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Anabolic-androgenic steroid induced alterations in choline acetyltransferase messenger RNA levels of spinal cord motoneurons in the male rat.

The effect of chronic supraphysiological doses of anabolic-androgenic steroids, such as those illegally used by recreational, amateur and professional athletes to increase muscle mass and strength, on motoneurons has not been established. The choline acetyltransferase activity levels of perineal muscles in the male rat are modulated by plasma testosterone levels. These muscles are innervated by the sexually dimorphic motoneurons of the spinal nucleus of the bulbocavernosus. Since the primary source of choline acetyltransferase in muscle is motoneuronal, testosterone may modulate perineal muscle choline acetyltransferase activity by regulating choline acetyltransferase messenger RNA levels in motoneurons. The purpose of this study was to determine if choline acetyltransferase messenger RNA levels in cervical and lumbar spinal motoneurons are affected by chronic (four weeks) changes of plasma testosterone levels in the adult male rat. Using in situ hybridization, choline acetyltransferase messenger RNA levels were analysed in four motor columns: the spinal nucleus of the bulbocavernosus, the retrodorsal lateral nucleus of the lumbar spinal cord, and the lateral motor columns of the cervical and lumbar spinal cords. Chronic exposure to supraphysiological levels of testosterone (five- to ten-times physiologic levels) significantly increased choline acetyltransferase messenger RNA in all four motor columns. Subsequent to castration, choline acetyltransferase messenger RNA levels decreased in motoneurons of the spinal nucleus of the bulbocavernosus and the retrodorsal lateral nucleus. This observation suggests that the decrease in choline acetyltransferase activity levels of muscles innervated by spinal nucleus of the bulbocavernosus motoneurons may be due to changes in choline acetyltransferase protein levels. Indeed, testosterone replacement therapy of castrated males prevented the decline of choline acetyltransferase messenger RNA levels in motoneurons. The results of this study demonstrate that anabolic-androgenic steroids can affect the levels of specific messenger RNAs in motoneuron populations throughout the spinal cord suggesting that motoneuronal characteristics are modulated by circulating anabolic-androgenic steroid levels regardless of the purported "androgen sensitivity" of the specific neuromuscular system.

Anabolic Agents↗

Regulation of messenger RNA stability in mouse erythroleukemia cells.

The decay rates of several messenger RNA species were determined in mouse erythroleukemia cells. The t1/2 values for the actin and tubulin mRNAs were 16 to 26 hours and about seven hours, respectively. The globin mRNA, and two mRNA species subject to translation repression, the P40 and P21 mRNAs, were about as stable as the ribosomal RNA. A stable tubulin mRNA component also appeared to be present in the cells. Exposure of the cells to dimethylsulfoxide for 48 hours led to considerable increases in the rates of decay of all but the globin mRNA. The induction of erythroid differentiation caused by the drug appears to lead to activation of a mRNA-degradation process that affects individual species to different degrees. The newly synthesized actin and tubulin mRNAs lost their poly(A) rather rapidly. This was accompanied by accumulation of poly(A)-deficient mRNA chains, particularly in the case of actin mRNA. The steady-state distribution of mRNA components, determined by Northern blot analysis, also showed that the actin mRNA and one tubulin mRNA species have a high proportion of poly(A)-deficient molecules. The globin, P40 and P21 mRNAs showed little tendency to lose their poly(A) sequence. The steady-state globin and P40 mRNAs also had a low proportion of chains depleted of poly(A). For all five species, the proportions of poly(A)-deficient chains in newly synthesized mRNA were about the same in uninduced and induced cells, in spite of the large decreases in mRNA stability in the induced cells. The lack of correlation between tendency to lose poly(A) and rate of mRNA decay, and the large accumulation of poly(A)-deficient molecules in the cases of the actin and tubulin mRNAs suggest that the stability of mRNA is not determined solely by the presence of poly(A) on the RNA chains. The behavior of the untranslated species in induced and uninduced cells also fails to support the notion of a relationship between translation and mRNA decay.

Actins↗

Complex of transfer-messenger RNA and elongation factor Tu. Unexpected modes of interaction.

Transfer-messenger RNA (tmRNA) is a stable RNA in bacteria of 360 +/- 40 nucleotides that can be charged with alanine and can function as both tRNA and mRNA. Ribosomes that are stalled either in a coding region of mRNA or at the 3' end of an mRNA fragment lacking a stop codon are rescued by replacing their mRNA for tmRNA. Here we demonstrate that the interaction of tmRNA with the elongation factor Tu shows unexpected features. Deacylated tmRNA can form a complex with either EF-Tu.GDP or EF-Tu.GTP, the association constants are about one order of magnitude smaller than that of an Ala-tRNA.EF-Tu.GTP complex. tmRNA as well as Ala-tmRNA can be efficiently cross-linked with EF-Tu.GDP using a zero-length cross-link. The efficiency of cross-linking in the case of deacylated tmRNA does not depend on an intact CCA-3' end and is about the same, regardless whether protein mixtures such as the post-ribosomal supernatant (S100 enzymes) or purified EF-Tu are present. Two cross-linking sites with EF-Tu.GDP have been identified that are located outside the tRNA part of tmRNA, indicating an unusual interaction of tmRNA with EF-Tu.GDP.

Cell-Free System↗

Overexpression of DM20 messenger RNA in two brothers with Pelizaeus-Merzbacher disease.

Pelizaeus-Merzbacher disease is a rare, sex-linked recessive, dysmyelinating disease of the central nervous system that has been associated with mutations in the myelin proteolipid protein (PLP) gene. Only 25% of patients studied with Pelizaeus-Merzbacher disease have exonic mutations in this gene, the underlying cause of the disease in the remaining patients is unknown. The PLP gene encodes two major alternatively spliced transcripts called PLP and DM20. PLP messenger RNA is specifically expressed in central nervous system tissue, whereas DM20 messenger RNA is found in central nervous system, cardiac, and other tissues. We studied cultured skin fibroblasts from 2 brothers with Pelizaeus-Merzbacher disease who exhibited no detectable exonic mutation of the PLP gene. Examination of RNA from these cells showed that the level of DM20 messenger RNA is elevated sixfold relative to male control skin fibroblasts. An unrelated female carrier, also with no detectable exonic mutation, showed a threefold increase in DM20 messenger RNA in cultured skin fibroblasts. Our findings suggest that in some patients, Pelizaeus-Merzbacher disease is caused by overexpression of PLP gene transcripts, and that in these families a 50% increase of DM20 messenger RNA in females, relative to the increase in affected males, can identify a female carrier.

Adolescent↗

Alteration of Coding Properties of Polysome-Associated Messenger RNA in Potato Tuber Slices during Aging.

Kinetics of polysome formation, translational capacity, and coding properties of polysome-associated messenger RNA were investigated in potato tuber tissue discs during aging. Polysome content rapidly increased immediately after slicing from 14% of total ribosomes in freshly sliced discs to 55% within 12 hours of aging. The amount of polysomal RNA also increased 5-fold during this period. Translational capacity of polysome-associated messenger RNA increased in parallel with the increase in content of polysomal RNA of the tissue discs when measured in a wheat germ cell-free system. Analysis of the in vitro translation products by sodium dodecyl sulfate-polyacrylamide gel electrophoresis revealed that the majority of polypeptides coded by the messenger RNA did not vary greatly during the period of rapid polysome formation. Three types of messenger RNA were found to change in amount during that period: those which appeared only after aging, those which disappeared during aging, and those which disappeared early but reappeared later in the aging period.

Journal Article↗

The human forebrain has discrete estrogen receptor alpha messenger RNA expression: high levels in the amygdaloid complex.

Estrogen is considered to play an important role in neuropsychiatric disorders and the estrogen receptors mediate the action of the hormone. In the present study, the messenger RNA expression pattern of the estrogen receptor alpha subtype was identified in the post mortem human brain. High stringent in situ hybridization histochemistry was performed using a riboprobe specific for the estrogen receptor alpha subtype. The human brain was mainly characterized by abundant estrogen receptor alpha messenger RNA expression in the amygdala and hypothalamus, but labeling (lower) was also found in the extended sublenticular amygdala, cerebral cortex, and hippocampus. In the amygdala, the estrogen receptor alpha messenger RNA was preferentially expressed in medially-localized nuclei suggesting that estrogen regulates distinct human amygdala-mediated functions. The Cynomologous monkey brain was also examined in the present study and a similar distribution of the estrogen receptor alpha messenger RNA signal was observed in the human and monkey brain. However, the primate expression pattern differed in part from the known distribution in the rat. The current results show that estrogen receptor alpha messenger RNA is expressed in discrete areas of the human brain not only related to neuroendocrine function, but also emotion, memory, and cognition, which is consistent with the hypothesized involvement of estrogen in schizophrenia, affective disorders, and Alzheimers disease.

Adolescent↗

Apolipoprotein B messenger RNA editing: insights into the molecular regulation of post-transcriptional cytidine deamination.

A site-specific cytidine deamination (cytidine to uridine) in nuclear apolipoprotein B messenger RNA creates a translational stop codon that produces apolipoprotein B48. This process is mediated by an enzyme composed of distinct subunits, including apolipoprotein B messenger RNA editing enzyme catalytic polypeptide-1 and additional complementation factors. The apolipoprotein B messenger RNA editing enzyme catalytic polypeptide-1 is expressed ubiquitously in the rat, but is largely confined to the small intestine in humans and rabbits. By contrast, complementation activity is present in tissues that neither express nor edit apolipoprotein B messenger RNA.

APOBEC-1 Deaminase↗

Biologic activity and quantification of messenger RNA coding for human chorionic somatomammotropin in normal and intrauterine growth--retarded pregnancies.

Total ribonucleic acid (RNA) from human placentas obtained from normal and intrauterine growth--retarded (IUGR) pregnancies was translated in a reticulocyte cell--free system. Synthesis of human chorionic somatomammotropin (hCS) was estimated as a ratio of specific immunoprecipitated protein over total newly synthesized proteins. There is no significant difference between in vitro hCS synthesis directed by placental RNA from normal and IUGR pregnancies. Measurements of messenger RNA sequences coding for hCS, with a hCS complementary DNA probe, indicated that the hCS messenger RNA (mRNA) concentrations were similar for both groups. Low plasma hCS levels in pregnancies associated with growth-retarded fetuses can be explained by their significantly lower placental weights which correlate with their total RNA content. The total capacity of in vitro hCS production per placenta is significantly lower in this type of abnormal pregnancy. There is a good parallelism between the amount of hCS mRNA, its biologic activity tested in a cell-free system, and the secretion of hCS in the maternal circulation. These data suggest that there is no basic intracellular disturbance in hCS synthesis in placentas from fetal growth--retarded pregnancies.

Female↗

L-DOPA produces strong induction of c-fos messenger RNA in dopamine-denervated cortical and striatal areas of the common marmoset.

Common marmosets (Callithrix jacchus) with near-complete unilateral 6-hydroxydopamine denervation of the dopaminergic input received a single injection of saline or L-DOPA (15mg/kg plus 6.25mg/kg benserazide). Using in situ hybridization, the effects of these treatments on c-fos messenger RNA expression in the cerebral cortex, the striatal complex and the external layer of the pallidum were studied. Moreover, receptor autoradiography was used to determine the levels of dopamine D(1) and D(2) receptors in these areas. In the cerebral cortex, animals treated with L-DOPA displayed a high expression of c-fos messenger RNA restricted to the dopamine-denervated hemisphere. No changes in the levels of cortical D(1) and D(2) receptors were found in the dopamine-denervated hemisphere. L-DOPA treatment also induced a strong expression of c-fos messenger RNA in the striatal complex in the dopamine-denervated hemisphere. The levels of striatal D(2), but not D(1), receptors were increased in the dopamine-denervated hemisphere. In the external pallidum, the major terminal region for D(2) dopamine receptor-containing striatal projection neurons, L-DOPA treatment induced c-fos messenger RNA expression in both the intact and the dopamine-denervated hemispheres.Thus, using c-fos messenger RNA as a biochemical marker of postsynaptic neuronal activation, these results provide evidence that near-complete dopamine depletion causes a profound supersensitization to L-DOPA treatment in the cerebral cortex and in the striatal complex, but not in the external layer of the pallidum, of the primate brain. The cortical response may be unique to the primate brain, but c-fos messenger RNA activation within the striatum has also been reported in the rodent. The effects of L-DOPA probably depend both on a direct activation of supersensitized dopamine receptors by dopamine produced in the few remaining, but hyperactive, dopaminergic nerve terminals and in serotonergic nerve terminals, as well as on indirect actions of L-DOPA related to activation of circuitries connecting cerebral cortex and basal ganglia structures. These results provide novel information on the mechanisms underlying L-DOPA's action in the cerebral cortex, striatum and external pallidum in a primate model of Parkinson's disease.

Animals↗

Effects of two calcium channel blockers on messenger RNA expression of endothelin-1 and nitric oxide synthase in cardiovascular tissue of hypertensive rats.

OBJECTIVE: The aim of this study was to investigate the effects of calcium channel blockers on messenger RNA expression of endothelin-1 and endothelial-type nitric oxide synthase in the cardiovascular tissue of stroke-prone spontaneously hypertensive rats (SHRSP). MATERIALS AND METHODS: The calcium channel blocker nilvadipine (1.0 or 3.2 mg/kg per day) was subcutaneously administered to two groups of SHRSP, from 4 or 8 weeks of age, for 8 weeks and 4 weeks, respectively. For comparison, nifedipine (3.2 mg/kg per day) was similarly administered to SHRSP from 4 weeks of age for 8 weeks. Kidney, heart, aorta and brain tissue samples were obtained when the rats were 12 weeks old. Messenger RNA expression of endothelin-1 and endothelial-type nitric oxide synthase was determined by reverse transcription-polymerase chain reaction followed by Southern blotting and a ribonuclease protection assay, respectively. Results were compared with those in untreated SHRSP and Wistar-Kyoto rats at 12 weeks of age. RESULTS: Both nilvadipine and nifedipine significantly decreased blood pressure in SHRSP. Although there were no changes in the weights of the kidney and brain, there was a significant decrease in the weight of the left ventricle of the groups treated with nilvadipine (1.0 mg/kg per day: mean +/- SEM 0.282 +/- 0.003 g; 3.2 mg/kg per day: 0.269 +/- 0.005 g) and nifedipine (1 mg/kg/day: 0.281 +/- 0.012 g) for 8 weeks compared with untreated SHRSP (0.301 +/- 0.004 g). Endothelin-1 messenger RNA expression, which was significantly increased by about twofold in the kidney, heart and brain of SHRSP compared with Wistar-Kyoto rats, was normalized by both calcium blockers. Endothelin-1 messenger RNA expression, which was decreased in the aorta of SHRSP, was further decreased by both calcium blockers. While there was no significant difference in endothelial-type nitric oxide synthase messenger RNA expression in the kidney, heart and aorta between the untreated SHRSP and Wistar-Kyoto rats, expression in the aorta was significantly increased in the group treated with these calcium blockers for 8 weeks from 4 weeks of age. CONCLUSIONS: These results suggest that, in addition to their potent antihypertensive effects, calcium channel blockers may exhibit cardiovasculoprotective and renoprotective effects by modifying mRNA expression of endothelin-1 and endothelial-type nitric oxide synthase in tissue.

Animals↗

Dopamine D1 receptor modulation of glutamate receptor messenger RNA levels in the neocortex and neostriatum of unilaterally 6-hydroxydopamine-lesioned rats.

The effect of treatment with the D1 dopamine receptor agonist SKF 38393 on the expression of metabotropic glutamate receptor 1, 3, 4 and 5 receptor subtypes and of the glutamate N-methyl-D-aspartate ionotropic receptor subunits NRI, NR2A and NR2B was analysed using in situ hybridization. We studied the neocortex and neostriatum of normal rats and of rats unilaterally treated with 6-hydroxydopamine, a neurotoxin that, after intracerebral injection into the ventral tegmental area, causes selective degeneration of the ascending dopamine pathway. In the 6-hydroxydopamine-lesioned rats, metabotropic glutamate receptor subtype 3 messenger RNA levels were ipsilaterally increased in the neocortex and neostriatum, while the levels of metabotropic glutamate receptor subtype 4 messenger RNA were bilaterally increased in both regions. When administered to the 6-hydroxydopamine-lesioned rats, the D1 receptor agonist SKF 38393 (3 x 20 mg/kg, s.c.) produced a bilateral decrease in the expression of the metabotropic glutamate receptor subtype 1 and 5 receptor messenger RNA levels in the neocortex and neostriatum. In the neostriatum, SKF 38393 attenuated the ipsilateral increase in the expression of striatal metabotropic glutamate receptor subtype 3 messenger RNA produced by the 6-hydroxydopamine lesion. Furthermore, SKF 38393 produced a bilateral decrease in the levels of NRI receptor subunit messenger RNA and, in contrast, an increase in the striatal NR2B messenger RNA levels. All of these effects were abolished by the D1 receptor antagonist SCH 23360. These results indicate a differential D1 receptor-mediated modulation of the expression of some glutamate receptor subtypes in the neostriatum and neocortex, in agreement with the idea of a functional coupling between dopamine and excitatory amino acid systems in both regions. Thus, pharmacological targeting of excitatory amino acid systems could provide alternative or complementary treatment strategies for diseases involving dopaminergic systems in the striatum (e.g., Parkinson's disease) and cortex (e.g., schizophrenia).

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗

Glucocorticoid effect on the level of corticotropin messenger RNA activity in rat pituitary.

In an attempt to understand the molecular mechanism underlying the depressive effect of glucocorticoids on corticotropin production, the level of corticotropin messenger RNA activity in rat pituitaries was measured with the use of the cell-free protein-synthesizing system derived from wheat germ. The large translation product of corticotropin messenger RNA was identified and quantitated by indirect immunoprecipitation with antibody against corticotropin. The level of corticotropin messenger RNA activity was increased 3- to 6-fold by adrenalectomy. Dexamethasone administration to adrenalectomized rats resulted in a marked suppression of corticotropin messenger RNA activity. Cortisol and corticosterone also exhibited a suppressive effect but were less effective than dexamethasone. In contrast, nonglucocorticoids such as progesterone and aldosterone had no suppressive effect. These results indicate that at least part of the glucocorticoid effect on corticotropin production in the pituitary is exerted at the pretranslational level.

Adrenal Cortex Hormones↗

Subpopulations of mesencephalic dopaminergic neurons express different levels of tyrosine hydroxylase messenger RNA.

Subpopulations of mesencephalic dopamine containing neurons possess different electrophysiological, pharmacological, biochemical, and anatomical properties. In order to determine whether such differences are related to the regulation of tyrosine hydroxylase, the rate limiting enzyme in the synthesis of catecholamines, the regional distribution of tyrosine hydroxylase messenger RNA in these neurons was examined using in situ hybridization histochemistry. In the mouse, labelling for tyrosine hydroxylase messenger RNA associated with individual neurons was significantly less in the lateral substantia nigra pars compacta than in the medial substantia nigra pars compacta and the ventral tegmental area. A similar pattern of labelling was observed in the rat. Labelling for tyrosine hydroxylase messenger RNA was significantly less in the lateral substantia nigra pars compacta than in medial pars compacta (a densely cellular region), the area dorsal to the medial substantia nigra pars compacta (a less cell dense region), and the ventral tegmental area. Differences in levels of labelling for messenger RNA in mesencephalic dopamine neurons were not related to differences in cell size as measured in sections processed for tyrosine hydroxylase immunohistochemistry. The results suggest that tyrosine hydroxylase messenger RNA is differentially regulated in subpopulations of mesencephalic dopamine neurons, supporting the view that these neurons are physiologically distinct.

Afferent Pathways↗

trkB messenger RNA expression in normal human brain and in the substantia nigra of parkinsonian patients: an in situ hybridization study.

trkB is a high-affinity receptor for brain-derived neurotrophic factor, a neurotrophin acting on numerous cells, including dopaminergic neurons. Yet, little is known of its expression in the human brain. We report an in situ hybridization analysis of trkB messenger RNA, encoding the catalytic form of the receptor, in the human brain post mortem. Its expression was found to be widespread but heterogeneous among all the cerebral structures studied, the highest level being found in the cerebral cortex and the cerebellum. A strong but less intense staining was observed in the striatum, nucleus basalis of Meynert, hippocampus, tegmental pedonculopontinus nucleus and substantia nigra pars compacta. Combined immunohistochemistry for tyrosine hydroxylase and in situ hybridization for trkB messenger RNA showed that within the substantia nigra pars compacta a major proportion of dopaminergic neurons expressed trkB messenger RNA. Furthermore, we compared trkB messenger RNA expression in the mesencephalon of six control subjects and five patients with Parkinson's disease, a neurodegenerative disorder characterized by a severe loss of dopaminergic neurons. Despite the fact that the number of trkB messenger RNA-containing neurons was dramatically reduced in the substantia nigra pars compacta and ventral tegmental area of patients with Parkinson's disease, the level of trkB messenger RNA was unchanged in the remaining neurons in diseased brains. These results suggests that trkB is not involved in the process of neuronal death in Parkinson's disease. Furthermore, expression of brain-derived neurotrophic factor high-affinity receptor in patients could allow this neurotrophin to be used to prevent degeneration of surviving neurons at early stages of the disease.

Autoradiography↗

Localization of neuroendocrine secretory protein 55 messenger RNA in the rat brain.

Neuroendocrine secretory protein 55 (NESP55) is a recently characterized secretory protein localized to large dense-core vesicles resembling the class of chromogranins. We investigated the distribution of the messenger RNA encoding for NESP55 in the rat brain by in situ hybridization with specific 35S-labelled oligonucleotides. NESP55 messenger RNA was detected only on neuronal but not glial cells. In the brain, expression of NESP55 messenger RNA was most prominent in several areas throughout the midbrain and brainstem, including the locus coeruleus, the raphe complex and the reticular formation. NESP55 messenger RNA-expressing cells were also found in many areas and nuclei throughout the hypothalamus. Neocortical areas, the hippocampus and the cerebellum were devoid of NESP55 messenger RNA-containing neurons. From this distribution pattern, a significant overlap of NESP55 expression with the noradrenergic, adrenergic and serotonergic transmitter systems was evident. The present study defines, for the first time, the cellular localizaton of NESP55 messenger RNA in the rat brain. The present results provide the basis for future studies defining the as yet obscure function of NESP55.

Animals↗

Messenger RNA in early sea-urchin embryos: cytoplasmic particles.

Three structures containing messenger RNA can be demonstrated in the cytoplasm of early sea-urchin embryos: (i) particles that sediment more slowly than ribosomes and contain newly synthesized DNA-like RNA, (ii) light polyribosomes, which also contain this newly synthesized RNA, and (iii) heavy polyribosomes, which seemingly contain only already existing or "maternal" messenger RNA and account for the bulk of the synthesis of protein.

Animals↗

Determination of actin messenger RNA in cultures of differentiating embryonic chick skeletal muscle.

Cytoplasmic polyadenylylated messenger RNA from differentiated muscle cultures, when incubated in a wheat germ cell-free system, directed the synthesis of a polypeptide indistinguishable from authentic chicken skeletal muscle actin, as judged by mobility on sodium dodecyl sulfate-polyacrylamide gels, tryptic peptide analyses, and biological activity. The synthesis of actin in the cell-free system was used to assay levels of translatable actin mRNA in cultures of fibroblasts, pre- and post-fusion myoblasts, and myoblasts grown under conditions that prevent fusion. In all cases the amount of actin polypeptide synthesized in the cell-free system was proportional to the rate of actin synthesis in the cultures from which the RNA was extracted. It is suggested that actin synthesis is regulated by the actin mRNA content of the cell and that an increase in the cytoplasmic level of translatable actin messenger RNA is mediated by cell fusion rather than by the terminal round of DNA synthesis.

Actins↗

The regional distribution of extracellularly regulated kinase-1 and -2 messenger RNA in the adult rat central nervous system.

It has previously been shown that an intracellular serine/threonine kinase known as extracellularly signal-regulated kinase, also known as microtubule-associated protein kinase, is phosphorylated and activated in response to a range of hormones, growth factors (e.g. nerve growth factor) and neurotransmitters (e.g. N-methyl-D-aspartate) in a variety of cells including neurons. Extracellularly regulated kinases phosphorylate transcription factors, cytoskeletal proteins and enzyme targets. As such they are believed to function in neuronal signal transduction. In situ hybridization histochemistry using synthetic oligonucleotide probes has been used to identify cells in the adult rat central nervous system containing messenger RNAs coding for two isoforms of extracellularly regulated kinase. Extracellularly regulated kinase-2 messenger RNA was observed in many regions including the cerebral cortex, olfactory bulb, hippocampus, amygdala, basal ganglia (except the globus pallidus and endopeduncular nucleus), basal nucleus, thalamus, hypothalamus, brain stem nuclei, cerebellum and neurons in the spinal cord. Extracellularly regulated kinase-1 messenger RNA was confined to fewer regions than extracellularly regulated kinase-2 messenger RNA. Hybridization signals for extracellularly regulated kinase-1 were seen in the olfactory bulb, cortex, regions of the hippocampus, amygdala, nucleus basalis of Maynert, substantia nigra, some hypothalamic and brainstem nuclei and cerebellum, as well as neurons of the spinal cord. Of particular interest, extracellularly regulated kinase-1 messenger RNA was absent from all regions of the basal ganglia and thalamus. Furthermore, extracellularly regulated kinase-1 was almost absent from the CA1 region, whereas extracellularly regulated kinase-2 was present in all neurons of the hippocampus. There were no CNS regions that expressed extracellularly regulated kinase-1 but not extracellularly regulated kinase-2; however, neurons of the dorsal root ganglia showed extracellularly regulated kinase-1 but not extracellularly regulated kinase-2 messenger RNA. Although extracellularly regulated kinase-1 and extracellularly regulated kinase-2 expression was selectively neuronal in the brain, extracellularly regulated kinase-1 messenger RNA was localized to glia in the spinal cord. The distinct cellular distribution of individual extracellularly regulated kinases in the adult rat CNS suggests that they play unique signalling roles.

Animals↗