Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “TYROSINE DECARBOXYLASE”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,027 records · Page 57Linked to original sources
PubMed2002

Genetic engineering of mouse embryonic stem cells by Nurr1 enhances differentiation and maturation into dopaminergic neurons.

Nurr1 is a transcription factor critical for the development of midbrain dopaminergic (DA) neurons. This study modified mouse embryonic stem (ES) cells to constitutively express Nurr1 under the elongation factor-1alpha promoter. The Nurr1-expression in ES cells lead to up-regulation of all DA neuronal markers tested, resulting in about a 4- to 5-fold increase in the proportion of DA neurons. In contrast, other neuronal and glial markers were not significantly changed by Nurr1 expression. It was also observed that there was an additional 4-fold increase in the number of DA neurons in Nurr1-expressing clones following treatment with Shh, FGF8 and ascorbic acid. Several lines of evidence suggest that these neurons may represent midbrain DA neuronal phenotypes; firstly, they coexpress midbrain DA markers such as aromatic L-amino acid decarboxylase, calretinin, and dopamine transporter, in addition to tyrosine hydroxylase and secondly, they do not coexpress other neurotransmitters such as GABA or serotonin. Finally, consistent with an increased number of DA neurons, the Nurr1 transduction enhanced the ability of these neurons to produce and release DA in response to membrane depolarization. This study demonstrates an efficient genetic manipulation of ES cells that facilitates differentiation to midbrain DA neurons, and it will serve as a framework of genetic engineering of ES cells by key transcription factor to regulate their cell fate.

Animals↗
PubMedDate not supplied

Neuroendocrine characteristics of human Leydig cell tumours.

The neuroendocrine nature of a subset of Leydig cells has already been established. The present investigation deals with neuroendocrine characteristics of Leydig tumour cells. A number of neuroendocrine and neuronal markers were demonstrated in Leydig cell tumours of 7 men aged 25-41 years. The following substances were immunocytochemically tested in Leydig tumour cells: the monoamine-synthesizing enzymes tyrosine hydroxylase and aromatic L-amino acid decarboxylase, the indoleamine serotonin, the calcium-binding protein parvalbumin, the microtubule associated protein-2, neurofilament protein 200, synaptophysin, neuron specific enolase, substance P and neuronal nitric oxide synthase (NOS). Compared to the normal interstitial cells beyond the tumours, all neoplastic cells showed a significantly weaker immunoreactivity for nerve cell markers as well as for testosterone and cyclic guanosine monophosphate (cGMP), which is usually accumulated by nitric oxide (NO). This provides evidence for a certain dedifferentiation of Leydig tumour cells. However, these results suggest that tumourous development of Leydig cells does not include loss of neuronal phenotype. Moreover, on the assumption that 'neuronal' Leydig cells exist beside 'non-neuronal' ones in normal testicular tissue, we propose the hypothesis that 'neuronal' Leydig cells can transform to tumour cells.

Adult↗
PubMed1993

Parallel up-regulation of catecholamine biosynthetic enzymes by dexamethasone in PC12 cells.

We sought to investigate whether dexamethasone produces a coordinated, time-dependent effect on all enzymes in the catecholamine biosynthetic pathway in PC12 cells. The levels of mRNAs of tyrosine hydroxylase (TH), aromatic L-amino acid decarboxylase (AADC), and dopamine beta-hydroxylase (DBH) were examined at 0, 6, 12, 24, and 48 h after dexamethasone (5 microM) treatment to PC12 cells. The levels of all enzyme mRNAs steadily increased for 24 h, although the increase of AADC mRNA content was slow. The increased mRNA levels of TH and AADC were maintained at 48 h, whereas the level of DBH mRNA was sharply decreased at 48 h. The maximally induced mRNA levels were approximately 5.0-, 2.4-, and 7.0-fold higher than the control levels of TH, AADC, and DBH, respectively. The elevation of enzyme activities was detected later than the increase in levels of mRNAs. The maximal activities of TH, AADC, and DBH were reached between 48 and 72 h with 3.6-, 1.8-, and 8.0-fold increases, respectively. Low, but detectable, phenylethanolamine N-methyltransferase (PNMT) activity was observed in PC12 cells, and dexamethasone increased its activity 5.6-fold at 72 h. The PNMT mRNA was easily detected by northern blot analysis after exposure for 24 h to dexamethasone. The data suggest that, in PC12 cells, dexamethasone up-regulates all catecholamine biosynthetic enzyme genes in a parallel fashion.

Animals↗
PubMed1986

Enterobacter asburiae sp. nov., a new species found in clinical specimens, and reassignment of Erwinia dissolvens and Erwinia nimipressuralis to the genus Enterobacter as Enterobacter dissolvens comb. nov. and Enterobacter nimipressuralis comb. nov.

Enterobacter asburiae sp. nov. is a new species that was formerly referred to as Enteric Group 17 and that consists of 71 strains, 70 of which were isolated from humans. Enterobacter asburiae sp. nov. strains gave positive reactions in tests for methyl red, citrate utilization (Simmons and Christensen's), urea hydrolysis, L-ornithine decarboxylase, growth in KCN, acid and gas production from D-glucose, and acid production from L-arabinose, cellobiose, glycerol (negative in 1 to 2 days, positive in 3 to 7 days), lactose, D-mannitol, alpha-methyl-D-glucoside, salicin, D-sorbitol, sucrose, trehalose, and D-xylose. They gave negative reactions in the Voges-Proskauer test and in tests for indole, H2S production, phenylalanine, L-lysine decarboxylase, motility, gelatin, utilization of malonate, lipase, DNase, tyrosine clearing, acid production from adonitol, D-arabitol, dulcitol, erythritol, i(myo)-inositol, melibiose, and L-rhamnose. They gave variable reactions in tests for L-arginine dihydrolase (25% positive after 2 days) and acid production from raffinose (69% positive after 2 days). Thirty-four Enterobacter asburiae sp. nov. strains were tested for DNA relatedness by the hydroxyapatite method with 32PO4-labeled DNA from the designated type strain (1497-78, ATCC 35953). The strains were 69 to 100% related in 60 degrees C reactions and 63 to 100% related in 75 degrees C reactions. Divergence within related sequences was 0 to 2.5%. Relatedness of Enterobacter asburiae sp. nov. to 84 strains of members of the Enterobacteriaceae was 5 to 63%, with closest relatedness to strains of Enterobacter cloacae, Erwinia dissolvens, Enterobacter taylorae, Enterobacter agglomerans, Erwinia nimipressuralis, and Enterobacter gergoviae. All strains tested were susceptible to gentamicin and sulfdiazine, and most were susceptible to chloramphenicol, colistin, kanamycin, nalidixic acid, carbenicillin and streptomycin. All strains were resistant to ampicillan, cephalothin, and penicillin, and most were resistant or moderately resistant to tetracycline. Enterobacter asburiae sp. nov strains were isolated from a variety of human sources, most prevalent of which were urine (16 strains), respiratory sources (15 strains), stools (12 strains), wounds (11 strains), and blood (7 strains). The clinical significance of Enterobacter aburiae is not known. As a result of this and previous studies, proposals are made to transfer Erwinia dissolvens and Erwinia nimipressuralis to the genus Enterobacter as Enterobacter dissolvens comb. nov. and Enterobacter nimipressuralis comb. nov., respectively.

Adult↗
PubMed1994

Pancreatic tumoral cell line AR42J: an amphicrine model.

AR42J cells derive from azaserine-induced malignant nodules from the rat pancreas. They differ from normal acinar cells for at least three reasons: 1) they proliferate rapidly; 2) they synthesize, store, and secrete digestive enzymes but the regulation of their exocrine function is abnormal, from the emergence of atypical receptors (e.g., cholecystokinin octapeptide type B and pituitary adenylate cyclase-activating polypeptide type I receptors) to unusual inositol phosphate metabolism and cytoskeleton disorganization; and 3) they possess an added neuroendocrine-regulated pathway characterized by voltage-sensitive ionic currents, post-translational processing of peptidic prohormones (and possibly autocriny), and the release of small neurotransmitters (gamma-aminobutyric acid, glycine, and glutamic acid). These amphicrine cells represent, therefore, a cancerous version of the primordial pancreatic ductular epithelium. Dexamethasone favors their differentiation toward the exocrine phenotype. The mitogenic pathway is favored by the occupancy of receptor tyrosine kinases, adenosine 3',5'-cyclic monophosphate, ornithine decarboxylase expression, and Na(+)-H+ exchange. Somatostatin opposes proliferation through protein phosphatases.

Animals↗
PubMedDate not supplied

Theory and practice of nicotinamide trials in pre-type 1 diabetes.

Autoimmune processes are involved in pancreatic beta cell destruction in type 1 diabetes. Autoantibodies including islet cell antibodies (ICA), glutamic acid decarboxylase antibodies (GADA), and antibodies directed against protein tyrosine phosphatase/IA2 (IA2-Ab) appear in the circulation years before clinical onset and permit increasingly precise disease prediction. Increasing knowledge of the pathogenesis of type 1 diabetes in animal models and humans suggests that progression to disease is not inevitable in those with indications of autoimmune processes directed against islet beta cells, and that these processes may prove vulnerable to intervention. The conditions therefore exist for screening and attempted intervention in pre-type 1 diabetes. This review will discuss the theoretical and practical background to a major controlled trial using one of a number of interventions currently under consideration. Nicotinamide, a soluble B group vitamin, has for many years been known to protect beta cells against a variety of noxious stimuli. It is at high doses a free radical scavenger, a potent inhibitor of the enzyme poly (ADP-ribose) polymerase (PARP), and prevents depletion of intracellular NAD. Although its benefits have been marginal or absent in recently diagnosed patients, promising pilot studies have been performed in ICA positive first degree relatives and schoolchildren. No serious side effects have been reported from its use at the doses proposed in man or other species. There is therefore a sound case for submitting this agent to a controlled clinical trial, which, in view of the numbers involved, has necessarily been launched on an international collaborative basis.

Animals↗
PubMed2002

No evidence of autoimmunity in 6-year-old children immunized at birth with recombinant hepatitis B vaccine.

OBJECTIVES: Taking into account that genetic predisposition, marked by human leukocyte antigen (HLA) class I and II genes, augments the probability of developing an autoimmune disorder after a triggering vaccination, as largely debated, we investigated the frequency of autoantibody production after recombinant hepatitis B vaccine (rHBv) in 6-year-old children immunized at birth to evaluate an association between autoimmune disorders and hepatitis B virus vaccination. METHODS: We investigated the presence of autoantibodies in 210 6-year-old children who were immunized at birth with rHBv: 200 showed anti-hepatitis B surface antigen concentrations > or =10 mUI/mL at seroconversion (responders), and 10 were nonresponders. Data were compared with those obtained in 109 unvaccinated children. All participants were screened for the presence of antinuclear antibodies (ANAs), anti-DNA, antimitochondrial, anti-liver/kidney microsomal, antireticulin, anti-smooth muscle (SMA), and antiribosomal antibodies. All participants were also screened for the presence of antithyroid antibodies, such as antithyroglobulin and antiperoxidase, and for antibodies found in type 1 diabetes, such as tyrosine phosphatase (IA-2A) and glutamic acid decarboxylase (GADA). HLA typing was extended to all 10 nonresponders. RESULTS: Autoantibodies were found in 16 of the 200 responders: ANAs were found in 12 (6%), smooth muscle antibodies were found in 4 (2.0%), and antireticulin antibodies and endomysial antibodies were found in 1 girl with ANAs. Antithyroid antibodies, IA-2A, and GADA were not present in any of the participants. No significant difference was found in the frequency of autoantibodies between vaccinated and control children. Three of the 10 nonresponder children were SMA-positive (30% vs 2% of responders); they also carried the supratype HLA-C4AQ0,DRB1*0301,DQB1*02. A family history for autoimmune disorders was present in 3 (18%; 95% confidence interval [CI]: 4.0%-45.6%) of the 16 responder infants with autoantibodies, in 15 (8.4%; 95% CI: 4.6%-13.1%) of responder children without autoantibodies, and in 1 (10%) of the 10 nonsreponder children. CONCLUSIONS: From our data, vaccination with rHBv given during the neonatal period does not seem to increase autoantibody production in a 6-year-old children. Autoantibodies, referred to as natural autoantibodies, can be found in healthy participants, but their significance is unclear. These autoantibodies often cross-react with bacteria or tumor antigens, suggesting their importance in innate immunity. It has been demonstrated in an animal model that self-antigen can promote B-cell accumulation, and that a significant proportion of natural autoantibodies is the product of this self-antigen- dependent process. Consequently, it has been speculated that self-antigens play a positive role in recruiting B cells as a part of innate immunity, but this process carries a potential risk for unregulated growth. Spreading of the immune response is a common theme in organ-specific and systemis autoimmune diseases, and this could be initiated by exogenous agents, in genetically susceptible hosts, owing to molecular mimicry of natural antigen. Moreover, 3 (18%) of the 16 children who had autoantibodies had a family history of autoimmume diseases. Thus, it is apparent that susceptibility to autoimmunity is determined by genetic factors rather than by vaccine challenge. Among all the children considered, only 1 girl (0.5%) developed celiac disease, reflecting the prevalence described in the literature. GADA and IA-2A were not found in our children; this observation is in agreement with data showing that type 1 diabetes risk may not be altered by vaccinations administered during childhood. On the contrary, a high frequency (30%) of autoantibodies, in particular SMA, was observed in the nonresponder children. The 3 SMA-positive children carried the HLA-C4Q0,DRB1*0301,DQB1*02 haplotype, a well-known predisposing factor for autoimmune disorders. On the other hand, the presence of autoantibodies to smooth muscle is known to be common in hepatitis B infection, and, it has been shown that cross-reactive immunity targeting homologous self-protein may partly account for autoantibody production. Although hepatitis B vaccination given during the neonatal period does not increase autoantibody production in 6-year-old immunized children, we deem useful a more prolonged follow-up for these nonresponder children carrying certain HLA haplotypes (such as C4AQ0,DRB1*0301,DQB1*02), particularly because most autoimmune diseases do not develop until later in life.

Autoantibodies↗
PubMed2005

Survival and differentiation of neural progenitor cells derived from embryonic stem cells and transplanted into ischemic brain.

OBJECT: Cell replacement therapy including the use of embryonic stem cells (ESCs) may represent a novel treatment for damage from stroke. In this study, the authors transplanted neural progenitor cells (NPCs) derived from ESCs into ischemic brain and analyzed their survival and differentiation. METHODS: Multipotential NPCs were generated from ESCs by using the stromal cell-derived inducing activity method. These cells could differentiate in vitro into neurons, glia, and oligodendrocytes, thus revealing them to be neural stem cells. The NPCs were then transplanted into ischemic brain. At 2 weeks postischemia, the transplanted cells occupied 18.8 +/-2.5% of the hemispheric area; by 4 weeks postischemia, 26.5 +/- 4% of the hemisphere. At 4 weeks after transplantation, green fluorescent protein (GFP)-positive transplanted cells showed mature neuronal morphological features. The authors also investigated the expression of differentiation markers and various neurotransmitters. Transplanted cells were immunopositive for neuronal nuclei, beta-tubulin-III, and glial fibrillary acidic protein. Of the GFP-positive cells, 33.3 +/-11.5% were positive for glutamate decarboxylase, 13.3 +/- 5.8% for glutamate, 2.1 +/- 2.5% for tyrosine hydroxylase, 1.8 +/- 2% for serotonin, and 0.4 +/- 0.2% for choline acetyltransferase. CONCLUSIONS: The authors confirmed the survival and differentiation of ESC-derived NPCs transplanted into the ischemic brain. Surviving transplanted cells expressed several neural markers and neurotransmitters. These findings indicate that these cells can function in the brain.

Animals↗
PubMed1999

Type 1 diabetes.

Type 1 (insulin-dependent) diabetes occurs worldwide and can appear at any age. The genetic susceptibility is strongly associated with HLA-DQ and DR on chromosome 6, but genetic factors on other chromosomes such as the insulin gene on chromosome 11 and the cytotoxic T-lymphocyte antigen gene on chromosome 2 may modulate disease risk. Numerous studies further support the view that environmental factors are important. Gestational infections may contribute to initiation, whereas later infections may accelerate islet beta-cell autoimmunity. The pathogenesis is strongly related to autoimmunity against the islet beta cells. Markers of autoimmunity include autoantibodies against glutamic acid decarboxylase, insulin, and islet cell antigen-2, a tyrosine phosphatase-like protein. Molecular techniques are used to establish reproducible and precise autoantibody assays, which have been subject to worldwide standardization. The diagnostic sensitivity (40-80%) and specificity (99%) of all three autoantibodies for type 1 diabetes are high, and double or triple positivity among first-degree relatives predicts disease. Combined genetic and antibody testing improved prediction in the general population despite the transient nature of these autoantibodies. Classification of diabetes has also been improved by autoantibody testing and may be used in type 2 diabetes to predict secondary failure and insulin requirement. Islet autoantibodies do not seem to be related to late complications but rather to metabolic control, perhaps because the presence of islet cell autoantibodies marks different residual beta-cell function. Combined genetic and autoantibody screening permit rational approaches to identify subjects for secondary and tertiary intervention trials.

Clinical Laboratory Techniques↗
PubMed2003

Diagnostic value of carboxypeptidase-H autoantibodies in detecting latent autoimmune diabetes in adults.

OBJECTIVE: To investigate the diagnostic value of carboxypeptidase-H (CPH) autoantibodies in Chinese patients with the latent autoimmune diabetes in adults (LADA). METHODS: One hundred and fifty-four Type 1 diabetes, 104 Type 2 diabetes, and 144 healthy people were enrolled. Recombinant human CPH (54 kD) was labeled by in vitro translation with 35S-methionine and used to evaluate autoantibodies to CPH (CPH-Ab). Radioimmunoassay was applied to detect antibodies to glutamic acid decarboxylase (GAD-Ab), intracellular part of protein tyrosine phosphatase-like protein (IA2ic-Ab), and autoantibodies to insulin (IAA). RESULTS: No differences in CPH-Ab prevalence were found among Type 1 diabetic patients (5/154, 3.2%), Type 2 diabetic subjects (6/104, 5.7%),and the healthy controls (3/144, 2.1%). The prevalences of GAD-Ab, IA2ic-Ab, and IAA were 15.4% (16/104), 2.9% (3/104), and 2.3% (1/43), respectively in Type 2 diabetes. All IA2ic-Ab or IAA-positive patients with Type 2 diabetes were GAD-Ab-positive. No GAD-Ab- or IAA-positive subjects were observed in CPH-Ab-positive patients with Type 2 diabetes. CONCLUSION: CPH-Ab may provide some diagnostic value for LADA, and improve the sensitivity in diagnosing LADA in Chinese when combined with GAD-Ab test in Type 2 diabetes.

Adolescent↗
PubMed1991

Susceptibility to ras oncogene transformation is coregulated with signal transduction through growth factor receptors.

The human teratocarcinoma cell line PA-1 was derived from culturing ascites fluid cells from a patient with an ovarian germ line tumor. We previously described a non-neoplastic variant cloned from the PA-1 human teratocarcinoma cell line, clone 6, which at passage 40 was resistant to transformation by activated ras oncogenes. However, these cells could be transformed by a plasmid containing both myc and ras. Another PA-1 cell variant, clone 1, isolated at passage 63 and used 50 passages later becomes tumorigenic in nude mice after transfection with an activated ras oncogene (Tainsky et al., Anticancer Res., 8, 899-914, 1988). We report here that the progression from ras resistance to ras susceptibility occurs in both clone 1 and clone 6 cells during 25 passages in culture. In the presence of epidermal growth factor, transforming growth factor-alpha, and basic fibroblast growth factor, the ras-transformable cells exhibit anchorage independent growth, whereas the ras-resistant cells can not be growth stimulated by these growth factors. Similarly, ornithine decarboxylase (ODC) activity was inducible in ras susceptible and ras transformed cells by these growth factors, but not in the ras resistant cells. These differences are not due to the level and activity of epidermal growth factor receptor or to the level of expression of 25 proto-oncogenes.

Blotting, Northern↗
PubMed1989

Immunohistochemical identification of serotonin and noradrenalin containing structures within the nerve plexuses of rat ileum.

The distribution of 5-hydroxytryptamine (= serotonin = 5-HT) and noradrenalin (NA) in the enteric plexuses of the rat ileum was studied using immunocytochemical techniques. 5-HT-like immunoreactive fibers were observed only in the myenteric plexus, surrounding the ganglionic cells, which are all unreactive. NA-like immunoreactive fibers were present in all layers of the ileum: in the myenteric plexus, they were localized in the nodes, forming a network all round the neuronal perikarya; in the Meissner plexus, positive axons were arranged in a delicate network; submucosal blood vessels were often provided by NA-immunopositive nerve plexus. In the inner circular muscle layer the immunoreactive NA-positive fibers run within nerve bundles mainly parallel with the smooth muscle cells. The 5-HT immunoreactive material was depleted by treatment with reserpine; depletion of NA by 6-hydroxy-dopamine was also observed; on the contrary, no depletion of 5-HT by 5,7-dihydroxytryptamine was obtained. To confirm the validity of these results, specific antibodies to tyrosine hydroxylase (TH) and aromatic 1-aminoacid-decarboxylase (AADC), two enzymes involved in the synthesis of catecholamines, were used. In conclusion these experiments indicate that 5-HT is present, probably as a transmitter, in certain fibres of the rat myenteric plexus, distributed in a way similar to that of NA-containing fibers. However, at variance with NA fibers, 5-HT fibers are not present in other regions of the intestine wall.

5,7-Dihydroxytryptamine↗
PubMed1998

Significant behavioral recovery in Parkinson's disease model by direct intracerebral gene transfer using continuous injection of a plasmid DNA-liposome complex.

As an alternative to virus-mediated gene transfer, we previously demonstrated a simple, safe, and efficient transfer of foreign gene into the central nervous system using continuous injection of a plasmid DNA-cationic liposome complex. To explore whether this approach can be applied to the treatment of certain neurological disorders, we used an experimental model of Parkinson's disease (PD) in the present study. Following continuous injection for 7 days, tyrosine hydroxylase (TH) and aromatic L-amino acid decarboxylase (AADC) genes carried by a bovine papilloma virus-based plasmid vector were efficiently introduced into glial cells in the striatum of 6-hydroxydopamine-lesioned rats. Significant recovery in apomorphine-induced rotational behavior of PD models was obtained by transfection of TH gene and this effect continued for up to 5 weeks after injection. Moreover, cotransfection of TH with AADC genes was readily accomplished by this procedure and resulted in a greater and longer-lasting improvement of apomorphine-induced rotational behavior than was achieved by transfection of TH gene alone. We suggest that this approach is a controllable and manageable alternative to other methods of gene therapy for the treatment of PD.

Animals↗
PubMed1992

Effect of a tyrosine kinase inhibitor, genistein, on the actions of prolactin in cultured mouse mammary tissues.

Genistein, an inhibitor of tyrosine kinase, was used to determine the possible role of tyrosine kinase in the prolactin (PRL) stimulation of milk product formation and ornithine decarboxylase (ODC) activation in cultured mouse mammary gland tissue. Genistein (10-200 microM) inhibited in a dose-response fashion the PRL stimulation of casein, lipid and lactose synthesis as well as ODC activation. Genistein, however, did not inhibit the phospholipase C, phorbol myristate acetate or cAMP effects on ODC activation. These results suggest the possible involvement of tyrosine kinase in the mechanism by which PRL expresses its effects in mammary gland tissues.

Animals↗
PubMed1992

Production of specific antibody against L-dopa and its ultrastructural localization of immunoreactivity in the house-shrew (Suncus murinus) lateral habenular nucleus.

An antiserum was raised against L-DOPA bound to bovine serum albumin, purified by affinity chromatography, and its specificities were verified by immunoblotting and enzyme-linked immunosorbent assays. The antiserum did not cross-react with dopamine (DA), tyrosine, tyramine, octopamine, norepinephrine or epinephrine. Immunocytochemical studies using the PAP method revealed that tyrosine hydroxylase- and L-DOPA positive but aromatic L-amino acid decarboxylase- and DA-negative neurons were present in the lateral habenular nucleus of the house-shrew (Suncus murinus) brain. Ultrastructurally L-DOPA immunoreactive products were localized in the cytoplasmic matrix and terminals with vesicles.

Animals↗
PubMed1982

Delays in growth and biochemical development of rat brain caused by maternal methadone administration: are the alterations in synaptogenesis and cellular maturation independent of reduced maternal food intake?

Food consumption of control pregnant and nursing rats was matched to that of methadone-treated dams and the patterns of growth and of biochemical development of the brain in the offspring were compared, using tyrosine hydroxylase activity as a marker for synaptogenesis of catecholamine neurons and the developmental pattern of ornithine decarboxylase activity as an index of delay of cellular maturation. Although body growth was slowed significantly, the degree of deficit was attenuated compared to previously reported experiments with non-pair-fed controls. Reduced brain weight and slowing of synaptogenesis also were evident in the methadone-exposed pups, and in this case, the effect was not attenuated with the use of pair-fed controls. Reduced brain weight and slowing of synaptogenesis also were evident in the methadone-exposed pups, and in this case, the effect was not attenuated with the use of pair-fed controls. Delays in the normal maturational decline of brain ornithine decarboxylase activity were prominent in the methadone group compared to offspring of pair-fed controls, just as reported previously in comparisons using non-pair-fed dams. These results indicate the part of the general growth deficit seen in perinatally-addicted pups is related to maternal undernutrition, but that delays in central synaptogenesis or in the pattern of biochemical maturation of the brain are relatively independent of the nutritional deficit.

Aging↗
PubMed1978

Effects of LSD and BOL on the catecholamine synthesis and turnover in various brain regions.

In the rat, lysergic acid diethylamide (LSD) 0.5 mg/kg and 2-bromo lysergic acid diethylamide (BOL) 0.5 mg/kg increased the rate of the striatal in vivo tyrosine hydroxylation as measured by the DOPA accumulation after decarboxylase inhibition. Neither LSD nor BOL significantly changed the DOPA accumulation in the olfactory tubercle, a dopamine-rich part of the limbic system. LSD but not BOL increased the DOPA accumulation in the cerebral cortex and in the brain stem. LSD and BOL appeared not to alter the rate of alpha-MT-induced disappearance of DA or of NA in the whole brain, nor did they change the rate of the alpha-MT-induced disappearance of DA in the striatum. It is suggested that in the striatum LSD and BOL block autoreceptorss (presynaptic receptors) regulating the tyrosine hydroxylation. These receptors may be DA receptor, but may also be 5-HT- or LSD-sensitive receptors. The regional differences observed between LSD and BOL suggest that LSD in the cerebral cortex and in the brain stem increases the DOPA accumulation by mechanism other than that functioning in the striatum. One possible explanation is that LSD and BOL may differ in their effects on 5-hydroxytryptaminergic systems in the cerebral cortex and in the brain stem.

Animals↗