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Enhanced visuospatial memory following intracerebroventricular administration of nerve growth factor.

The present work assessed the effects of intracerebroventricular injections of rh recombined human nerve growth factor (rh NGF) (5 micrograms/2.5 microl) at postnatal days 12 and 13 upon the development of spatial learning capacities. The treated rats were trained at the age of 22 days to escape onto an invisible platform at a fixed position in space in a Morris navigation task. For half of the subjects, the training position was also cued, a procedure aimed at facilitating escape and at reducing attention to the distant spatial cues. Later, at the age of 6 months, all the rats were trained in a radial-arm maze task. Treatment effects were found in both immature and adult rats. The injection of NGF improved the performance in the Morris navigation task in both training conditions. There was a significant reduction in the escape latency and an increased bias toward the training platform quadrant during probe trials. The most consistent effect was the precocious development of an adult-like spatial memory. In the radial-arm maze, the NGF-treated rats made significantly fewer reentries than vehicle rats and this effect was particularly marked in the treated female rats. Taken together, these experiments reveal that the development and the maintenance of an accurate spatial representation are tightly related to the development of brain structures facilitated by the action of NGF. Moreover, these experiments demonstrate that an acute pharmacological treatment that leads to a transient modification in the choline acetyltransferase activity can induce a behavioral change long after the treatment.

Age Factors↗

[Transfer and expression of rh-SCF gene in human hematopoietic stem/progenitor cells].

OBJECTIVE: To explore the transfer and expression of recombinant human stem cell factor (rh-SCF) gene in human hematopoietic stem/progenitor cell. METHODS: pLXSN-SCF, a recombinant retrovirus vector of soluble human SCF gene, was constructed by recombinant gene technique. The recombinant plasmid was introduced into virus packaging cells psi2 and PA317 by lipofectin-mediated DNA transfection, and PA317/SCF, the recombinant virus producing cell, was obtained by G418 screening [the virus potency was (2.4-8.5) x 10(5) CFU/ml]. Then, human hematopoietic stem/progenitor cells were transfected with PA317/SCF. The transfer and expression of human SCF gene were assayed by PCR, APAAP immunohistochemical staining and chemoluminance-direct ELISA. RESULTS AND CONCLUSION: retrovirus-mediated rh-SCF gene was successfully transferred and expressed in human hematopoietic stem/progenitor cells.

Animals↗

Involvement of leukotriene B4 and platelet-activating factor in cytokine priming of human polymorphonuclear leucocytes.

Recombinant human (rh) tumour necrosis factor (TNF) alpha and rh granulocyte-macrophage colony-stimulating factor (GM-CSF) prime human polymorphonuclear leucocytes (PMN) for increased superoxide anion (O2-) generation and for increased platelet-activating factor (PAF) biosynthesis and leukotriene B4 (LTB4) release. Both PAF and LTB4 are candidate mediators for the enhanced O2- generation in cytokine-primed PMN, since exogenous PAF or LTB4 primes PMN. We measured the generation and release of these mediators and examined their potential roles in cytokine priming using the PAF receptor antagonist, WEB 2086, and the inhibitor of 5-lipo-oxygenase, CGS 8515.rhTNF-alpha or rhGM-CSF, alone, increased PAF levels in PMN, but did not cause PAF release or LTB4 synthesis. N-formylmethionyl-leucyl-phenylalanine (FMLP) stimulated the release of detectable and biologically active amounts of both LTB4 and PAF in primed, but not in non-primed PMN. However, neither blockade of PAF receptors, nor inhibition of LTB4 synthesis influenced the priming of O2- generation by rhTNF-alpha or rhGM-CSF. Simultaneous pretreatment of PMN with WEB 2086 and CGS 8515 also failed to inhibit priming. Our results do not exclude a role for cell-associated PAF in the priming response, but indicate that the release of PAF and LTB4 do not mediate this phenomenon. The ability of cytokines to amplify the production and release of lipids may represent a mechanism to attract and localize the pro-inflammatory actions of stimulated PMN to regions where cytokine levels are also elevated.

Cells, Cultured↗

[Immunoreactive luliberin in the visceral organs of rats].

The distribution of luliberin (luteinizing hormone-releasing hormone, LH-RH) was studied. LH-RH-like factor showing analogous immunochemical and chromatographic properties was detected in the liver, kidneys, duodenum, pancreas, adrenal glands and heart of rats. The concentration of immunoreactive LH-RH in the liver, kidneys, duodenum, pancreas and adrenal glands was nearly equal (5 to 7 pg per mg of methanol extract obtained from acetic acid extract of acetone powder), its concentration in the heart being somewhat lower (2 pg per mg of extract). Only minute amounts of this factor were present in blood cells. Immunoreactive LH-RH found in visceral organs may be of hypothalamic origin or may be synthesized in these organs (in situ).

Adrenal Glands↗