immunohistochemical studies revealed that 1G2 antigen was first localized in the preplate zone, then both in the marginal zone and in the subplate of the rat cerebrum on embryonic day 16, prior to arrival of the first thalamic afferents at the cortex. On embryonic day 20, immunolabeling with monoclonal antibody 1G2 began to spread from the subplate into the developing cortical plate. On postnatal day 10, the neuropil of the cerebrum, except for the barrel field, was diffusely stained with the antibody, intensely in the hippocampus and superficial layers (I-III) of the cerebral cortex and weakly elsewhere. The barrel hollows were stained very weakly compared with the barrel walls at this stage. The immunoreactivity in the hippocampus and superficial cortical layers was weakened in the mature brain, so that no particular staining pattern, but weak and diffuse staining was observed in the adult rat cerebrum. The 1G2 antigen was immunohistochemically associated largely with glial fibrillary acidic protein-positive cells in primary cultures of the neonatal rat cerebrum. Both chondroitin sulfate proteoglycan-220 and chondroitin sulfate proteoglycan-150 were detected in the conditioned media not only of highly enriched cultures of fetal rat cortical neurons but also of pure cultures of mature astrocytes; more (12- to 20-fold) in the astrocyte conditioned media. Astrocytes, in addition to neurons, may be a cellular source of neurocan in brain at least under certain physiological conditions. The spaciotemporal expression pattern of 1G2 epitope-bearing proteoglycan, or neurocan, suggests that this proteoglycan species plays some roles at least in forming the elongation pathway for early cortical afferent fibers as well as the functional barrel structure in the somatosensory cortex.

Amino Acid Sequence↗

The expanded CAG repeat associated with juvenile Huntington disease shows a common origin of most or all neurons and glia in human cerebrum.

We have analyzed the size of the expanded poly(CAG) associated with juvenile Huntington disease in the cerebra and the cerebella of five patients. The expanded poly(CAG) was always longer in the cerebrum than in the cerebellum, but the difference in size varied from patient to patient. Except for one patient who possessed an unusually large expansion, very little heterogeneity of size was detected within the cerebrum or within the cerebellum. The larger size of the expanded poly(CAG) in cerebrum must therefore have resulted from a single expansion event that took place early in cerebral development. In both cerebrum and cerebellum, the size of the expanded allele of gray matter was identical to that of white matter. We conclude that most if not all neurons and glia of cerebrum are descended from a common bipotent precursor, which segregated early in neurogenesis from the lineage leading to cerebellar neurons and glia.

Adolescent↗