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PubMedDate not supplied

Electro-magnetic fields in the home environment (color TV, computer monitor, microwave oven, cellular phone, etc) as potential contributing factors for the induction of oncogen C-fos Ab1, oncogen C-fos Ab2, integrin alpha 5 beta 1 and development of cancer, as well as effects of microwave on amino acid composition of food and living human brain.

The effects, on normal human subjects, of 3 minutes exposure to electro-magnetic fields (EMFs) emitted from: A) personal computers, B) color television sets, or C) microwave-ovens, or cellular phones were compared by placing the same large sheet of aluminum foil with a square hole or rectangular band-shaped hole at the chest level (or at the side of the head with the cellular phone), with or without grounding the aluminum foil, using the Bi-Digital O-Ring Test Dysfunction Localization and Molecular Identification Methods with cancer related substances (i.e., Oncogen C-fos Ab2 and mercury in the cell nucleus, Integrin alpha 5 beta 1 in the cell & nuclear membranes, and disappearance of Acetylcholine) as reference control substances. All the above sources of the EMFs not only induced the following various transitional abnormalities on the EMF entry area, but also induced similar abnormalities at the EMF exit area on the back (where the abnormality was found in the same shape as exposed EMF entry area, and the effect lasted for a shorter time than the entry point of the EMF): A) Exposure of the body at about 50 cm from the monitor of some of the typical personal computers resulted in: A1) decrease in Acetylcholine; A2) appearance of circulatory disturbance with the appearance of Thromboxane B2; A3) short-lasting appearance of Oncogen C-fos Ab2; A4) short-lasting appearance of Oncogen C-fos Ab1, though it lasted longer than C-fos Ab2; A5) no appearance of Integrin alpha 5 beta 1. B) part of the chest was exposed at a distance between 1 meter and up to 3 meters from a color television sized anywhere from 13'' to 21'', resulting in: B1) decrease in Acetylcholine; B2) appearance of circulatory disturbance with the appearance of Thromboxane B2; B3) short-lasting appearance of Oncogen C-fos Ab2; B4) short-lasting appearance of Oncogen C-fos Ab1, though it lasted longer than C-fos Ab2; B5) very short-lasting appearance of Integrin alpha 5 beta 1. C) When body was exposed, at a distance of 0.5m-2 meters, to microwaves emitted as leakage from a small microwave oven (about 2.45 GHz with 450 Watt output), the effects usually lasted about 2 to 3 times the exposure time at the exposed area and 1.6 to 2 times the exposure time at the back of the body at the EMF exit area.(ABSTRACT TRUNCATED AT 400 WORDS)

Acetylcholine↗
PubMed1993

Synergistic increase of phorbol ester-induced c-fos mRNA expression by retinoic acid through stabilization of the c-fos message.

Retinoic acid (RA) has been shown to be able to antagonize or synergize with phorbol 12-myristate 13-acetate (PMA). In contrast to its antagonistic effects on PMA-dependent gene expression, no molecular target or mechanism of synergism has been characterized yet. We now report, that RA synergistically enhances the induction of c-fos, but not c-jun mRNA by PMA in cells whose growth was stimulated by RA alone. The responding cells were hybrids of tumor cell lines whose growth and PMA-dependent c-fos mRNA expression remained unaffected by RA. The increase in PMA-dependent c-fos expression required pretreatment of cells with RA for at least 2-4 h and was achieved at doses as low as 10(-10) M. Nuclear run-on experiments and transient transfection assays using a chimeric reporter gene construct with sequences from the c-fos promoter indicated that RA did not affect PMA-dependent c-fos transcription. Instead, RA stabilized the c-fos message after induction by PMA as assessed by measuring the half-life of c-fos mRNA in actinomycin D-treated cells. This post-transcriptional regulation provides a mechanism whereby RA can synergistically enhance gene expression by PMA.

Dose-Response Relationship, Drug↗
PubMed1993

Costimulation of peripheral blood T cell activation by human endothelial cells. Enhanced IL-2 transcription correlates with increased c-fos synthesis and increased Fos content of AP-1.

Endothelial cells (EC) act as APC for resting PBL in vitro, and may have important roles in vivo in the pathogenesis of allograft rejection and delayed hypersensitivity. We previously reported that human umbilical vein EC provide costimulatory signals to PHA-stimulated PBL via CD2:lymphocyte function-associated Ag-3 and an unidentified ligand pair, resulting in a three- to eight-fold enhancement of IL-2 production. The physiologic relevance of this increase was demonstrated by the proliferative advantage provided by EC to PBL suboptimally stimulated with mAb OKT3. We now report that EC costimulation causes increased levels of IL-2 mRNA as a result of increased IL-2 transcription in PBL. We therefore examined the effects of EC on T cell nuclear factors known to regulate IL-2 transcription, including c-jun and c-fos-two components of the transcription factor AP-1, NFAT, and others. PBL constitutively express c-jun transcripts, and the level of c-jun mRNA is not altered by PHA activation in the absence or presence of EC. In contrast, c-fos mRNA is absent from resting T cells and is induced on PHA activation. EC alone do not induce c-fos mRNA but augment the level of c-fos mRNA in PHA-activated T cells by 3- to 10-fold. This effect is largely independent of the CD2:lymphocyte function-associated Ag-3 pathway. Gel-shift analysis reveals the constitutive presence of nuclear factors in resting PBL that bind to the proximal AP-1 site of the IL-2 promoter and that contain immunoreactive c-Jun but not c-Fos protein. In contrast, AP-1 from PHA-activated cells contains c-Jun and low levels of c-Fos. Strikingly, costimulation with EC results in a dramatic increase (up to 15-fold) in the c-Fos content of AP-1. Levels of other nuclear factors involved in IL-2 regulation were not altered by EC, although NFAT-DNA complexes migrated at a slightly different mobility. In summary, our data suggest that changes in the composition of transcription factor AP-1 is a key molecular mechanism for increasing IL-2 transcription and may underlie the phenomenon of costimulation by EC.

Base Sequence↗
PubMed1987

Isolation and structural analysis of a biologically active chicken c-fos cDNA: identification of evolutionarily conserved domains in fos protein.

To identify functionally important domains in the fos gene product we have studied the evolutionary divergence between chicken and mammalian fos proteins. A cDNA containing the entire chicken c-fos coding region was isolated and its nucleotide sequence determined. The deduced 367-amino acid sequence was compared to that of the mouse and human proteins. This comparison revealed a highly conserved domain (98% homology between mouse and chicken) in the center of the protein (85 amino acids) that coincides with a region known to be indispensible for transforming activity. This highly charged domain presumably contains contact sites for DNA and other proteins as well as a nuclear location signal sequence. Two other regions, that are dispensable for transformation, are also highly conserved and may thus be important for the physiological function of c-fos. These are the N-terminal 88 amino acids (85% homology) and the C-terminal 62 amino acids (92% homology). The C-terminus not only contains a potential DNA-binding Zn-finger structure but is also the least divergent region in the protein at the nucleotide level (92% conservation between chicken and mouse), supporting the hypothesis that mRNA secondary structures in this region may contribute to post-transcriptional regulatory mechanisms. In contrast, the domains between the terminal sequences and the center region of fos protein show considerable divergence (39% and 45% homology, respectively), indicating a minor role, if any, for these sequences. The significance of these conclusions is emphasized by the observation that the chicken c-fos protein, expressed from the cDNA inserted into a retrovirally-derived expression vector, efficiently induces morphological transformation in rat fibroblasts. The chicken c-fos gene product could be identified by immunoprecipitation and in vitro transcription/translation of the isolated cDNA as a protein of Mr approximately 60 K.

Amino Acid Sequence↗
PubMed1998

Synergistic increase in c-fos expression by simultaneous activation of the ras/raf/map kinase- and protein kinase A signaling pathways is mediated by the c-fos AP-1 and SRE sites.

Expression of the c-fos proto-oncogene is induced by numerous stimuli some of which are transmitted through the Ras/Raf/MAP kinase or the cAMP-dependent protein kinase (PKA) pathways. The effect of cell-specific interactions between these pathways on c-fos expression was investigated by exposing quiescent NIH3T3 cells to serum, forskolin, or a combination. Co-stimulation with serum and forskolin resulted in a more than additive increase in c-fos transcription. Synergistic increase in c-fos promoter activity was also observed in transient transfection studies after co-stimulation with serum plus forskolin or co-transfection with c-Raf and PKA expression plasmids. Analysis of the cAMP signaling pathway revealed that the synergy was neither due to an increase in PKA activity nor to Ser-133 phosphorylation/activation of CREB. The activation status of the MAP kinases ERK1 and ERK2 in co-treated cells was comparable to that in serum-treated cells. Co-stimulation with forskolin did not alter the phosphorylation state of Elk-1 compared to serum-induced phosphorylation of Elk-1. Deletion of c-fos promoter elements previously shown to be important for regulation of c-fos expression in response to mitogens indicates a role for SRE and FAP-1 elements.

3T3 Cells↗
PubMed1999

Antisense of c-fos gene attenuates Fos expression in the spinal cord induced by unilateral constriction of the sciatic nerve in the rat.

Sciatic nerve constriction induces expression of c-fos protein in dorsal horn neurons of the spinal cord. Intrathecal administration of c-fos antisense (30 nmol/20 microl) into the lumbar region (L1-L5) 18 h prior to nerve ligation attenuated 80% of Fos-immunoreactivity 90 min after ligation compared to rats infused with c-fos sense or saline. Thus, c-fos antisense may be a useful tool in assessing the role of the c-fos gene in an animal model of neuropathic pain.

Animals↗
PubMed1998

Differential expression of c-fos mRNA and Fos protein in the rat brain after restraint stress or pentylenetetrazol-induced seizures.

1. c-fos mRNA expression and Fos protein expression were investigated by in situ hybridization and immunohistochemistry after 30 min of forced restraint stress or pentylenetetrazol (PTZ; 64 mg/kg, i.p.)-induced seizures. 2. Forced restraint stress and PTZ-induced seizures generated c-fos mRNA expression of distinct intensities, but in similar brain regions, including the hippocampus, the amygdala, the piriform cortex, the paraventricular hypothalamic nucleus, the habenula, and parts of the cerebral cortex. 3. The distribution of Fos-like immunoreactivity induced by stress or seizures only partially overlap. No Fos-like expression was found in the hippocampus or the habenula after restraint stress. Nevertheless, both areas presented Fos-like expression after PTZ-induced seizures. 4. Our results support the suggestion that immediate early gene expression in vivo may exhibit both region- and stimulus-specific expression.

Animals↗
PubMed2002

Amphetamine-induced Fos expression is evident in gamma-aminobutyric acid neurons in the globus pallidus and entopeduncular nucleus in rats treated with intrastriatal c-fos antisense oligodeoxynucleotides.

Double immunostaining for Fos and gamma-aminobutyric acid (GABA) was used in a previously established animal model of striatal dysfunction to examine whether GABA-immunoreactive neurons in the globus pallidus (GP) and entopeduncular nucleus (EP) are activated to express Fos immunoreactivity by intraperitoneal injection of amphetamine. Striatal efferent activity was suppressed by intrastriatal infusions of antisense oligodeoxynucleotide targeted to the messenger RNA of the immediate early gene, c-fos. This suppression produced robust rotational behavior and expression of Fos in the ipsilateral GP and EP following amphetamine challenge. The expression of Fos in the ipsilateral GP and EP following amphetamine challenge is not observed in naïve or control antisense-treated animals. Quantitative analysis revealed that a majority of the amphetamine-activated (Fos-immunoreactive) neurons in the GP and EP express GABA. The present results suggest that inhibitory GABAergic projection neurons within these two nuclei are regulated by inhibitory striatal output and suggests that decreased inhibitory striatal output may contribute to the motor dysfunction observed in patients with Huntington's disease.

Amphetamines↗
PubMed1991

N-methyl-D-aspartate receptor activation in the neostriatum increases c-fos and fos-related antigens selectively in medium-sized neurons.

In the neostriatum a selective loss of neurons occurs following exposure to N-methyl-D-aspartate receptor agonists. One hypothesis emerging from this observation is that an excitotoxic process via N-methyl-D-aspartate receptors may contribute to the pathogenesis of Huntington's disease, which is characterized by the loss of medium-sized neurons. However, whether there is a selective distribution of N-methyl-D-aspartate receptors in specific populations of neostriatal neurons is unknown. In this study the expression of c-fos mRNA and protein was used to examine the response of neostriatal cells to N-methyl-D-aspartate receptor stimulation in the rat. After intrastriatal injection of the N-methyl-D-aspartate receptor agonist, quinolinic acid, an increase in c-fos mRNA concentrations was detected using in situ hybridization and Northern blot analysis. Western blot analysis showed that not only the c-Fos mRNA protein product but also other Fos-related antigens capable of binding to DNA were increased in response to N-methyl-D-aspartate receptor activation. The selectivity of the neuronal response to N-methyl-D-aspartate receptor activation was examined immunohistochemically at the light and ultrastructural levels. Our results indicate that N-methyl-D-aspartate receptor activation by quinolinic acid stimulates medium spiny neurons to increase c-Fos expression; to a lesser extent, medium aspiny interneurons and glial cells also respond. In contrast, negligible change in c-Fos expression is observed in large neurons. These results are consistent with other evidence that medium-sized spiny neurons are preferentially vulnerable to the toxic effects of excitatory amino acids acting at N-methyl-D-aspartate receptors. An additional implication of these findings is that activation of the N-methyl-D-aspartate receptor in medium spiny neurons leads to increased expression of candidate AP-1 transcription factors, thereby coupling the N-methyl-D-aspartate receptor and regulation of gene expression in signal transduction processes of the neostriatal medium spiny neuron.

Animals↗
PubMed2000

Effects of antipsychotic drugs on neurotoxicity, expression of fos-like protein and c-fos mRNA in the retrosplenial cortex after administration of dizocilpine.

In this study, we examined the effect of clozapine, olanzapine, risperidone and haloperidol on the neuropathology (i.e. neuronal vacuolization) and the expression of Fos-like protein and c-fos mRNA in the retrosplenial cortex of female Sprague-Dawley rats induced by the NMDA receptor antagonist dizocilpine. Pretreatment (15 min) with clozapine or olanzapine, but not risperidone or haloperidol, blocked the neuronal vacuolization produced by dizocilpine (0.5 mg/kg, s.c.) in the rat retrosplenial cortex in a dose-dependent manner. Furthermore, pretreatment (15 min) with clozapine or olanzapine, but not risperidone or haloperidol, significantly attenuated the expression of Fos-like protein in the retrosplenial cortex induced by dizocilpine (0.5 mg/kg, s.c.) in a dose-dependent manner. The marked expression of c-fos mRNA in the rat retrosplenial cortex induced by the administration of dizocilpine (0.5 mg/kg, s.c.) was significantly attenuated by pretreatment (15 min) with clozapine (10 mg/kg) or olanzapine (10 mg/kg), but not risperidone (10 mg/kg) or haloperidol (10 mg/kg). The present results suggest that pharmacologically relevant doses of clozapine or olanzapine, but not risperidone or haloperidol, block the neuropathological changes and the expression of Fos-like protein and c-fos mRNA in the rat retrosplenial cortex elicited by the administration of dizocilpine. It is possible that the blockade of dizocilpine-induced neuropathological changes by clozapine and olanzapine may be related to the unique antipsychotic actions of these drugs in schizophrenic patients, although this remains to be verified.

Animals↗
PubMed2001

Expression of c-Fos, Fos B, Jun B, and Zif268 transcription factor proteins in rat barrel cortex following apomorphine-evoked whisking behavior.

Apomorphine-evoked expression of transcription factor proteins: c-Fos, Fos B, Jun B, and Zif268 (also named Krox-24, NGFI-A, Egr-1), was investigated in rat somatosensory (barrel) cortex. The effect of the N-methyl-D-aspartate receptor antagonist MK-801 on their expression was also analyzed. Apomorphine is a dopamine receptor agonist, eliciting motor activity, including enhanced whisking leading to the activation of vibrissae representation in the barrel cortex. Rats had their whiskers clipped on one side of the snout. The Zif268 levels were markedly reduced by this procedure alone. In contrast, apomorphine (5.0 mg/kg) evoked marked c-Fos elevation, less pronounced changes in Jun B and Zif268 and no change in Fos B. The greatest apomorphine-evoked c-Fos accumulation was observed in layers IV and V/VI of non-deprived barrel cortex and was not significantly influenced by MK-801 injection at 0.1 mg/kg. A higher dose of MK-801 (1.0 mg/kg) produced abnormalities in locomotor behavior and diminished c-Fos levels on the non-deprived side to the ones observed in the sensory stimulus-deprived cortex. We conclude that the response of the somatosensory cortex is selective with respect to both the gene activated and its cortical layer localization. Furthermore, sensory stimulation provides a major but not the only component to apomorphine-evoked barrel cortex gene activation.

Afferent Pathways↗
PubMed2004

Anxiolytic activity of the MGLU2/3 receptor agonist LY354740 on the elevated plus maze is associated with the suppression of stress-induced c-Fos in the hippocampus and increases in c-Fos induction in several other stress-sensitive brain regions.

LY354740 is a potent and selective agonist for group II metabotropic glutamate (mGlu) receptors, mGlu2 and mGlu3 receptors, with anxiolytic activity in several animal models of anxiety, including the elevated plus maze (EPM) test. Here, we studied neuronal activation in mouse brain after EPM exposure in saline- and LY354740-treated mice using c-Fos immunoreactivity as a marker. The effect of LY354740 on c-Fos expression was also studied in cage control (no EPM) mice. Pretreatment with LY354740 (20 mg/kg, s.c.) produced robust anxiolytic behavior on the EPM. LY354740 administration decreased EPM-induced increases in c-Fos expression in the CA3 of the hippocampus, while having no significant effects on basal c-Fos expression in the hippocampus. LY354740 administration significantly increased c-Fos expression in specific limbic regions, including the lateral division of the central nucleus of the amygdala (CeL), lateral parabrachial nucleus, locus coeruleus, and Edinger-Westphal nucleus, whether or not animals were exposed to the EPM. Moreover, LY354740 administration per se significantly increased c-Fos expression in regions processing sensory information, including the paraventricular and lateral geniculate nucleus of the thalamus as well as the nucleus of the optic tract and superior colliculus. In particular, the suppression of fear-evoked neuronal activity in the hippocampus and drug-induced increases in neuronal activation in the CeL have been previously linked to the anxiolytic effects of clinically effective drugs such as benzodiazepines, and thus may contribute to anxiolytic actions of LY354740 in animal models and human anxiety patients.

Animals↗
PubMed2004

MEK1-dependent delayed expression of Fos-related antigen-1 counteracts c-Fos and p65 NF-kappaB-mediated interleukin-8 transcription in response to cytokines or growth factors.

Binding sites for the dimeric transcription factor activator protein (AP)-1 are found in numerous immunoregulatory and inflammatory genes. The precise mechanisms by which AP-1 activates or represses immune response genes and in particular the roles of individual AP-1 subunits in inflammatory responses are largely unknown. We report here that c-Fos and Fos-related antigen-1 (Fra-1), two inducible components of AP-1, are recruited to the endogenous interleukin (IL)-8 promoter in an IL-1-dependent manner. c-Fos activates IL-8 transcription and synergizes in this effect with p65 NF-kappaB. In contrast, Fra-1 strongly inhibits inducible IL-8 transcription. Fra-1 activation involves its stabilization, ubiquitination, and interaction with histone deacetylase-1. Blockade of MEK1 by PD98059 suppresses c-Fos and Fra-1 expression and, thus, affects two counteractive signals for IL-8 mRNA synthesis simultaneously. This disturbs the inducible recruitment of TATA box-binding protein and RNA polymerase II to the IL-8 promoter. Additional experiments reveal that, in conjunction with p65 NF-kappaB, the MEK1-ERK-dependent synthesis of c-Fos and Fra-1 serves to adjust the overall expression level of IL-8 in response to two of its physiological inducers, IL-1 and epidermal growth factor. Relative to c-Fos, the delayed recruitment of Fra-1 to the IL-8 promoter provides an example how AP-1 subunits may dampen excessive chemokine synthesis.

Cell Line↗
PubMed1994

Lignocaine-induced convulsion does not induce c-fos protein (c-Fos) in rat hippocampus.

Recent studies have shown that proto-oncogene c-fos mRNA is induced in the central nervous system by a variety of stimuli including generalised convulsions. In this study, the expression of c-fos protein (c-Fos) following lignocaine-induced convulsions was examined and compared with that following convulsions induced by non-anesthetic convulsants, such as pentylenetetrazol, kainic acid and electroconvulsive shocks, in rat brain. Administration of 120 mg.kg-1 lignocaine by the intraperitoneal route induced generalised convulsions in all rats examined within 10 min. C-Fos was markedly induced in the piriform cortex and amygdala, and slightly induced in the neocortex and thalamus, while no c-Fos expression was observed in the hippocampus. In contrast, c-Fos expression following generalised convulsions induced by non-anaesthetic convulsants was very marked in the hippocampal region, piriform cortex and amygdala, and extended to the thalamus and neocortex. These results contradict those of previously reported local cerebral metabolic studies using 2-deoxyglucose as a metabolic marker, and suggest that lignocaine-induced convulsions, unlike those induced by non-anaesthetic convulsants, may not cause severe sequelae (plastic changes) in the hippocampus.

Animals↗
PubMed1990

Serum stimulation of the c-fos enhancer induces reversible changes in c-fos chromatin structure.

Transcription of the proto-oncogene c-fos is known to be activated by growth factors in serum and subsequently repressed by the Fos protein. We show that generalized DNase I sensitivity of c-fos chromatin correlates closely with enhancer activity during induction, repression, and superinduction of the c-fos gene. Within 90 s of serum stimulation, proximal DNA sequences on both sides of the enhancer exhibit increased DNase I sensitivity. Within 5 min, elevated DNase I sensitivity spreads to chromatin at the distal 3' end of the c-fos gene. These results suggest that an open state of chromatin is propagated in both directions from the enhancer. The induced alterations in chromatin structure precede the increased transcriptional activity of the c-fos gene, suggesting that these changes in chromatin structure potentiate transcription.

Cell Division↗
PubMed1994

Phenotypic alterations in fos-transgenic mice correlate with changes in Fos/Jun-dependent collagenase type I expression. Regulation of mouse metalloproteinases by carcinogens, tumor promoters, cAMP, and Fos oncoprotein.

Using specific cDNAs isolated from mouse fibroblasts we determined tissue-specific expression of different matrix metalloproteinase genes: both stromelysin-1 and collagenase IV are highly expressed in heart and lung, whereas collagenase I is expressed most abundantly in skeletal muscle, kidney, and bone. High basal level expression of stromelysin-2 is found in heart and kidney. Like in man and rat, the expressions of collagenase I, stromelysin-1, and stromelysin-2 are regulated by the tumor promoter 12-O-tetradecanoyl-phorbol 13-acetate and by UV irradiation, but not by cAMP. In contrast, the expression of the 72-kDa collagenase IV is not affected by either stimuli. We and others have shown previously that under cell culture conditions, the regulation of human collagenase I is regulated by the transcription factor Fos/Jun (AP-1). Here we show that in c-fos transgenic mice transcription of collagenase I is induced in thymus, spleen, and, most dominantly, in bone upon overexpression of Fos. Neither collagenase IV nor stromelysin-1 or stromelysin-2 expression is affected by c-Fos. The sites of induced collagenase I expression correlate with the sites of Fos-induced long-term cellular alterations in transgenic mice including bone remodeling and T cell development. In fact, in the developing bone tumors strongly enhanced levels of collagenase I transcripts were detectable. These results identify collagenase I as a Fos-regulated gene in vivo and suggest a possible role for Fos/Jun heterodimers in establishing the pathological phenotype of c-fos transgenic mice.

3T3 Cells↗
PubMed1988

IGF-I increases c-fos expression in FRTL5 rat thyroid cells by activating the c-fos promoter.

We studied the effect of IGF-1 on c-fos mRNA expression in FRTL5 rat thyroid cells. IFG-1, or calf serum, transiently increased c-fos mRNA levels in quiescent FRTL5 cells, with the latter being more potent. This increase was prevented by actinomycin D. FRTL5 cells were stably transfected with the c-fos promoter linked upstream to the reporter gene chloramphenicol acetyl transferase (CAT). Calf serum and IGF-1 increased c-fos promoter activity in a prolonged manner, and to an equal degree. Our data indicate that IGF-1, as well as additional factor(s) in serum, increase c-fos mRNA levels, at least in part, by activation of the c-fos promoter.

Animals↗
PubMed1994

Expression of c-fos mRNA and c-fos protein in neocortical transplants placed into excitotoxin-induced lesions in adult rats.

Using anatomical and electrophysiological methods, previous studies from this laboratory demonstrated that fetal neocortical block transplants placed into the excitotoxically ablated cortex of adult rats can establish functional connections with the host central nervous system. In order to further examine functional integration at the level of genomic activation/molecular signaling systems, transplants were analyzed for the presence of c-fos mRNA and Fos protein-labeled cells following a 20-min exposure of the animal to a novel open-field environment. This behavioral testing paradigm, which previously was shown to induce expression of c-fos mRNA in several brain regions including the sensorimotor cortex, was administered at 3 months after grafting. The transplants were found to express c-fos mRNA as well as c-fos protein following novelty exposure. These labeled cells were distributed primarily along the peripheral margin of the grafts. This study therefore suggests that at least some neurons within transplants become integrated with the host pathways at the level of molecular signal transduction.

Animals↗