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PubMed2004

Identification of genes expressed in response to phytoplasma infection in leaves of Prunus armeniaca by messenger RNA differential display.

The messenger RNA (mRNA) differential display technique was applied to the identification and isolation of genes whose transcription was altered in leaves of Prunus armeniaca infected by European stone fruit yellows (ESFY) phytoplasma belonging to ribosomal subgroup 16SrX-B. Four genes whose steady-state levels of expression significantly changed in response to phytoplasma infection were isolated and identified. The results obtained show that two group of genes are affected by phytoplasma infection in apricot leaves. The first group comprises genes that are up-regulated by phytoplasma presence: in particular, a gene encoding the heat-shock protein HSP-70, a gene encoding a metallothionein (MT) and another homologous to the EST 673 cDNA clone of P. armeniaca, whose function was unknown. The other gene identified in our analysis is down-regulated by phytoplasma presence. It encodes a protein having homology to an amino acid transporter of Arabidopsis thaliana. Our findings demonstrate the usefulness of mRNA differential display approach for the detection of plant metabolic pathways affected by phytoplasma infection.

Blotting, Northern↗
PubMed1991

The Xenopus localized messenger RNA An3 may encode an ATP-dependent RNA helicase.

The maternal messenger RNA An3 was originally identified localized to the animal hemisphere of Xenopus laevis oocytes, eggs and early embryos. Xenopus embryos depend on mRNA and protein present in the egg before fertilization (maternal molecules) to provide the information needed for early development. Localization of maternal mRNA gives cells derived from different regions of the egg distinctive capacities for protein synthesis. We show here that An3 mRNA encodes a protein with 74% identity to a protein encoded by the testes-specific mRNA PL10 found in mouse, which is proposed to have RNA helicase activity. Because the gene encoding An3 mRNA is reactivated after gastrulation and remains active throughout embryogenesis, we have examined its distribution in embryonic and adult tissues. Unlike PL10 mRNA, which is primarily restricted to the testes, An3 mRNA is broadly distributed in later development.

Amino Acid Sequence↗
PubMed1980

Mammalian epidermal messenger RNA: identification and characterization of the keratin messengers.

A messenger RNA fraction which directs the synthesis of epidermal keratins and other skin proteins has been isolated from adult guinea pigs and newborn rats, utilizing techniques designed to minimize degradation by endogenous nucleases. During the initial extraction procedures an inhibitor of translation was identified. This inhibitor could be removed by sedimentation of the RNA through cesium chloride. Electrophoresis of the resulting RNA on denaturing agarose/urea gels indicated that, in addition to 18S and 28S ribosomal RNAs, several minor species ranging in size from 10S to 28S were present. This heterogeneous RNA stimulated the incorporation of radioactive amino acids into protein in a reticulocyte lysate system which had an absolute dependence on added mRNA. A fraction of the RNA was retained on oligo(dT)-cellulose, indicating the presence of poly(adenylic acid) sequences. This poly(A)-rich material was considerably enriched for mRNA activity. Analysis of the products of synthesis indicated that proteins which migrated as keratins in 1- and 2-dimensional electrophoretic systems were major translation products of both the unfractionated material and poly(A)-containing fractions. The minimum sedimentation coefficient of keratin mRNAs was found to be 18S, a value consistent with the molecular weight of the keratin polypeptides.

Animals↗
PubMed1986

The 35-nucleotide spliced leader sequence is common to all trypanosome messenger RNA's.

In Trypanosomatidae the messenger RNA's (mRNA's) that code for the variant surface glycoproteins (VSG's), tubulins, calmodulin, and at least a subset of other proteins contain a common 35-nucleotide leader sequence at their 5' ends. Hybrid-arrested in vitro translation has been used to show that all mRNA's in both African and South American trypanosomes contain this 35-nucleotide sequence. Oligonucleotides complementary to this sequence blocked translation of all trypanosome mRNA's in a rabbit reticulocyte lysate system, but did not inhibit translation of mRNA's from other organisms lacking this sequence. An oligonucleotide complementary to the VSG mRNA downstream from the spliced leader sequence arrested only VSG synthesis. Thus, the 35-nucleotide leader sequence is a general feature of all trypanosome mRNA's. The high specificity of oligonucleotides complementary to the spliced leader for their target sequence suggests that analogues permeable to the cell membrane may be useful in the treatment of trypanosomal infections.

Base Sequence↗
PubMed1976

Isolation of rat liver albumin messenger RNA.

Rat liver albumin messenger RNA has been purified to apparent homogeneity by means of polysome immunoprecipitation and poly(U)-Sepharose affinity chromatography. Specific polysomes synthesizing albumin were separated from total liver polysomes through a double antibody technique which allowed isolation of a specific immunoprecipitate. The albumin-polysome immunoprecipitate was dissolved in detergent and the polysomal RNA was separated from protein by sucrose gradient centrifugation. Albumin mRNA was then separated from ribosomal RNA by affinity chromatography through the binding of poly(U)-Sepharose to the polyadenylate 3' terminus of the mRNA. Pure albumin mRNA migrated as an 18 S peak on 85% formamide-containing linear sucrose gradients and as a 22 S peak on 2.5% polyacrylamide gels in sodium dodecyl sulfate. It coded for the translation of authentic liver albumin when added to a heterologous protein-synthesizing cell-free system derived from either rabbit reticulocyte lysates or wheat germ extracts. Translation analysis in reticulocyte lysates indicated that albumin polysomes were purified approximately 9-fold from total liver polysomes, and that albumin mRNA was purified approximately 74-fold from albumin polysomal RNA. The total translation product in the mRNA-dependent wheat germ system, upon addition of the pure mRNA, was identified as authentic albumin by means of gel electrophoresis and tryptic peptide chromatography.

Albumins↗
PubMed1978

Translation and characterization of the fatty acid synthetase messenger RNA.

Fatty acid synthetase messenger RNA was obtained from rat liver polysomal RNA and then injected into Xenopus laevis oocytes. The radioactive fatty acid synthetase protein synthesized in the oocytes was identified by immunoprecipitation with anti-fatty acid synthetase antibody and the immunoprecipitate was then characterized by electrophoresis on sodium dodecyl sulfate-polyacrylamide gel. Co-migration of authentic fatty acid synthetase and the labeled product synthesized in oocytes was observed. Based on sucrose density gradient analysis, the rat liver fatty acid synthetase mRNA has a sedimentation coefficient of approximately 33 S, which agrees with the predicted minimum size necessary to code for the fatty acid synthetase protein. In addition, this mRNA was partially purified with oligo(dT)-cellulose, which indicates that it has a polyadenylate region. The relative in vivo rate of synthesis of fatty acid synthetase and the level of fatty acid synthetase mRNA in liver were also determined during the course of dietary induction of this enzyme. The results indicate that the dietary-induced increase in the level of fatty acid synthetase is probably due to an increased level of the fatty acid synthetase mRNA.

Animals↗
PubMed1975

Demonstration that a mouse immunoglobulin light chain messenger RNA hybridizes exclusively with unique DNA.

32P-labeled light chain messenger RNA was prepared from mouse MOPC 21 myeloma cells. The messenger RNA was hybridized to purified repetitive nuclear DNA and both the hybridized (repetitive 32P-RNA) and nonhybridized (nonrepetitive 32P-RNA) fractions were isolated. Only the nonhybridized RNA gave a T1 ribonuclease fingerprint showing oligonucleotides derived from the variable and constant regions of the light chain messenger RNA. In addition, this fingerprint showed oligonucleotides derived from the untranslated regions of the light chain messenger RNA. The nonrepetitive 32P-RNA was shown to rehybridize only with the unique fraction of total nuclear DNA. The rapidly hybridizing part of the unfractionated 32P-RNA preparation, therefore, is not a component of the light chain messenger RNA itself. Complementary DNA was prepared with reverse transcriptase using unlabeled light chain messenger RNA as template, and the transcripts were fractionated into various size classes. Complementary DNA molecules greater than 900 bases in length hybridized with both the initial messenger RNA and with the nonrepetitive 32P-RNA but failed to hybridize with excess purified repetitive 32P-RNA. The rapidly hybridizing component of the messenger RNA fraction, therefore, does not appear to be transcribed by reverse transcriptase. It is concluded that, under the experimental conditions used, the light chain messenger RNA hybridizes exclusively with unique DNA.

Cell Line↗
PubMed1999

Intraregional variation in expression of serotonin transporter messenger RNA by 5-hydroxytryptamine neurons.

The distribution of the messenger RNA encoding the 5-hydroxytryptamine transporter was investigated in rat brain. 5-Hydroxytryptamine transporter messenger RNA was found exclusively in the B1-B9 cell groups containing the cell bodies of 5-hydroxytryptamine neurons. Combined in situ hybridization and 5-hydroxytryptamine immunocytochemistry demonstrated 5-hydroxytryptamine transporter gene expression in the majority of and exclusively in 5-hydroxytryptamine neurons. Cells differed in their levels of expression of 5-hydroxytryptamine transporter messenger RNA and 5-hydroxytryptamine immunofluorescence, but with a tight correlation between the two parameters. Image analysis of cells from B7, the dorsal raphe nucleus, and B8, the median raphe nucleus, revealed significant differences between groups in the mean cellular level of 5-hydroxytryptamine transporter gene expression. Cells in the ventromedial subdivision of B7 displayed higher levels of expression than cells in B8 or cells in the lateral wings of B7. There was also heterogeneity in the distribution of the cellular levels of expression for two other genes expressed by 5-hydroxytryptamine neurons: l-aromatic amino acid decarboxylase messenger RNA and tryptophan hydroxylase messenger RNA. However, the relative levels of expression of these two genes within the four regions studied differed from that of 5-hydroxytryptamine transporter messenger RNA. These results indicate intraregional differences between 5-hydroxytryptamine neurons with respect to 5-hydroxytryptamine transporter messenger RNA levels. Such differences may account for the differential sensitivity of 5-hydroxytryptamine neurons to cytotoxins.

Animals↗
PubMed1994

Differential regulation of brain-derived neurotrophic factor and type II calcium/calmodulin-dependent protein kinase messenger RNA expression in Alzheimer's disease.

The relative levels of messenger RNA for brain-derived neurotrophic factor and the alpha subunit of calcium/calmodulin-dependent protein kinase type II were examined in hippocampal sections from Alzheimer's diseased and age matched non-diseased brains by in situ hybridization histochemistry. Consistent with previous reports in monkey and rodent, calcium/calmodulin-dependent protein kinase II messenger RNA was prevalent throughout the dentate gyrus, all the principal hippocampal subfields, and adjacent cortical regions. A distribution consistent with the dendritic localization of calcium/calmodulin-dependent protein kinase II was also observed. In contrast, brain-derived neurotrophic factor messenger RNA levels were much lower than calcium/calmodulin-dependent protein kinase II messenger RNA levels and were less widely distributed. Within the hippocampus of Alzheimer's diseased brains, levels of calcium/calmodulin-dependent protein kinase II messenger RNA were increased and levels of brain-derived neurotrophic factor messenger RNA were decreased in comparison with matched controls. These changes were consistently seen in four out of six cases processed for both messenger RNA species and ranged from 150-300% relative to non-diseased brain tissue for calcium/calmodulin-dependent protein kinase II and 20-70% for brain-derived neurotrophic factor. These results suggest that within the Alzheimer's hippocampus an altered program of gene expression is occurring leading to aberrant levels of both calcium/calmodulin-dependent protein kinase II and brain-derived neurotrophic factor messenger RNA. Previous studies of the activity-dependent regulation of these messenger RNA species suggest these results are consistent with a decrease in afferent activity within the Alzheimer's hippocampus.

Aged↗
PubMed1999

Localization of calcium-binding proteins and GABA transporter (GAT-1) messenger RNA in the human subthalamic nucleus.

The distribution of messenger RNA encoding the human GAT-1 (a high-affinity GABA transporter) was investigated in the subthalamic nucleus of 10 neurologically normal human post mortem cases. Further, the distribution of messenger RNA and protein encoding the three neuronally expressed calcium-binding proteins (calbindin D28k, parvalbumin and calretinin) was similarly investigated using in situ hybridization and immunohistochemical techniques. Cellular sites of calbindin D28k, parvalbumin, calretinin and GAT-1 messenger RNA expression were localized using human-specific oligonucleotide probes radiolabelled with [35S]dATP. Sites of protein localization were visualized using specific anti-calbindin D28k, anti-parvalbumin and anti-calretinin antisera. Examination of emulsion-coated tissue sections processed for in situ hybridization revealed an intense signal for GAT-1 messenger RNA within the human subthalamic nucleus, indeed the majority of Methylene Blue-counterstained cells were enriched in this transcript. Further, a marked heterogeneity was noted with regard to the expression of the messenger RNA's encoding the three calcium-binding proteins; this elliptical nucleus was highly enriched in parvalbumin messenger RNA-positive neurons and calretinin mRNA-positive cells but not calbindin messenger RNA-positive cells. Indeed, only an occasional calbindin messenger RNA-positive cell was detected within the mediolateral extent of the nucleus. In marked contrast, numerous parvalbumin messenger RNA-positive cells and calretinin messenger RNA-positive cells were detected and they were topographically distributed; parvalbumin messenger RNA-positive cells were highly enriched in the dorsal subthalamic nucleus extending mediolaterally; calretinin messenger RNA-positive cells were more enriched ventrally although some degree of overlap was apparent. Computer-assisted analysis of the average cross-sectional somatic area of parvalbumin, calretinin and GAT-1 messenger RNA-positive neurons revealed them all to be in the range of 300 microm2. The unique patterns of calcium-binding protein gene expression were similarly reflected at the protein level; an abundance of parvalbumin- and calretinin-immunopositive neurons were observed whereas only occasional intensely-labelled calbindin-immunopositive fibres were seen, no calbindin-immunopositive cells were detected. Single and double labelling studies show that parvalbumin-immunopositive neurons were mainly localized in the dorsal region of the nucleus, and calretinin-immunopositive neurons were mainly localized in the ventral region although there was overlap with double-labelled neurons located in the middle and dorsal regions. The significance of these findings, in particular the expression of GAT-1, a high-affinity GABA uptake protein, for basal ganglia signalling is discussed.

Basal Ganglia↗
PubMed2024

Design and evaluation of antisense sequence length for modified mouse U7 small nuclear RNA to induce efficient pre-messenger RNA splicing modulation in vitro.

Pre-messenger RNA (pre-mRNA) splicing modulation is an attractive approach for investigating the mechanisms of genetic disorders caused by mis-splicing. Previous reports have indicated that a modified U7 small nuclear RNA (U7 snRNA) is a prospective tool for modulating splicing both in vitro and in vivo. To date, very few studies have investigated the role of antisense sequence length in modified U7 snRNA. In this study, we designed a series of antisense sequences with various lengths and evaluated their efficiency in inducing splicing modulation. To express modified U7 snRNAs, we constructed a series of plasmid DNA sequences which codes cytomegalovirus (CMV) enhancer, human U1 promoter, and modified mouse U7 snRNAs with antisense sequences of different lengths. We evaluated in vitro splicing modulation efficiency using a luciferase reporter system for simple and precise evaluation as well as reverse transcription-polymerase chain reaction to monitor splicing patterns. Our in vitro assay findings suggest that antisense sequences of modified mouse U7 snRNAs have an optimal length for efficient splicing modulation, which depends on the target exon. In addition, antisense sequences that were either too long or too short decreased splicing modulation efficiency. To confirm reproducibility, we performed an in vitro assay using two target genes, mouse Fas and mouse Dmd. Together, our data suggests that the antisense sequence length should be optimized for modified mouse U7 snRNAs to induce efficient splicing modulation.

RNA, Small Nuclear↗
PubMed1975

Methylated messenger RNA in mouse kidney.

Polyadenylated messenger RNA from mouse kidney labeled in vivo exhibited a pattern of methylation distinct from that of rRNA and tRNA. After mice were given L-[methyl-3H]methionine, 4% of the polyribosomal RNA label was bound to oligo (dT)-cellulose; 20-24% of orotate- or adenine-labeled polyribosomal RNA eluted in the poly(A)+ RNA fraction under similar conditions. [3H]Methyl radioactivity was not incorporated into low molecular weight (5-5.8 S) rRNA, indicating the extent of nonmethylpurine ring labeling was negligible. [3H]Methyl-labeled poly(A)+ RNA sedimented heterogeneously in sodium dodecyl sulfate containing gradients similarly to poly(A)+ mRNA labeled with [3H]orotic acid. Based on an average molecular length of 2970 nucleotides, renal mRNA was estimated to contain 8.6 methyl moieties per molecule. Analysis of alkaline-hydrolyzed RNA sampled by DEAE-Sephadex-urea chromatography provided estimates of the relative amounts of base and ribose methylation. Although 83% of the [3H]methyl radioactivity in rRNA was in the 2'-0-methylnucleotide fraction, no methylated dinucleotides were found in mRNA. In poly(A)+ mRNA 60% of the [3H]methyl label was in the mononucleotide fraction; the remainder eluted between the trinucleotide and tetranucleotide markers and had a net negative charge between -4 and -5. The larger structure, not yet charcterized, could result from two or three consecutive 2'-0-ribose methylations and is estimated to contain 2.6 methyl residues. Alternatively, the oligonucleotide could be a 5'-terminal methylated nucleotide species containing 5'-phosphate(s) in addition to the 3'-phosphate moiety resulting from alkaline hydrolysis. Either structure could have a role in the processing or translation of mRNA in mammalian cells.

Animals↗
PubMed1995

Developmental expression of alpha 7 neuronal nicotinic receptor messenger RNA in rat sensory cortex and thalamus.

The distribution of alpha 7 messenger RNA expression was characterized in developing rat cortex and thalamus. Northern blot analysis of neonatal and adult cortex revealed a single messenger RNA transcript of 5.7 kb. Using in situ hybridization with both full length and short 35S-labeled alpha 7 riboprobes, a distinct transient expression of messenger RNA within sensory cortex and thalamus, during early postnatal development, was observed. alpha 7 transcripts were expressed in low levels as early as embryonic day 13 in the ventricular zone of the neocortex, and as early as embryonic day 15 in the thalamic neuroepithelium. A marked increase in messenger RNA levels was observed during the late prenatal period in both sensory and non-sensory regions of the cortex and thalamus. Moderate to high levels of messenger RNA were maintained into the first postnatal week, followed by a decline into adulthood. alpha 7 messenger RNA expression was significantly higher in the anterodorsal, lateral dorsal, ventral posterior medial and ventral posterior lateral thalamic nuclei of postnatal day 7 pups than in adult brains. Expression of messenger RNA within dorsal lateral geniculate, ventral lateral geniculate and medial geniculate did not show a significant reduction with age. Within the developing cortex, messenger RNA expression delineated the primary somatosensory, auditory and visual cortices in a unique laminar pattern that was consistently and significantly higher than in the adult in superficial layer VI. Higher levels of expression were also observed in retrosplenial cortex at postnatal day 7 than in the adult. Tangential sections through postnatal day 7 cortex revealed low levels of alpha 7 messenger RNA expression delineating the primary sensory areas in layer IV, corresponding to acetylcholinesterase-labeled thalamocortical afferents. However, these sensory areas exhibited higher levels of alpha 7 messenger RNA expression and were more clearly defined in layer VI, but not by acetylcholinesterase staining. The distribution of alpha 7 messenger RNA within the developing thalamocortical system parallels the distribution of alpha-bungarotoxin binding sites and suggests that the receptor is localized on both thalamic cells and their cortical target neurons. This transient and distinct pattern of distribution of the alpha 7 neuronal nicotinic receptor, which coincides with the major phase of thalamocortical development, suggests that it may play a functional role in the development of cortical circuitry.

Acetylcholinesterase↗
PubMed1977

Purification of a putative precursor of globin messenger RNA from mouse nucleated erythroid cells.

Nucleated erythroid cells were incubated for 10 min in the presence of [5-3H]uridine, and the total RNA was isolated by three different extraction procedures. RNA containing globin messenger RNA sequences was purified from other cellular RNAs by selective hybridization to globin complementary DNA cellulose. Depending upon the extraction procedure employed, 0.4-0.6% of the radioactively-labeled total cellular RNA applied to the column annealed to globin complementary DNA cellulose. The annealed RNA was treated with formaldehyde and analyzed by formaldehyde/polyacrylamide gel electrophoresis. Mature globin mRNA and an RNA migrating at approximately 15 S were observed. No globin mRNA containing sequences larger than 20 S were present. The 15S RNA was partially resolved from mature globin mRNA by neutral sucrose density gradient centrifugation. The RNA isolated from the heavy region of this gradient migrated as 15 S in the formaldehyde/polyacrylamide gels and retained its ability to quantitatively anneal to globin complementary DNA cellulose. On the basis of these observations, we conclude that nucleated erythroid cells obtained from the spleens of anemic mice have a 15S RNA which contains globin mRNA sequences. The 15S RNA is not an aggregate and is a good candidate for a globin mRNA precursor.

Animals↗
PubMed1990

Cytoskeletal messenger RNA stability in human neocortex: studies in normal aging and in Alzheimer's disease.

Total RNA was extracted from human brain temporal and parietotemporal neocortical grey matter with postmortem intervals (PMI) of up to 13.5 hours. The integrity and rank abundance of heterogeneous nuclear RNA (HnRNA) and messenger RNA (mRNA) were analyzed by Northern gel dot blot hybridization with specific cloned probes of neurobiological interest: the RNA messages for four cytoskeletal components including glial fibrillary acidic protein (GFAP), alpha-tubulin, beta-actin and the human neurofilament light chain (HNF-L) genomic sequence, the Alu repetitive element, the scrapie prion PrP DNA probe and the chromatin condensing agent linker histone H1(0) genomic probe. Our observations indicate that for the cytoskeletal RNA messages studied here: (1) short postmortem intervals (of up to 4.5 hours) had only small effects upon RNA quality in these neocortices, (2) GFAP and HNF-L transcripts were represented at relatively high levels in the cerebral neocortex and (3) each RNA species in normal human brain had both unique and characteristic intracellular levels of abundance and decay kinetics. In the pathological condition, Alzheimer's disease (AD), cells of the temporal and parietotemporal neocortices of afflicted brains showed selective reductions in cytoskeletal RNA pool size which are not attributable to RNA transcript stability.

Adult↗
PubMed1984

Immunoprecipitation of surface antigen precursors from Schistosoma mansoni messenger RNA in vitro translation products.

Messenger RNA has been isolated from adults and eggs of Schistosoma mansoni and translated in vitro in mRNA dependent rabbit reticulocyte lysate. The in vitro translation products have been immunoprecipitated using a wide variety of hyperimmune and infection sera from rabbits, mice and humans. A large number of in vitro translation products are precipitated by these sera, and we have identified a subset of the immunoprecipitated polypeptides which are expressed on the surface of the young schistosomulum. Messenger RNA from both adults and eggs directs the synthesis of these polypeptides suggesting that at least some of the surface proteins of the young schistosomulum are being synthesised throughout the life cycle. cDNA clone banks prepared from adult mRNA will therefore contain the genes for these schistosomulum surface antigens greatly facilitating their isolation.

Animals↗
PubMed1995

Chronic blockade of muscarinic cholinergic receptors by systemic trihexyphenidyl (Artane) administration modulates but does not mediate the dopaminergic regulation of striatal prepropeptide messenger RNA expression.

A striatal dopaminergic denervation leads to changes in the expression of messenger RNA encoding prepropeptides contained in striatal efferent neurons. Such a dopaminergic lesion also abolishes a functional equilibrium between dopaminergic and cholinergic transmissions, generally believed to operate within the neostriatum, which constitutes the theoretical basis for the clinical use of antimuscarinic drugs in extrapyramidal diseases. It is possible, therefore, that changes in prepropeptide messenger RNA expression are mediated by an alteration in cholinergic transmission. To test this hypothesis, we have examined in rats whether trihexyphenidyl, an antimuscarinic drug of wide clinical use, can counteract the changes in preproenkephalin, preprotachykinin and preprodynorphin messenger RNA expression produced by a unilateral 6-hydroxydopamine lesion of substantia nigra dopaminergic neurons. Two weeks after the lesion, trihexyphenidyl was continuously administered through an osmotic minipump (5 mg/day for 15 days) to half of the lesioned and sham-operated rats, the other half receiving the vehicle. Using quantitative in situ hybridization histochemistry, messenger RNAs were analysed at two rostrocaudal levels (anterior and central) of the neostriatum. In parallel, M1 muscarinic receptors were measured by autoradiography of [3H]pirenzepine binding sites. In sham-operated rats, trihexyphenidyl administration produced a significant increase (17-27%) in M1 binding sites. In addition, preproenkephalin messenger RNA levels were decreased (-38%) in the central part, while preprodynorphin messenger RNA levels were significantly increased (+22%) at both striatal levels. In 6-hydroxydopamine-lesioned rats, the expected changes in messenger RNAs were observed when ipsi- versus contralateral side values were compared, but changes were not always detected when comparison was established between values from the dopamine-denervated neostriatum and those from sham-operated rats. The trihexyphenidyl administration in 6-hydroxydopamine-lesioned animals was unable to reproduce the up-regulation of M1 receptors, even in the intact neostriatum. This antimuscarinic treatment further increased preproenkephalin messenger RNA levels in the denervated anterior neostriatum, amplifying the ipsi- versus contralateral difference. It also potentiated the imbalance in preprotachykinin messenger RNA expression, mainly as a result of an increase of preprotachykinin messenger RNA levels in the intact neostriatum. In contrast, trihexyphenidyl treatment by increasing preprodynorphin messenger RNA in both neostriata abolished the ipsi- versus contralateral difference observed in lesioned rats. In conclusion, with the exception of preprodynorphin messenger RNA, trihexyphenidyl treatment was unable to counteract the imbalance in prepropeptide messenger RNA expression produced by a unilateral striatal dopaminergic denervation and even amplified this effect. These results question the neostriatum as the site of action of antimuscarinic drugs in producing their therapeutic effect in extrapyramidal syndromes.

Animals↗