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- Kokaia, Zaal, et al.
(författare)
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Regulation of brain-derived neurotrophic factor gene expression after transient middle cerebral artery occlusion with and without brain damage
- 1995
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Ingår i: Experimental Neurology. - : Elsevier BV. - 0014-4886. ; 136:1, s. 73-88
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Tidskriftsartikel (refereegranskat)abstract
- Levels of mRNA for c-fos, nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), TrkB, and TrkC were studied using in situ hybridization in the rat brain at different reperfusion times after unilateral middle cerebral artery occlusion (MCAO). Short-term (15 min) MCAO, which does not cause neuronal death, induced elevated BDNF mRNA expression confined to ipsilateral frontal and cingulate cortices outside the ischemic area. With a longer duration of MCAO (2 h), which leads to cortical infarction, the increase was more marked and elevated BDNF mRNA levels were also detected bilaterally in dentate granule cells and CA1 and CA3 pyramidal neurons. Maximum expression was found after 2 h of reperfusion. At 24 h BDNF mRNA expression had returned to control values. In the ischemic core of the parietal cortex only scattered neurons were expressing high levels of BDNF mRNA after 15 min and 2 h of MCAO. Analysis of different BDNF transcripts showed that MCAO induced a marked increase of exon III mRNA but only small increases of exon I and II mRNAs in cortex and hippocampus. In contrast to BDNF mRNA, elevated expression of c-fos mRNA was observed in the entire ipsilateral cerebral cortex, including the ischemic core, after both 15 min and 2 h of MCAO. Two hours of MCAO also induced transient, bilateral increases of NGF and TrkB mRNA levels and a decrease of NT-3 mRNA expression, confined to dentate granule cells. The upregulation of BDNF mRNA expression in cortical neurons after MCAO is probably triggered by glutamate through a spreading depression-like mechanism. The lack of response of the BDNF gene in the ischemic core may be due to suppression of signal transduction or transcription factor synthesis caused by the ischemia. The observed pattern of gene expression after MCAO agrees well with a neuroprotective role of BDNF in cortical neurons. However, elevated levels of NGF and BDNF protein could also increase synaptic efficacy in the postischemic phase, which may promote epileptogenesis.
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| 2. |
- Li, Zhao-Qi
(författare)
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Mechanisms of secretagogue action in isolated parietal cells
- 1995
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The mechanisms of secretagogue action and various intracellular events in isolated pig and rat gastric parietal cells were investigated. The response to gastrin in aminopyrine accumulation, an index of the acid produced and n·apped by the cells, was ilifferent in pig and rat parietal cells. In pig, gastrin alone stimulated (unaffected by H2 antagonist ranitidine) and potentiated the action of histamine, IBMX, DBcAMP and Sp-cAMP[S]. In rat cells, gastrin alone was ineffective but potentiated the actions of histamine, DBcAMP and Sp-cAMP[S]. The stimulation of aminopyline accumulation by the acetylcholine analogue carbachol, or by gastrin (in pig), was dosedependently inhibited by the protein kinase A inhibitor Rp-cAMP[S]. In rat cells, histamineandDBcAMP-stimulated aminopyrine accumulations were dose-dependently inhibited by the intracellular Ca2+ chelator BAPT A. The basal intracellular cAMP content in pig palietal cells was 3.5-fold higher than that in rat parietal cells. Although IBMX slightly increased cAMP content, it was not enough to increase aminopyrine accumulation in rat. Histamine combined with IBMX increased the cAMP content by 8- to 38-fold. The aminopyrine accumulation, however, was not stimulated further than that observed with histamine-stimulation alone. Gasn·in increased cytosolic free Ca2+ in both pig and rat palietal cell. Basal Ca2+ was reduced by the intracellular Ca2+ chelator BAPTA, and both gasn·in- and carbachol-induced increases in cytosolic free Ca2+ were abolished by the inclusion of BAPT A. Gastrin was as efficient as histamine in inducing the formation of vacuolar/canalicular spaces in the parietal cells, i.e., inducing a secretion-associated morphology. Ranitidine abolished histamine- but not gasn·in-induced morphological n·ansformation. In the presence of BAPTA, the morphological transformations induced by either gastrin, the cAMP analogues DBcAMP or Sp-cAMP[S] were completely abolished. It is concluded that: I) gastrin has a direct action on the parietal cells; 2) species difference of gastrin action seems to be related to different basal cAMP contents; 3) Ca2+. dependent morphological transformation is essential for aminopyrine accumulation; and 4) a threshold level of either Ca2+ or cAMP seems to be required for the stimulation by the other second messenger.
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