Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cortical spreading depression (CSD) was induced in male Wistar rats by applying 2 M KCl to the frontal cortex of one hemisphere for 2 h. Saline was applied to the contralateral cortex in the same manner. Following recovery for 24 h, bilateral forebrain ischemia was induced for 6 min, and the animals were permitted to survive for 6 days for assessment of histopathology. The number of necrotic neurons was counted in the cerebral cortex, striatum, and hippocampus of both hemispheres. In separate sets of animals, the effects of KCl application on cortical direct current (DC) potential and regional expression of c-fos mRNA and 72-kDa heat shock protein (hsp72) mRNA were determined. Forebrain ischemia induced selective neuronal necrosis in both hemispheres, but the number of necrotic neurons in the cerebral cortex ipsilateral to the application of KCl was significantly smaller than that in the contralateral cortex (p < 0.02, Wilcoxon signed rank test, n = 7). In the striatum and hippocampus, there were no significant differences in neuronal necrosis between hemispheres. Application of KCl for 2 h induced 11 +/- 2 (mean +/- SD, n = 5) negative deflections of DC potential in the ipsilateral cortex; none were detected in the contralateral cortex. Widespread expression of c-fos mRNA was evident in the ipsilateral cortex, while hsp72 mRNA expression was restricted to the KCl application site. The present results demonstrate that CSD induces tolerance of cortical neurons to ischemia by mechanisms unrelated to hsp72.
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PMID:Spreading depression induces tolerance of cortical neurons to ischemia in rat brain. 767 67

Expression of c-fos mRNA after cortical injury was studied using the in situ hybridization technique. Strong signals for c-fos mRNA were observed immediately after cortical ablation in neurons throughout the cortex ipsilateral to the injury. However, this c-fos mRNA expression was transient and disappeared within 6 h after the injury. When basic fibroblast growth factor (bFGF; 1 micrograms) was applied to the site of ablation, c-fos mRNA signals were observed for a much longer period. Even 24 h after injury, diffuse expression of c-fos mRNA was detected throughout the cortex, being mainly confined to non-neuronal cells. Intraperitoneal injection of MK-801 (3 mg/kg), a non-competitive NMDA receptor antagonist, suppressed the expression of c-fos mRNA after cortical ablation. It suppressed both the immediate and late expression induced by cortical ablation and bFGF. The immediate expression of c-fos in neurons is likely to be due to spreading depression, while neuronal-glial interactions would be involved in the mechanism of late c-fos expression by non-neuronal cells. Our results suggest that induction of c-fos after cortical injury can be modulated by topically applied bFGF and that the N-methyl-D-aspartate (NMDA) receptor is involved in c-fos expression not only caused by injury itself but also induced by injury and bFGF. As the immediate early genes regulate secondary gene responses, the induction of c-fos may contribute to neuronal plasticity and bFGF may enhance its effect.
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PMID:Expression of c-fos mRNA after cortical ablation in rat brain is modulated by basic fibroblast growth factor (bFGF) and the NMDA receptor is involved in c-fos expression. 770 64

In order to study the possible contribution of the substantia nigra (SN) in the positive interaction between dopamine D1 receptor agonists and glutamate antagonists in unilaterally 6-hydroxydopamine (6-OHDA) lesioned rats, the effect of the D1 agonist, SKF 38393, was studied in combination with intranigral infusions of glutamate antagonists of the NMDA (MK 801, CPP) or AMPA (NBQX) type of receptor. Local infusion into the SN of the 6-OHDA lesioned side of MK 801, CPP or NBQX at doses inducing no or minimal behavioral effects significantly increased the turning behavior and the expression of c-fos induced, in the lesioned caudate-putamen (CPu), by a parenteral administration of SKF 38393. The same result was obtained after intra-SN infusion of the GABA agonist, muscimol. High doses of MK 801, CPP or muscimol infused into the SN produced intense contralateral turning per se and induced a sparse c-fos expression in the lesioned CPu which was antagonized by parenteral administration of MK 801. The results indicate that a depression of SN pars reticulata efferent neurons potentiates D1-mediated responses and suggest that this area may play a role in the positive interaction between glutamate antagonists and D1 receptor agonists.
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PMID:Modulation of dopamine D1-mediated turning behavior and striatal c-fos expression by the substantia nigra. 779 18

Levels of mRNAs encoding the proto-oncogene, c-fos, and the 70 kDa stress protein, hsp70, were evaluated in gerbil brain following transient cerebral ischemia of varied duration by in situ and blot hybridization techniques. Blots of total hippocampal RNA obtained after 5 min ischemic insults confirmed a characteristic, transient time course of c-fos expression with a striking elevation within 1 h and a return to control levels by 3 h recirculation. Hsp70 hybridization was significant at 1 h and continued to increase until 3-6 h after the insult. Striking accumulation of c-fos mRNA was detected within 15 min recirculation in dentate granule cells, persisting through 1 h, and a weaker signal was evident in CA1 and CA3 pyramidal neurons of hippocampus, as well as in prepiriform/entorhinal cortex and neocortical regions, during the same interval. Hsp70 hybridization showed an identical distribution at 1 h recirculation. Ischemic insults of 1 min duration resulted in no detectable increase of either mRNA, while 2 min ischemia resulted in changes comparable to those seen after 5 min insults. This common threshold corresponds to the ischemic interval required for energy depletion and resultant failure of intracellular ion homeostasis. In contrast, expression of hsp70 mRNA was not observed under conditions of brief depolarization accompanying cortical or hippocampal spreading depression that were shown to induce c-fos. A delayed component of c-fos mRNA expression was not detected in this model, while persistent hsp70 hybridization, restricted to hippocampal CA1 neurons, was evident at 48 h after either 2 min or 5 min ischemic insults. The parallels in c-fos and hsp70 mRNA expression during early recirculation suggest that overlapping mechanisms triggered following postischemic depolarization contribute to their induction after transient ischemia.
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PMID:Coexpression of c-fos and hsp70 mRNAs in gerbil brain after ischemia: induction threshold, distribution and time course evaluated by in situ hybridization. 785 54

It has been suggested that postsynaptic 5-HT1A receptors in the hippocampus, innervated by 5-HT neurons localized in the median raphe nucleus, mediate adaptive or coping responses to aversive events and that dysfunction of this system is related to symptoms of depression. To test this hypothesis we investigated the expression of c-fos mRNA in animals submitted to immobilization stress. The results showed that c-fos mRNA expression is significantly increased in the dentate gyrus and CA1-CA3 regions of the hippocampus after 30 min of forced restraint, suggesting that this structure is activated during stress. To investigate the role of 5-HT neurotransmission in the hippocampus on adaptation to aversive events we immobilized rats for 2 h and tested them 24 h later in an elevated plus-maze. Our results showed that the previous restraint period decreases exploration of open arms in the maze. This effect was reversed by bilateral microinjection of zimelidine (20 and 100 nmol), a 5-HT re-uptake blocker, or 8-OH-DPAT (3 nmol), a 5-HT1A agonist, into the dorsal hippocampus immediately after restraint. These results are compatible with the idea that postsynaptic 5-HT1A receptors located in the hippocampus participate in the development of tolerance to aversive events.
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PMID:Hippocampal 5-HT receptors and consolidation of stressful memories. 813 41

The effects of neocortical spreading depression (SD) on the expression of immunoreactive c-fos protein were examined within the superficial laminae of trigeminal nucleus caudalis (TNC), a brainstem region processing nociceptive information. KCl was microinjected into the left parietal cortex at 9 min intervals over 1 hr, and SD was detected by a shift in interstitial DC potential within adjacent frontal cortex. The stained cells in lower brainstem and upper cervical spinal cord were counted on both sides after tissues were sectioned (50 microns) and processed for c-fos protein-like immunoreactivity (LI) using a rabbit polyclonal antiserum. C-fos protein-LI was visualized in the ventrolateral TNC, chiefly in laminae I and Ilo and predominantly within spinal segment C1-2 (e.g., -1.5 to -4.5 mm from obex) ipsilaterally. SD significantly increased cell staining within ipsilateral TNC. The ratio of cells in laminae I and Ilo on the left: right sides was 1.32 +/- 0.13 after 1 M KCl, as compared to 1.06 +/- 0.05 in control animals receiving 1 M NaCl instead of KCl microinjections (p < 0.01). The ratio was reduced to an insignificant difference after chronic surgical transection of meningeal afferents and recurrent SD (1.09 +/- 0.11). Pretreatment with intravenous sumatriptan, a 5-HT1-like receptor agonist that selectively blocks meningeal C-fibers and attenuates c-fos protein-LI within TNC after noxious meningeal stimulation, also reduced the ratio to an insignificant difference (1.10 +/- 0.09). Sumatriptan or chronic surgical transection of meningeal afferents, however, did not reduce the ability of KCl microinjections to induce SD. On the other hand, combined hyperoxia and hypercapnia not only reduced the number of evoked SDs from 6.3 +/- 1.0 to 2.5 +/- 1.2 after 0.15 M KCl microinjection, but also significantly (p < 0.01) reduced associated c-fos protein-LI in TNC. These data indicate that multiple neocortical SDs activate cells within TNC. The increase in c-fos protein-LI, observed predominantly ipsilaterally, was probably mediated by SD-induced stimulation of ipsilaterally projecting unmyelinated C-fibers innervating the meninges. If true, this is the first report demonstrating that neurophysiological events within cerebral cortex can activate brainstem regions involved in the processing of nociceptive information via trigeminovascular mechanisms.
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PMID:Neocortical spreading depression provokes the expression of c-fos protein-like immunoreactivity within trigeminal nucleus caudalis via trigeminovascular mechanisms. 838 35

When ingestion of a taste stimulus is paired with internal malaise the animal remembers the taste and rejects its ingestion thereafter. A model of neural substrate for this conditioned taste aversion (CTA) is presented on the basis of our recent experiments. To establish the CTA in rats, 0.01 M saccharin was paired with i.p. injection of 0.15 M LiCl. Behavioral lesion experiments by means of ibotenic acid showed that the parabrachial nucleus (PBN), medial thalamus (MT), and lateral part of the amygdala (LPA) were crucial to establish the CTA. c-fos immunoreactivity studies showed that ingestion of saccharin induced a remarkable activation of the central lateral (cl) subnucleus of the PBN in normal rats, however, rats with the CTA to saccharin showed c-fos neurons in the ventral lateral (vl) subnucleus of the PBN. These findings suggest that the recipient zone for saccharin taste switches from the cl to vl subnuclei after acquisition of a CTA. The taste pathway from the vl subnucleus to the LPA through the MT may be a neural substrate for taste aversion learning. The switching may result from a plastic change involving long-term potentiation and depression due to a convergence of the taste input of saccharin and general visceral information of LiCl injection.
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PMID:Neural mechanisms of taste aversion learning. 838 56

Application of potassium chloride (KCl) to the brain surface elicits spreading depression which leads to a marked induction of the proto-oncogene c-fos in the treated cerebral cortex at the earliest time examined (90 min). High levels of c-fos immunoreactivity are observed up to 6 h after KCl treatment. The areas affected include the cingulate, entorhinal and frontoparietal cortex throughout the treated hemisphere. The c-fos expression preceded an increase in both NGFmRNA and NGF-like protein(s). A maximal increase in c-fos was detected within 3 h, whereas NGFmRNA peaked at 12 h and NGF-like protein(s) reached their maximum level 24 h after KCl application. The most prominent increase in NGFmRNA was measured in the entorhinal cortex (50-fold), but other cortical areas also showed a moderate increase of 2-3-fold. In conclusion, our results provide evidence that increases in c-fos and NGF expression are early adaptive responses following brain injury.
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PMID:Spreading depression induces c-fos-like immunoreactivity and NGF mRNA in the rat cerebral cortex. 844 63

The antioxidant alpha-tocopherol and the weaker antioxidant and prooxidant chemopreventative, beta-carotene have been shown to inhibit tumor cell growth in vivo and in vitro. In some epidemiologic studies their serum levels were demonstrated to be inversely related to the incidence of malignant tumor. We hypothesized two basic pathways triggered by antioxidants and prooxidants, which resulted in the control of tumor cell growth. These included changes in phosphorylation and ultimately transcription. Specifically, the prooxidant beta-carotene treatment produced an oxidative stress resulting in the selective induction of heat shock proteins (hsps). These proteins and other proteins that were possibly oxidized were associated with the increased expression of cyclins (A and D) and increased cdc2 kinase expression. An increase in expression of phosphoproteins, such as p53 (tumor suppressor form) was also discerned. The level of expression for the transcription factor c-fos was reduced. Growth factors that contribute to tumor cell growth were also reduced. Increased DNA fragmentation, depression of proliferation and intracellular calcium levels, the accumulation of tumor cells in G0-->G1, and morphologic changes, were consistent with programmed cell death. Antioxidants such as alpha-tocopherol bound to membrane-associated proteins could inhibit the development of peroxidation products (hydroxyl radicals (.OH)), which attack proteins and modify their function and promote their degradation. Some kinases such as, cdc2 may be increased in activity, which would explain the observed increased expression of tumor suppressor p53, the accumulation of the tumor cells in G1 of the cell cycle and the inhibition of tumor cell proliferation. A reduction in oxidant radicals could also reduce transcription factor products, such as c-myb. Indirectly this result may occur through changes in nuclear translocation (signaling) NF-AT or the Rel-related family of transcription factors, including NF-kB (p50 or p65) or inhibition of immunophilin-calmodulin activity. Although the data remains fragmentary there are common points for control for tumor cell growth resulting from the effects of alpha-tocopherol or beta-carotene treatment. These changes involve phosphorylation and protein expression. Ultimately there is a reduction of important transcription factor protein products, a reduction in response to growth factors, and suppression of cell proliferation, resulting in increased control of the cell cycle.
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PMID:Molecular and biochemical reprogramming of oncogenesis through the activity of prooxidants and antioxidants. 851 52

Cortical brain damage was produced in rats by a focal pulse from a Nd-YAG laser, and evolution of the lesion was evaluated at 30 min, and 2, 8, and 24 h with respect to microvascular perfusion, blood-brain barrier (BBB) permeability, and expression of both the heat-shock/stress protein, hsp72, and the c-fos proto-oncogene transcription factor. A double-labeling fluorescence technique employing intravenously injected Evans blue albumin (EBA) and fluorescein-labeled dextran was used to map and measure BBB damage and microvascular perfusion in fresh frozen brain sections. Hsp72 and c-fos mRNAs were localized by in situ hybridization, and the respective proteins were identified by immunocytochemistry. Parallel sections were stained for glial fibrillary acidic protein and for routine histologic examination. Striking hsp72 mRNA expression was evident by 2 h in an approximately 300 microns wide rim surrounding an area of expanding BBB damage. Increased hsp72 mRNA was observed only in regions of preserved microcirculation, where the hsp72 protein was subsequently localized exclusively in the vasculature at 24 h after the insult. Hsp72-positive endothelial cells spanned the narrow margin between the lesion and histologically normal, glial fibrillary acidic protein (GFAP)-positive cortical tissue. There was no hsp72 expression in the area of subcortically migrating edema fluid. Inductions of c-fos mRNA and Fos protein were not strikingly evident around the focal brain lesion, but were observed transiently throughout the injured hemisphere at 30 min and 2.5 h, respectively, indicating that spreading depression was triggered by the focal injury. These results are in striking contrast to those previously obtained from studies of models of focal ischemic or traumatic brain injury, which are characterized by a complex pattern of glial and neuronal hsp72 expression in the periphery of an infarct, and which suggest that the tightly demarcated lesion produced by the Nd-YAG laser lacks these components of graded injury that are evident following other types of focal brain damage.
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PMID:Heat-shock protein and C-fos expression in focal microvascular brain damage. 853 May 60


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