Brain research. Molecular brain research
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We examined developmental changes of orexins/hypocretins and their receptors (OX1R and OX2R) in the rat hypothalamus from postnatal day 0 to 10 weeks, using in situ hybridization histochemistry for the prepro-orexin, OX1R and OX2R mRNAs and immunohistochemistry for orexin-A and orexin-B. The prepro-orexin mRNA was weakly detected in the lateral hypothalamic area (LHA) from days 0 to 15. Orexin-A- and -B-like immunopositive cells and fibers were not detected from days 0 to 10, but they were observed after day 15. ⋯ Next, we examined the effects of milk deprivation and intraperitoneal (i.p.) administration of leptin on the hypothalamic prepro-orexin mRNA in pups. Although 24-h milk deprivation did not affect the level of the prepro-orexin mRNA at days 5 and 10, i.p. administration of leptin from days 0 to 3 caused a significant increase in the prepro-orexin mRNA on days 5 and 10. These results suggest that the development of orexins may be associated with developmental changes such as increase of leptin, weaning, feeding and sleep/wakefulness states.
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Brain Res. Mol. Brain Res. · Apr 2000
Interleukin (IL)-10 inhibits IL-6 production in microglia by preventing activation of NF-kappaB.
The purpose of this study was to determine if interleukin (IL)-10 inhibits lipopolysaccharide (LPS)-induced IL-6 production in microglia by inhibiting activation of nuclear factor-kappaB (NF-kappaB). N13 microglia (a murine microglial cell line) and primary microglia from neonatal mice were cultured in the presence or absence of LPS and increasing amounts of murine IL-10 for 24 h. As predicted, LPS treatment increased supernatant IL-6 concentration in both N13 and primary microglia cultures. ⋯ Pretreatment with IL-10, however, inhibited LPS-induced activation of NF-kappaB. Furthermore, inhibition of NF-kappaB activity with tosyl-Phe-chloromethlyketone (a serine protease inhibitor that prevents degradation of the NF-kappaB-IkappaB complex), completely blocked LPS-induced IL-6 production. These data suggest that IL-10 inhibited IL-6 production in microglia by decreasing the activity of NF-kappaB and, therefore, extend what little is known of the intricate relationship between anti-inflammatory and inflammatory cytokines in the central nervous system.
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Brain Res. Mol. Brain Res. · Mar 2000
Expression of antinociception in response to a signal for shock is blocked after selective downregulation of mu-opioid receptors in the rostral ventromedial medulla.
Prior work has shown that release of endogenous ligands for mu-opioid receptors in the rostral ventromedial medulla (RVM) is critical for the modulation of spinal nociceptive reflexes observed during stress. In the present study, we used antisense oligodeoxynucleotides (AS ODN) to suppress synthesis of mu-opioid receptors in the RVM prior to activating descending antinociceptive systems with a signal for foot shock. Five groups of rats with RVM cannulae were trained with paired or unpaired exposures to white noise (WN) and foot shock. ⋯ Testing of the same animals several days after the ODN injections showed that the attenuating effect on expression of CHA were reversible. These results support the idea that mu-opioid receptors in the RVM are critically involved in mediating expression of hypoalgesia following stress. They also provide further evidence for dissociation in the mechanisms mediating expression of aversive conditional responses.
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Brain Res. Mol. Brain Res. · Mar 2000
NGFI-B and nor1 mRNAs are upregulated in brain reward pathways by drugs of abuse: different effects in Fischer and Lewis rats.
The two inbred Fischer and Lewis rat strains display differences in acquisition of drug self-administration, suggesting genetic factors controlling the vulnerability to drugs of abuse. In this study, we analyzed the effects of acute and chronic cocaine and morphine on mRNAs encoding the NGFI-B/Nur77 family of nuclear orphan receptors in reward pathways in Fischer and Lewis rats. After a single injection of cocaine, a similar upregulation of NGFI-B mRNA in striatal subregions and cortex cinguli was seen in both Fischer and Lewis rats. ⋯ No effect on Nor1 mRNA levels was seen in Fischer rats after chronic treatments. Our results demonstrate different responses in addiction-prone Lewis rats as compared to the less addiction-prone Fischer rats with respect to NGFI-B and Nor1 mRNA regulation after acute and repeated administration of cocaine and morphine. Thus, we suggest that the transcription factors NGFI-B and Nor1 might be involved in the control of behaviors such as sensitized locomotor response, craving and aversion that appears after repeated administration of abused drugs.
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Brain Res. Mol. Brain Res. · Jan 2000
Cell death in regenerating populations of neurons in BDNF mutant mice.
There are two populations of neurons which are continually renewed in the adult, the dentate gyrus granule neurons and the olfactory bulb granule and periglomerular neurons. In the dentate gyrus, a secondary proliferative zone termed the subgranular zone is established along the interface between the dentate gyrus and the hilus where granule cells are born throughout life. Olfactory bulb neurons are generated in the anterior subventricular zone of the lateral ventricle and migrate via the rostral migratory stream to the olfactory bulb. ⋯ However, increased apoptosis was not limited to precursors, as apoptotic cells were also found in the granule cell layer of the dentate gyrus and in the granule and periglomerular layers of the olfactory bulb. The excessive cell death was limited to these populations of neurons as no excessive cell death was detected in other forebrain areas. We conclude that BDNF is essential for the survival of neurons specifically in populations which are continuously being regenerated in the brain.