By using intrathecal administration of antisense oligodeoxynucleotide (AS-ODN) against preprodynorphin mRNA in rats, we observed that this treatment could block both the formalin-induced behavioral nociceptive responses and the increased expression of dynorphin A (1-8) in the dorsal horn, with the increased expression of c-Fos protein being unchanged. For we have reported that intrathecal administration of AS-ODN against c-fos mRNA blocks the nociceptive responses and both the increased Fos protein and dynorphin A (1-8), the results of the present study suggest that: (1) Nociceptively induced spinal expression of dyorphin and Fos protein is involved in the transmission of nociceptive information at the spinal level and the expression of Fos protein is the up-stream event. (2) dynorphin may act as a pronociceptive, not an antinociceptive, factor in the modulation of the spinal hyperalgesic state.

To investigate the role of immediate-early gene c-fos in sodium selenite-induced apoptosis and its position in a possible cascade of apoptogenic genes, we compared the time-courses of expression for 5 related genes, including c-fos, during the apop- tosis induced by sodium selenite with or without blockage of c-fos expression by adding c-fos antisense oligodeoxynucleotide ( ASO) in cultured cortical neurons. The results showed that: (1) in control experiments without c-fos ASO adding, 0. 5 μmol/ L sodium selenite-induced apoptosis as revealed by electrophoretic and flow cytometric examinations; at the same time, sodium selenite also induced down-regulation of bcl-2 mRNA expression and up-regulations of mRNAs related to bax, c-fos, p53, and acetylcholinesterase (AChE) genes; (2) in similar experimental conditions with c-fos ASO cotreatment, the sodium selenite-in- duced apoptosis was blocked with the up-regulation of p53 expression still emerging as before, while the changes in expressions of bcl-2, bax, AChE genes were reversed at the same time. The results suggest that c-fos ASO could play a protective role upon cortical neurons from suffering apoptosis induced by sodium selenite, and there might exist a cascade of gene expressions with p53 and c-fos genes being regulated upstream and then bcl-2, bax, and AChE genes being regulated downstream.

Objective To find out if the lesion in nucleus basalis of Meynert (nbM) can induce some morphological changes characteristic of Alzheimer's disease.Methods Kainic acid was injected into nbM of the rats, and the behavioral deficiency and the morphological changes in the cortex and hippocampus were observed by methenamine silver staining and electron microscopical examination.Results After 9-15 months of breeding following nbM-lesion, we observed many pathological changes in this animal model, which were characteristic of Alzheimer's disease in human, and especially we could find for the first time the formation of senile plagues after 15-month breeding.Conclusion It is proposed that the degeneration of nbM neurons might be primary and responsible for the pathological changes in other brain tissues in sporadic Alzheimer's disease.

Objective To further investigate the mechanism of nasal secretion closely related to the innervation patterns in nasal mucosa with emphasis on the acetylcholinesterase (AChE)-positive fibers and peptidergic terminals in nasal mucosa as well as trigeminal ganglion (TG) cells.Methods Histochemical demonstration of AChE-positive fibers, immunohistochemical study of the distribution patterns of multiple peptidergic terminals, double labelling of AChE and substance P (SP) and somatostatin (SOM) mRNA in situ hybridization were carried out in nasal mucosa and trigeminal ganglion (TG) in rats. Results AChE-positive terminals were mainly distributed in the mid to posterior one third of septal nasal mucosa, with greater staining density on the walls of small vessels and glands. There were fewer such terminals in turbinate mucosa. Tachykinins-ergic terminals, including substance P(SP)-, neurokinin A (NKA)-, neurokinin B(NKB)- and calcitonin gene-related peptide (CGRP)-ergic terminals, had an extensive localizations in nasal mucosa, involving the following areas: between epithelial cells, submucosa, the walls of small vessels, glands and venous sinusoids in both septal and turbinate nasal mucosa. Septal mucosa had the greater density. There were overlaps in the distribution of these peptidergic terminals. There were also vasoactive intestinal peptide (VIP)-, neuropeptide Y (NPY)- and galanin (GAL)-ergic terminals in nasal mucosa. But no neurotensin (NT)- and somatostatin (SOM)-ergic terminals were found. In situ hybridization revealed SOMmRNA expression in TG cells. AChE and nine neuropeptides existed in the cytoplasms of TG cells. Besides, AChE and SP could exist simultaneously in cytoplasms of TG cells.Conclusions AChE-positive (corresponding to parasympathetic nerves) and peptidergic terminals have different distribution patterns in the nasal mucosa of rats, although an overlap does exist, indicative of their different physiological effects on the regulation of nasal secretion and other functions; AChE and multiple neuropeptides in the cytoplasm of TG cells might play a role in modulating the nasal secretion in response to stimuli in the nasal mucosa.