The current study analyzed NGF protein levels in the brains of patients with Alzheimer's disease (AD) as compared with aged neurologically normal individuals. An established two-site ELISA was used to measure NGF-like immunoreactivity in the hippocampus, superior temporal gyrus, superior frontal gyrus, inferior parietal lobule, frontal and occipital cortical poles, cerebellum, amygdala, putamen, and nucleus basalis of Meynert (nbM). ChAT activity was assayed in adjacent tissue samples. NGF levels were also evaluated in Parkinson's disease for comparison with both AD and age-matched control cases. Regardless of the brain bank (University of Cincinnati, Rush Presbyterian St. Luke's Medical Center in Chicago, or University of Alabama at Birmingham), NGF-like activity was at least moderately increased with AD in virtually every brain region examined except for the nbM, in which significant declines were observed. NGF levels were also increased when compared with age-matched Parkinson's cases (frontal cortex). NGF-like activity was not related to age at onset or disease duration in AD cases, nor did NGF levels correlate with age at death in the control or AD groups. Correlations between ChAT and NGF-like activity across brains varied considerably and were generally not significant. The present findings indicate that AD is characterized by a widespread increase in cortical and subcortical NGF. Although a correlation with ChAT activity was not observed in cortex, the AD-related decline in NGF found in nbM is consistent with the possibility of impaired retrograde transport of NGF to this region.

Rapid axonal transport was studied by several methods in rats with serum glucose levels above 300 mg/dl as a result of treatment with streptozotocin (45–50 mg/kg) 3 days, 1 wk, 4 wk, 8 wk, or 4 mo earlier. With untreated age-matched rats as controls, rapid anterograde axonal transport in the sciatic nerves of diabetic rats appeared entirely normal. Statistically significant differences were never observed between experimental and control nerves in the basal content of acetylcholinesterase (AChE) and dopamine-β-hydroxylase (DBH) activity or in the rate of accumulation of these enzymes proximal or distal to a ligature. Therefore, the basic capacity for rapid anterograde and retrograde axonal transport of proteins was probably unimpaired in the diabetic nerves. The accumulation of labeled glycoproteins proximal to ligatures on the contralateral nerves of the same rats after injection of the L5 dorsal root ganglion with 3H-fucose was likewise normal. However, rats with 1, 4, and 8 wk of diabetes did show reduced accumulation of fucose-labeled protein distal to nerve ligations, indicating a long-lasting abnormality of retrograde axonal transport. Furthermore, this abnormality was reversed by daily insulin treatment during the second half of an 8-wk experimental period. It is therefore unlikely that the depression of retrograde transport reflects direct toxic effects of streptozotocin. We conclude that streptozotocin-induced diabetes leads to: (1) abnormal delay in the turnaround of transported proteins in distal nerve regions, perhaps combined with (2) an abnormal metabolism of glycoproteins. A delayed onset of retrograde transport is consistent with present observations of reduced accumulation of 125I-labeled nerve growth factor (NGF) below a midthigh ligature on the sciatic nerve after injection of this protein into the hindfoot of rats with 3–5 wk of diabetes. Further work on the factors controlling rapid retrograde transport of proteins in diabetic nerve is warranted.

No abstract

No abstract

No abstract

Studies were done to characterize the bladder dysfunction associated with diabetes mellitus and to distinguish between changes occurring from increased diuresis and autonomic neuropathy. Four experimental conditions were compared: control, 4-wk-streptozocin-induced diabetes, sucrose feeding (diuretic), and galactose feeding (diuretic and sugar alcohol). A 10-fold increase in urine output and 25-50% increases in bladder weight, protein content, and DNA content were observed in all noncontrol treatment groups. Compliance properties were studied by measuring the intravesicular pressure as the bladder was infused with buffer in vitro. All treated bladders exhibited a reduction in plateau pressure and an increase in fluid capacity. Thus, diuresis results in an increased bladder size, which correlates with an alteration of compliance properties. Nervous system control in anesthetized rats was examined by monitoring contractions as the bladder was infused with buffer. Three distinct patterns of response were observed: normal, diabetic, and diuretic (galactose and sucrose treatments). The difference between responses in diuretic and diabetic animals suggests the presence of a diabetes-induced alteration in nerve regulation of the bladder. Reserpine pretreatment of control or diuretic models produced marked changes in the pattern of contractions, whereas pretreatment of diabetic rats had only modest effects. This suggests that diabetic bladders were lacking sympathetic control before the drug treatment. When rats treated for 4 wk with galactose were removed from this diet for 4 wk before testing, the bladders responded similarly to controls. This observation, coupled with the fact that galactose did not produce the same response as diabetes in the in vivo experiment, suggests that the galactose model does not produce irreversible functional neuropathies.

SUMMARY1. Rabbit peroneal nerves were exposed to echothiophate, a quaternary ammonium inhibitor of acetylcholinesterase (AChE), and 217-AO, its tertiary analogue, in an attempt to characterize the localization of the enzyme. Although 217-AO readily inhibited AChE throughout the nerves, echothiophate spared significant amounts unless the tissues had first been homogenized. Notably

The tetrameric form of acetylcholinesterase (AChE) in ReJ/129 dystrophic mice was demonstrated to be absent from endplate-poor regions of skeletal muscle but present in endplate-rich regions. Skeletal muscle secreted normal amounts of this form of AChE. Visceral organs had normal amounts and distribution of the AChE molecular forms. These results suggest that the AChE defect in dystrophic mice is limited to skeletal muscle, and the defect does not reflect an abnormality of AChE synthesis but probably reflects an inability to incorporate the enzyme into skeletal muscle membranes.