Brain research. Molecular brain research
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Brain Res. Mol. Brain Res. · May 1998
Comparative StudyIschemia-induced CA1 neuronal death is preceded by elevated FosB and Jun expression and reduced NGFI-A and JunB levels.
Alterations in levels of the immediate-early gene (IEG) proteins Fos, FosB, DeltaFosB, Jun, JunB, JunD, and NGFI-A were investigated in rat hippocampus by immunohistochemistry 2, 12, 24, and 48 h after forebrain ischemia. Transient global ischemia of 20 min, produced by four vessel occlusion (4-VO), elicited different patterns of IEG expression in vulnerable CA1 and more resilient CA3 neurons. Cell counts revealed that except for JunD and NGFI-A, immunoreactivity for all examined IEGs was initially elevated by forebrain ischemia in both CA1 and CA3 hippocampal subfields. ⋯ Given that JunB can inhibit the transactivating properties of Jun, decreased JunB levels may contribute to the apoptotic death of CA1 neurons by enhancing the transcriptional regulating activity of Jun. Also notable at 48 h was the complete loss of constitutive NGFI-A expression from CA1 neurons of ischemic animals. These findings suggest that persistent elevations in FosB and Jun expression, concurrent with reductions in JunB and NGFI-A levels, contribute to the apoptotic death of CA1 neurons after forebrain ischemia.
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Brain Res. Mol. Brain Res. · Mar 1998
Proopiomelanocortin (POMC) mRNA expression: distribution and region-specific down-regulation by chronic morphine in female guinea pig hypothalamus.
There is compelling evidence that endogenous opioid peptides are regulated by exogenous opiates. Our previous studies have shown that the mu-opioid receptor protein and mRNA are down-regulated in the mediobasal hypothalamus of the female guinea pig following chronic morphine treatment. In addition, electrophysiological studies have shown that hypothalamic beta-endorphin (beta-EP) neurons express mu-opioid receptors that are uncoupled and down-regulated following chronic morphine treatment. ⋯ Overall, the level of POMC mRNA was decreased by 22% in the Arc of morphine-treated guinea pigs as compared with the placebo controls (p < 0.05). This decrease in POMC mRNA expression was even greater in the caudal Arc (28%, p < 0.01) in morphine-treated animals. These results suggested that the biosynthetic activity of POMC neurons is down-regulated with chronic exposure to morphine.
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Brain Res. Mol. Brain Res. · Oct 1997
Islet amyloid polypeptide and calcitonin gene-related peptide expression are upregulated in lumbar dorsal root ganglia after unilateral adjuvant-induced inflammation in the rat paw.
After unilateral adjuvant-induced inflammation, expression of neuropeptides believed to be involved in the inflammatory response, e.g. substance P and calcitonin gene-related peptide (CGRP), is upregulated in innervating sensory neurons. Islet amyloid polypeptide (IAPP) is structurally related to CGRP and constitutively expressed in sensory CGRP-containing neurons; the role of IAPP in sensory neurons is unknown. To examine whether IAPP could play a role in inflammation, IAPP expression in L5 dorsal root ganglion (DRG) and its distribution in the dorsal horn were investigated after unilateral adjuvant-induced inflammation in the rat paw and compared with CGRP, using in situ hybridization and immunocytochemistry. ⋯ At day 3, the higher expression of IAPP and CGRP on the ipsilateral side was accompanied by increased numbers of immunoreactive DRG neurons and fibers in the spinal cord dorsal horn. Largely, expression of IAPP and CGRP seems to be co-ordinately regulated by localized inflammation, although the rapid, but transient, upregulation in DRG neurons of IAPP mRNA expression and the slower, but sustained, upregulation of CGRP mRNA expression may indicate dissociated regulation of the peptides. Thus, IAPP could play a role in the initial phase of localized inflammation.
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Brain Res. Mol. Brain Res. · Oct 1997
Transcriptional activation of human choline acetyltransferase by AP2- and NGF-induced factors.
ChAT (choline acetyltransferase) is the enzyme responsible for acetylcholine synthesis and is specifically expressed in cholinergic neurons. To further characterize the transcriptional regulation of the hCHAT (human ChAT) gene by NGF, we examined the effects upon ChAT promoter activity of a family of transcription factors which are activated by NGF and several extracellular stimuli and encoded by immediate-early genes. These include NGFI-A (Egr1, zif268), NGFI-C (Egr2), Krox-20 and NGFI-B (Nurr77). ⋯ Electrophoretic mobility-shift assays showed that the sequence GCCCGGGGAG (NGFRE) located 1205 bp upstream of the first coding ATG (E1) can bind NGFI-A but not NGFI-C. Several possibilities explaining the observed results are discussed. Finally, transfections of ChAT-CAT reporters including the P1 + P2 region or a minimal ChAT enhancer present in the P2 region in front of a heterologous promoter indicated the presence of a regulatory element which conferred AP2-dependent trans-activation with homologous as well as with heterologous promoter constructs.
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Brain Res. Mol. Brain Res. · Mar 1996
Evidence for different mechanisms of induction of HSP70i: a comparison of cultured rat cortical neurons with astrocytes.
This study is a follow-up of previous work which demonstrated that cultured cortical neurons did not synthesize HSP70i immediately after heat stress when compared with cultured cortical astrocytes. We have extended the period of observation for HSP70i induction of cultured cortical neurons and astrocytes up to 24 h after heat stress. Cultured rat cortical neurons derived from 16-day-old fetal rats respond differently to heat stress than cultured rat astrocytes derived from newborn rats. ⋯ In addition most small neurons did not synthesize HSP70i after heat shock. This difference in induction of HSP70i may be secondary to localization and activation of HSF-1 but not HSF-2. Neuronal susceptibility to injury may be related to the delayed induction of HSP70i and also the possible failure of newly synthesized HSP70i to translocate into the nucleus.