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We aimed to determine quantitatively the fine amino- and carboxyl-terminal structure of A beta peptides deposited in human brain using a set of 12 anti-A beta antibodies that distinguish between terminal modifications including isomerization, stereoisomerization, limited proteolysis, and cyclization. Immunochemical examination of cortical blocks from aged subjects distinguished by their total plaque load and from a young Down's syndrome patient identified the major invariantly deposited species as A beta x-42 (X = 1(D-aspartate) and 3(pyroglutamate) and/or 11(pyroglutamate)). These molecular forms, presumably representing by-products of metabolic intermediates toward degradation, are similar in being resistant to major aminopeptidases. A beta 17-42 ("p3' fragment), a major secreted form of truncated A beta with high insolubility, was found to be a minor one. A possible interpretation for these observations would be that proteolysis of A beta from its amino terminus may limit the rate of A beta catabolism.

Tyrosine phosphorylation in the gerbil hippocampus after a transient ischemia was analyzed by immunoblotting and immunohistochemistry. In control hippocampus, the phosphotyrosine was detected in many proteins of 165 to 10 kDa and the immunostain showed a distinct distribution. The ischemic insult induced various alterations of the phosphotyrosine immunoreactivities in both ischemia-resistant and -vulnerable neurons which were associated with alterations in the expression of 165 to 19 kDa-immunoreactive bands. These results suggest that tyrosine phosphorylation is involved in the ischemic hippocampus to play a role in the development of early and delayed neuronal deaths in CA4 and CA1 neurons, respectively.

The rate of slow axonal transport of soluble proteins in retinal ganglion cells of the rabbit decreased with approximately 25% in aged (6 years) compared to previous estimates in adult (2 years) animals. Immunobinding of calpain to microtiter plates coated with a monoclonal antibody to mu-calpain was used to isolate labelled axonally transported mu-calpain from the nerve extracts. It was found that the distribution of labelled mu-calpain in the retrobulbar optic pathway was similar to the distribution profile of the slowly migrating phase of soluble proteins.

Arginine vasopressin (AVP) neurons were preferentially localized in the dorsomedial part of the suprachiasmatic nucleus (SCN). To know the role of AVP neurons in the SCN, male rats were kept under a normal light-dark cycle (L-D), or under constant darkness (D-D) for 20 days. In L-D condition, AVP levels in the SCN showed the circadian change. In D-D condition, the patterns in AVP levels showed a free-running rhythm, and an about 12-h shift per 20 days. This result suggests that the activity of AVP neurons may be closely associated with the endogenous circadian rhythm of the SCN.

The distribution of vasoactive intestinal peptide (VIP) and peptide histidine isoleucine amide (PHI) was investigated in the canine hypothalamus by immunocytochemistry. VIP- and PHI-like immunoreactive neurons were detected in the magnocellular supraoptic and paraventricular nucleus. These magnocellular VIP- and PHI-producing neurons coexist with vasopressin-like immunoreactivity and send axons to the median eminence and neurohypophysis. These findings may serve as an anatomical basis for studying the function of VIP and PHI on pituitary hormone secretion.

Specific protease-protease inhibitor interactions have been suggested to play a role in the regulation of neurite outgrowth. We have examined the influence of exogenously added specific protease inhibitors on neurite outgrowth in PC12h cell in serum-free defined medium. Of 14 protease inhibitor species examined, only a leupeptin analogue, Ac-Leu-Leu-Nle-al was stimulatory for neurite outgrowth in the presence of nerve growth factor. Leupeptin and soybean trypsin inhibitor which had been reported to induce neurite outgrowth from sensory ganglia and neuroblastoma cells had no effect. These results suggest that an endogenous protease of a new type is involved in restricting neurite outgrowth in PC12h cell.