Biosynthesis of thyrotropin-releasing hormone in organ cultures of the guinea pig median eminence.

Guinea pig median eminence tissue was put into organ culture for periods up to 13 days. The cultured tissue was examined in 3 ways at various ages: a) morphologically, by transmission electron microscopy and light microscopic autoradiography; b) biochemically, by determination of the ability of the cultures to accumulate [3H]L-proline and to incorporate this isotope into [3H]TRH; and c) by bioassay, in which the content of TRH in tissue and culture medium was determined by the ability of extracts of both to release radioimmunoassayable TSH from rat hemi-pituitaries incubated in vitro. It was found that the cultures exhibited a high degree of preservation of ependymal cell morphology and a sustained ability to accumulate [3H]L-proline over the entire 13-day time course. Neuronal elements showed a progressive degeneration with time in culture, and the ability of the culture to produce [3H]TRH was lost concomitantly with the loss in neuronal integrity.

Trophic factors and Alzheimer's disease.

The paper by Butcher and Woolf presents a troubling hypothesis, that neurotrophic factors may be contributory to the pathology of Alzheimer's disease rather than potentially serving as therapeutic agents. Much more experimental work, especially in primates, will be required to tease out the positive and/or negative influences these factors may have on the pathogenesis of the neurodegenerative diseases causing dementias.

The cytoarchitecture and some efferent projections of the centromedian-parafascicular complex in the lesser bushbaby (Galago senegalensis).

The morphology of neurons in the centromedian (CM) and parafascicular (PF) nuclei in the lesser bushbaby (Galago senegalensis) is described in coronal and horizontal brain sections using Golgi-, horseradish peroxidase (HRP)-, and Nissl-staining procedures. The CM contains two types of cells referred to as principal neurons and Golgi type II (like) neurons. Cell bodies of principal neurons are relatively large in cross-sectional area (mean = 130.42 micron2), round to spindle in shape, support short somatic spines, and give rise to three to five primary dendrites. The dendrites branch in a "radiate" pattern and possess numerous appendages consisting of narrow, stalk-supported swellings. The presumed axons of these cells are impregnated only in their initial segments. On the basis of the similarity of principal neuron soma shapes and cross-sectional areas with those of HRP-reactive somata following cortical HRP implantation, it is concluded that at least some of the principal neurons in Galago CM project to somatic sensory-motor cortex. Golgi type II (like) neurons have small (mean = 79.43 micron2), round somata which support several spines and give rise to three to four small-diameter dendrites. The dendrites are infrequently branched, sinuous in their courses, and give rise to complex appendages and beaded processes. However, the axons of these cells could not be seen to ramify in the immediate vicinity of the dendritic field or soma, and there is considerable overlap in the cross-sectional areas of Golgi type II (like) neurons seen in Golgi preparations and HRP-stained cells following cortical implant of HRP pellets. Consequently, although Golgi type II (like) cells have traits characteristic of classically described intrinsic neurons, a cortical projection of these cells cannot be ruled out by the present study. The parafascicular nucleus contains two groups of large, radiate cells characterized by the presence or absence of somatic spines. Cells with somatic spines also contain numerous appendages on the dendrites. Cells without somatic spines support only a few, isolated, short dendritic appendages. Numerous small cell-bodied neurons are present in Nissl-stained sections of PF; however, cells which resemble Golgi type II neurons were not observed in the PF in the present Golgi-impregnated material. In contrast to the CM, the large cell-bodied neurons in PF were not found to project to somatic sensory-motor cortex in Galago.

Subclassification of neurons in the subthalamic nucleus of the lesser bushbaby (Galago senegalensis): a quantitative Golgi study using principal components analysis.

The morphology of neurons in the subthalamic nucleus (STN) of the lesser bushbaby (Galago senegalensis) is described in coronal brain sections processed by Golgi- and Nissl-staining techniques. Quantitative and statistical methods are used to evaluate (1) soma size and shape, (2) dendritic field size, shape, and branch frequency, (3) the number of dendritic and somatic spines per neuron, and (4) neuron location within the STN. Principal components analysis of these variables suggests that three classes of neurons are present. Two of these classes are considered to be projection cells, referred to as elongate-fusiform and radiate neurons, respectively. Elongatefusiform neurons have somata and dendritic fields which are large in diameter, extremely fusiform in shape, and give rise to few appendages. Somata and dendritic fields of radiate neurons are smaller in diameter, more rounded in shape, and support more spines than the elongate-fusiform neurons. The third class of cells in Galago STN is tentatively identified as consisting of interneurons on the basis of small soma and dendritic field size, thin and varicose dendritic morphology, and the presence of multilobulated dendritic appendages.

An ultrastructural study of methionine sulphoximine-induced glycogen accumulation in astrocytes of the mouse cerebral cortex.

Glycogen distribution in the mouse cerebral cortex was examined with electron microscopy following treatment with the experimental convulsant, methionine sulphoximine (M.S.O.). Both at 24 and 48 h followed administration of M.S.O., accumulation of particulate glycogen was prominent in astrocytes throughout the cerebral cortex. In astrocyte cell bodies and in subpial, pericapillary and perineuronal astrocyte processes the glycogen often completely filled the cytoplasm, crowding the remaining organelles and inclusions. The present findings correlate well with biochemical studies of M.S.O. effects of glutamine synthetase activity and energy metabolism. It is suggested that the glycogen may be derived from glutamate which under normal conditions would be converted to glutamine.

Utility of the apolipoprotein E genotype in the diagnosis of Alzheimer's disease. Alzheimer's Disease Centers Consortium on Apolipoprotein E and Alzheimer's Disease.

BACKGROUND: The epsilon4 allele of the gene encoding apolipoprotein E (APOE) is strongly associated with Alzheimer's disease, but its value in the diagnosis remains uncertain. METHODS: We reviewed clinical diagnoses and diagnoses obtained at autopsy in 2188 patients referred to 1 of 26 Alzheimer's disease centers for evaluation of dementia. The sensitivity and specificity of the clinical diagnosis or the presence of an APOE epsilon4 allele were calculated, with pathologically confirmed Alzheimer's disease used as the standard. The added value of the APOE genotype was estimated with pretest and post-test probabilities from multivariate analyses to generate receiver-operating-characteristic curves plotting sensitivity against the false positive rate. RESULTS: Of the 2188 patients, 1833 were given a clinical diagnosis of Alzheimer's disease, and the diagnosis was confirmed pathologically in 1770 patients at autopsy. Sixty-two percent of patients with clinically diagnosed Alzheimer's disease, as compared with 65 percent of those with pathologically confirmed Alzheimer's disease, had at least one APOE epsilon4 allele. The sensitivity of the clinical diagnosis was 93 percent, and the specificity was 55 percent, whereas the sensitivity and specificity of the APOE epsilon4 allele were 65 and 68 percent, respectively. The addition of information about the APOE genotype increased the overall specificity to 84 percent in patients who met the clinical criteria for Alzheimer's disease, although the sensitivity decreased. The improvement in specificity remained statistically significant in the multivariate analysis after adjustment for differences in age, clinical diagnosis, sex, and center. CONCLUSIONS: APOE genotyping does not provide sufficient sensitivity or specificity to be used alone as a diagnostic test for Alzheimer's disease, but when used in combination with clinical criteria, it improves the specificity of the diagnosis.