Severe neurofibrillary changes were identified in the paraventricular and supraoptic nuclei of elderly individuals using markers for Alzheimer’s disease-related intraneuronal pathology. This neurofibrillary pathology is remarkable in that the magnocellular paraventricular and supraoptic nuclei are particularly resistant to Alzheimer’s disease. Moreover, the changes were observed even in non-demented controls, indicating that they develop independently of Alzheimer’s disease. The alterations in the paraventricular and supraoptic nuclei were consistently accompanied by neurofibrillary changes in the mediobasal hypothalamus.

Summary

The development of the lesion caused by NDDC in the CNS of adult rabbits was studied by killing rabbits receiving NDDC at 6 week intervals. The first changes were seen at 6 weeks in the accessory cuneate nucleus and in Clarke's column. 12 weeks later degenerative changes were seen in the spinocerebellar tracts in the cerebellum, medulla. The rabbits killed after 24 weeks showed severe nerve fibre degeneration in the peripheral white matter of the spinal cord. Changes in peripheral nerves were minimal. This “neuraxonal degeneration” is discussed in relation to similar changes seen in human and animal neuropathology.

The incorporation of neurites into amyloid deposits is an important step in the formation of senile plaques in Alzheimer's disease. It is unknown whether all neuronal types contribute neurites equally to plaques, or whether the processes of certain types are preferentially incorporated. We addressed this question by comparing the incorporation into neocortical plaques of neurites containing the widely distributed neuronal markers chromogranin A (CgA), parvalbumin (PV) and calbindin D-28K (CaBP) in relation to the number of neuronal perikarya expressing each of these substances in the neocortex. We found a consistent, statistically significant ranking, so that CgA-immunoreactive (ir) neurites were preferentially incorporated into plaques in comparison with PV-ir, and PV-ir were favoured over CaBP-ir neurites.

Neurofibromatosis type 1 (NF1) is a common genetic disease that predisposes 30–50 % of affected individuals to develop plexiform neurofibromas. We found that macrophage infiltration of both mouse and human neurofibromas correlates with disease progression. Macrophages accounted for almost half of neurofibroma cells, leading us to hypothesize that nerve macrophages are inflammatory effectors in neurofibroma development and/or growth. We tested the effects of PLX3397, a dual kit/fms kinase inhibitor that blocks macrophage infiltration, in the Dhh-Cre; Nf1^flox/flox mouse model of GEM grade I neurofibroma. In mice aged 1–4 months, prior to development of nerve pathology and neurofibroma formation, PLX3397 did not impair tumor initiation and increased tumor volume compared to controls. However, in mice aged 7–9 months, after tumor establishment, a subset of mice demonstrating the largest reductions in macrophages after PLX3397 exhibited cell death and tumor volume regression. Macrophages are likely to provide an initial line of defense against developing tumors. Once tumors are established, they become tumor permissive. Macrophage depletion may result in impaired tumor maintenance and represent a therapeutic strategy for neurofibroma therapy.

Observations have been made on the structure of the paranodal region at nodes of Ranvier in the sural nerve of patients with diabetic sensory polyneuropathy. The structure of the paranodes was examined with particular attention to the definition and assessment of axoglial dysjunction, which has been claimed to be a characteristic feature of both human and experimental diabetic neuropathy and which has been related to paranodal swelling. In the present series of cases it was not possible to confirm that axoglial dysjunction is a distinctive feature of diabetic polyneuropathy in fibres not undergoing active demyelination or wallerian-type degeneration, neither was excessive paranodal enlargement found.

Summary

Electron microscopic observations are reported on a case of progressive multifocal leukoencephalopathy unassociated with any lympho-proliferative disease. The morphological evidence suggests that the condition may be caused by the replication, in the glial cell nuclei of the central nervous system, of an infective agent belonging, or related, to the papova group of viruses. The possible implications of these observations are briefly discussed.

Summary

The anatomic location and histological appearance of spinal cord epidermoid cysts in a variety of inbred mouse strains was examined. A variable incidence of cysts was found in mice of the C57BR/cdJ, C57BL/6J, B10.BR/SgSnJ, C58/J, AKR/J, C57L/J, and RF/J strains. Cysts were largely found in the leptomeninges, adjacent to the posterior horn and the lateral or anterior columns. The cysts consisted of a central whorled mass of keratinized cells surrounded by polygonal epithelial cells; some of these cells contained keratohyaline granules. Basal cells were absent. The presence of cysts did not correlate with the H-2^k or H-2^b haplotypes of the mouse.

Abstract.

The p73 gene encodes a protein structurally and functionally homologous to TP53, and maps to chromosomal band 1p36.33, where loss of heterozygosity has been observed in up to 90% of oligodendrogliomas and in 10–25% of diffuse astrocytomas. We assessed the methylation status of the CpG islands in the promoter region of the p73 gene by methylation-specific PCR in 117 glioma biopsies. Methylation was detected in 5 out of 28 (18%) glioblastomas and in 4/26 (15%) anaplastic oligodendrogliomas (WHO grade III) but not in grade II oligodendrogliomas, low-grade diffuse astrocytomas (grade II), and anaplastic astrocytomas (grade III). To assess whether p73 methylation leads to loss of expression, we carried out reverse transcription-PCR and methylation-specific PCR in 10 glioblastoma cell lines. Two lines (U87MG and T98G) showed p73 methylation. U87MG had no unmethylated p73 (complete methylation), and showed loss of expression. T98G had methylated and unmethylated p73 (partial methylation), and retained p73 expression. A third cell line (LN-308) showed loss of p73 expression without p73 methylation. These results suggest that complete p73 methylation is associated with loss of expression, but that additional mechanisms may cause loss of p73 expression. Analysis of a polymorphic site in exon 2 further showed that p73 was mono-allelically expressed in 6 out of 7 primary gliomas with heterozygous GC/TA polymorphism.

We present a case of Alexander’s disease (AD) in a Bernese mountain dog. The male dog had a clinical history of tremors of the hind legs and posterior weakness, which deteriorated rapidly to posterior paresis and tetraparesis. After a disease duration of 4 weeks the dog was euthanatized at 13 weeks of age. Macroscopically the brain showed moderate enlargement of the lateral ventricles. Histologically there was marked proliferation of astrocytes with abnormally large cell bodies in the white matter of the brain and the white and gray matter of the spinal cord. In these regions numerous round, club-shaped, or elongated deposits consistent with Rosenthal fibers (RFs) were found. They were most prominent in perivascular, subependymal, and subpial areas where they were perpendicularly arranged. Additionally there was considerable loss of myelin. Immunohistologically the RFs were positive for glial fibrillary acidic protein and αB-crystallin. Unter the electron microscope the RFs were found to be located in the cell bodies and processes of astrocytes and appeared as osmiophilic irregularly formed bodies of uneven size with distinct borders that were tightly associated with glial filaments. The histological, immunohistochemical, and ultrastructural findings of this canine case of AD are identical with those in human cases.