F. Ikuta

Parkinson's disease: the presence of Lewy bodies in Auerbach's and Meissner's plexuses

SummaryWe systematically studied the enteric nervous system of the alimentary tract in seven patients with Parkinsons disease. In all patients, characteristic inclusions histologically and ultrastructurally identical to Lewy bodies were found in Auerbachs and Meissners plexuses. They were most frequent in the Auerbachs plexus of the lower esophagus. Lewy bodies were found in 8 out of 24 age-matched nonparkinsonian patients. However, they were obviously small in number. These findings clearly indicate that the plexuses are also involved in Parkinsons disease.

Mitochondrial angiopathy in cerebral blood vessels of mitochondrial encephalomyopathy

SummaryWe studied cerebral blood vessels of two autopsied patients with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS). All the main cerebral arteries in the proximal portion at the brain base and more distal portion at the cortical surface, as well as within the brain parenchyma were examined by electron microscopy. There was a striking increase in number of mitochondria in the smooth muscle and endothelial cells, which were most prominent in the pial arterioles and small arteries up to 250 μm in diameter and less frequent and severe in the larger pial arteries and intracerebral arterioles and small arteries. These vascular changes have not hitherto been described in MELAS, or in other disorders affecting blood vessels of the brain and other organs. It is suggested that the vascular changes are caused by primary mitochondrial dysfunction in the vascular smooth muscle and endothelial cells of the brain and that they constitute the pathogenic base of the brain lesions and their unusual distribution pattern in MELAS.

Parkinson's disease : an immunohistochemical study of Lewy body-containing neurons in the enteric nervous system

SummaryWe performed immunohistochemical analysis of specimens from three autopsied patients with Parkinsons disease, using antibodies to tyrosine hydroxylase (TH), vasoactive intestinal polypeptide (VIP), somatostatin, met-enkephalin, leu-enkephalin and substance P in an attempt to reveal the types of neurons that contain Lewy bodies (LBs) in the paravertebral and celiac sympathetic ganglia and in the enteric nervous system of the alimentary tract. In the sympathetic ganglia, almost all LB-containing neuronal cell bodies and processes were immunoreactive for TH. In the alimentary tract, however, most LBs were found in the VIP-immunoreactive (VIP-IR) neuronal cell bodies and processes. In spite of the significant presence of TH-IR neuronal cell bodies and processes in the alimentary tract, LB-containing TH-IR neuronal elements were rarely encountered. These findings indicate that in the alimentary tract, the VIP neuron system is mainly involved in the disease process of Parkinsons disease.

Hereditary dentatorubral‐pallidoluysian atrophy Clinical and pathologic variants in a family

We describe a family showing dentatorubral-pallidoluysian atrophy. Three patients appeared through three successive generations and displayed a wide variety of clinical pictures. The male proband with onset in childhood showed progressive myoclonus epilepsy syndrome. The father experienced cerebellar ataxia, myoclonus, and mild dementia starting in middle age; the paternal grandmother had progressive symptoms of cerebellar ataxia, choreiform movements, and dementia, but neither myoclonus nor epilepsy in senescence. Neuropathologic examination of two patients, the proband and the paternal grandmother, revealed combined degeneration of the dentatorubral and pallidoluysian systems and obvious degeneration involving the striatum in the proband and the cerebellar cortex in the grandmother. The present study indicates that this disease can include many clinical and pathologic variants even in the same family.

Creutzfeldt‐Jakob disease in a patient with a cadaveric dural graft

We report a 26-year-old woman with Creutzfeldt-Jakob disease (CJD) who had received cadaveric dural material 33 months before the onset of neurologic symptoms. This is the fourth case in which a dural graft was the putative source of the CJD agent. All four cases had the grafting before changes in the sterilization procedure adopted in 1987 to inactivate the CJD agent.

Distribution of serotonin-containing cell bodies in the brainstem of the human fetus determined with immunohistochemistry using antiserotonin serum

The distribution of serotonin (5HT) neurons was investigated in the brainstem of 8 human fetuses ranging in age from 15 to 27 weeks of gestation. We conducted the peroxidase-antiperoxidase (PAP) immunohistochemical technique using antiserotonin serum to detect the cell bodies of 5HT-containing neurons. Positively stained 5HT neurons were clearly demonstrated in the brainstem of all fetuses examined. They varied in shape, showing round to oval cell bodies with unipolar, bipolar, or multipolar processes. A large number of 5HT neurons were located in the midline raphe nuclei. In addition, numerous 5HT neurons were observed widely in the other tegmental areas. The nuclei containing 5HT neurons were listed according to the terminology by Olszewski and Baxter for human brainstem, and an atlas was given. The distribution of 5HT neurons in the raphe nuclei of human fetuses was essentially similar to those of many mammals already reported. However, the lateral extension of 5HT neurons to the other tegmental areas beyond the midline raphe nuclei was much greater in human fetuses compared to other mammals.

Lewy bodies in the lower sacral parasympathetic neurons of a patient with Parkinson's disease

SummaryLewy bodies were observed incidentally in the neurons of the dorsal group of nucleus intermediolateralis of the 3rd sacral segment of the spinal cord in a 74-year-old male with Parkinsons disease. The findings indicate the degeneration of the preganglionic parasympathetic neurons innervating the internal anal sphincter. The correlation between the findings and the mechanism of constipation in this disease are discussed.

Appearance and distribution of fetal brain macrophages in mice

SummaryA study on the localization of fetal and neonatal brain macrophages of mice from embryonic day 10 (E10) to postnatal day 21 (P21) was carried out immunohistochemically using a monoclonal antibody against a macrophage differentiation antigen (Mac-1) and the labeled avidin-biotin technique. In the central nervous system, the macrophages recognized first were mainly located in the choroid plexuses of the fourth and lateral ventricles at E14. Their number increased at E17–P3 and gradually decreased thereafter. In the cerebral parenchyma, a few macrophages appeared at E14 in the matrix cell layer. They were also detected in the migrating zone at E15, E17 and in the cortical plate at E19. Mapping of positive cells at the stage of neuroblast formation (E15, E17, E19) disclosed the precise distribution of cerebral macrophages. The macrophages that appeared first in the choroid plexuses at E15 may be derived from the subarachnoid vessels, which extend into the stroma of the choroid plexuses when the matrix cell layer invaginates into the lateral ventricle to form the choroid plexuses. Almost all of the macrophages recognized in the cerebral parenchyma disappeared at P9 when the cytoarchitecture seemed to be completed. In the cerebellum, which develops later than the cerebrum, macrophages appeared after birth and were located mainly in the internal granular layer. The brain macrophages always appeared in the regions where cell proliferation and brain remodeling are most active at each stage. These findings suggest that fetal and neonatal brain macrophages may play an important role in scavenging degenerated cells and cell debris during histogenesis of the central nervous system.

Pleiotropic molecular defects in energy-transducing complexes in mitochondrial encephalomyopathy (MELAS)

The extent of molecular defects in the mitochondrial energy-transducing system was examined in autopsied tissues of a 14-year-old male with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) in order to elucidate the underlying molecular and genetic abnormalities. The patient also had other multiorganic disorders: hypertrophic cardiomyopathy, nephrotic syndrome, and pseudohypoparathyroidism. Enzymic activities of complex I and IV were severely decreased, and those of complex III and V were mildly decreased in the mitochondria isolated from various tissues, but the severity of the deficiencies varied from tissue to tissue. In contrast, complex II and citrate synthase activities were normal or were decreased to a lesser extent than the enzymic activities of other complexes in all the tissues examined. These results suggest that the energy-transducing complexes, namely complexes, I, III, IV, and V, that contain mitochondrially synthesized subunits, were selectively affected. Immunoblot analysis demonstrated that the decreased enzymic activities were based on decreased contents of subunits in these complexes. The multiorganic manifestation of the disorder may result from wide and uneven distribution of abnormal mitochondria that have pleiotropic molecular defects in the energy-transducing complexes among the organs of the patient.

Stability of messenger RNA in postmortem human brains and construction of human brain cDNA libraries

We studied stabilities of poly(A)+-RNA in postmortem mouse and human brains for up to 12 hours. The yields of total RNA were not changed significantly during postmortem periods either in mouse brains or human brains. Cell-specific cDNA probes were used to evaluate postmortem stability of poly(A)+-RNA in each cell type in the central nervous system. We used neuronspecific enolase (NSE), S-100β (S-100), and myelin-associated glycoprotein (MAG) for molecular markers of neuron, astrocyte, and oligodendrocyte, respectively. There was no detectable degradation of mRNAs coding for NSE, S-100, and MAG during the postmortem periods on Northern blot hybridization analyses. These results indicate that intact mRNAs expressed in neuron, astrocyte, or oligodendrocyte can be isolated from postmortem brains for up to 12 hours after death. Using poly(A)+-RNA thus isolated from two postmortem human brains, we constructed directional cDNA libraries and demonstrated the presence of full-length cDNAs for NSE, S-100, and MAG on Southern blot hybridization analysis. The present data should encourage studies on altered gene expressions in human brain in various neurologic diseases.