stefano tacconi - Academia.edu (original) (raw)
Papers by stefano tacconi
The normal gut microbiota has several important functions in host physiology and metabolism, and ... more The normal gut microbiota has several important functions in host physiology and metabolism, and plays a key role in health and disease. Bifidobacteria, which are indigenous components of gastrointestinal microbiota, may play an important role in maintaining the well-being of the host although its precise function is very difficult to study. Its physiological and biochemical activities are controlled by many factors, particularly diet and environment. Adherence and colonization capacity are considered as contributing factors for immune modulation, pathogen exclusion, and enhanced contact with the mucosa. In this way, bifidobacteria would fortify the microbiota that forms an integral part of the mucosal barrier and colonization resistance against pathogens. Bifidobacteria are not only subjected to stressful conditions in industrial processes, but also in nature, where the ability to respond quickly to stress is essential for survival. Bifidobacteria, like other microorganisms, have e...
Bioorganic & medicinal chemistry letters, Jun 5, 2018
Hypothalamic CAMKK2 represents a potential mechanism for chemically affecting satiety and promoti... more Hypothalamic CAMKK2 represents a potential mechanism for chemically affecting satiety and promoting weight loss in clinically obese patients. Single-digit nanomolar inhibitors of CAMKK2 were identified in three related ATP-competitive series. Limited optimization of kinase selectivity, solubility, and pharmacokinetic properties were undertaken on all three series, as SAR was often transferrable. Ultimately, a 2,4-diaryl 7-azaindole was optimized to afford a tool molecule that potently inhibits AMPK phosphorylation in a hypothalamus-derived cell line, is orally bioavailable, and crosses the blood-brain barrier. When dosed orally in rodents, compound 4 t limited ghrelin-induced food intake.
Current Opinion in Pharmacology, 2017
Receptor distribution studies have played a key role in the characterization of receptor systems ... more Receptor distribution studies have played a key role in the characterization of receptor systems (e.g. GABA, NMDA (GluNRs), and Neurokinin 1) and in generating hypotheses to exploit these systems as potential therapeutic targets. Distribution studies can provide important information on the potential role of candidate receptors in normal physiology/disease and alert for possible adverse effects of targeting the receptors. Moreover, they can provide valuable information relating to quantitative target engagement (e.g. % receptor occupancy) to drive mechanistic pharmacokinetic/pharmacodynamic (PK/PD) hypotheses for compounds in the Drug Discovery process. Finally, receptor distribution and quantitative target engagement studies can be used to validate truly translational technologies such as PET ligands and pharmacoEEG paradigms to facilitate bridging of the preclinical/clinical interface and thus increase probability of success.
Comparative Biochemistry and Physiology Part C: Comparative Pharmacology, 1987
Goldfish injected with cadmium chloride synthesized metallothionein. Ten days after the first inj... more Goldfish injected with cadmium chloride synthesized metallothionein. Ten days after the first injection, cadmium reached a maximum in the metallothionein peak (2 micrograms/ml) obtained after gel filtration of liver cytosol. Pyruvate kinase activity was inhibited from the beginning of the experiment; after the fourth day, the enzyme activity again started to increase but did not reach the control level. Alkaline phosphatase and fructose biphosphatase did not show any apparent inhibition. From the results here reported, a detoxifying role of metallothionein could be suggested.
International journal of systematic and evolutionary microbiology, 2014
Six Gram-positive-staining, microaerophilic, non-spore-forming, fructose-6-phosphate phosphoketol... more Six Gram-positive-staining, microaerophilic, non-spore-forming, fructose-6-phosphate phosphoketolase-positive bacterial strains with a peculiar morphology were isolated from faecal samples of baby common marmosets (Callithrix jacchus). Cells of these strains showed a morphology not reported previously for a bifidobacterial species, which resembled a coiled snake, always coiled or ring shaped or forming a 'Y' shape. Strains MRM 3/1(T) and MRM 4/2 were chosen as representative strains and characterized further. The bacteria utilized a wide range of carbohydrates and produced urease. Glucose was fermented to acetate and lactate. Strain MRM 3/1(T) showed a peptidoglycan type unique among members of the genus Bifidobacterium. The DNA base composition was 64.7 mol% G+C. Almost-complete 16S rRNA, hsp60, clpC and rpoB gene sequences were obtained and phylogenetic relationships were determined. Comparative analysis of 16S rRNA gene sequences showed that strains MRM 3/1(T) and MRM 4/2...
European Journal of Pharmacology, 1990
Annals of Microbiology, 2012
Bifidobacteria are indigenous components of human and animal gastrointestinal microbiota, and the... more Bifidobacteria are indigenous components of human and animal gastrointestinal microbiota, and their health-promoting benefits have long been recognized. Of the 36 currently described species of the Bifidobacterium genus, 8 contain plasmids, most of which are cryptic. It is possible that plasmid presence is related very closely to environmental change, so in conditions of stress this presence could be specifically controlled. For plasmid-positive Bifidobacterium pseudolongum subsp. globosum RU809/1, the influence of the type and concentration of the carbohydrate source is evident in the dramatic pVS809 curing effect when growth is conducted in the presence of 0.15% (w/v) glucose, lactose, maltose, melibiose, raffinose or starch. The effect is linked to carbohydrate starvation, not to carbohydrate abundance, and is independent of biomass growth. Plasmid curing was achieved after one or two consecutive transfers, also in cells grown on medium containing 0.15% arabinose, fructose, galactose and sucrose, but not mannose, ribose or xylose. Knowing plasmid behavior in stressful conditions, like carbon source availability, has allowed an early insight into carbohydrate starvation as a curing agent for bifidobacteria. Furthermore, knowledge of plasmid behavior in stressful conditions could be important not only in genetics and ecology but also in food-grade and pharmaceutical applications for the development of cloning and expression vector systems for bifidobacteria.
Annals of Microbiology, 2012
Bifidobacteria are indigenous components of human and animal gastrointestinal microbiota, and the... more Bifidobacteria are indigenous components of human and animal gastrointestinal microbiota, and their health-promoting benefits have long been recognized. Of the 36 currently described species of the Bifidobacterium genus, 8 contain plasmids, most of which are cryptic. It is possible that plasmid presence is related very closely to environmental change, so in conditions of stress this presence could be specifically controlled. For plasmid-positive Bifidobacterium pseudolongum subsp. globosum RU809/1, the influence of the type and concentration of the carbohydrate source is evident in the dramatic pVS809 curing effect when growth is conducted in the presence of 0.15% (w/v) glucose, lactose, maltose, melibiose, raffinose or starch. The effect is linked to carbohydrate starvation, not to carbohydrate abundance, and is independent of biomass growth. Plasmid curing was achieved after one or two consecutive transfers, also in cells grown on medium containing 0.15% arabinose, fructose, galactose and sucrose, but not mannose, ribose or xylose. Knowing plasmid behavior in stressful conditions, like carbon source availability, has allowed an early insight into carbohydrate starvation as a curing agent for bifidobacteria. Furthermore, knowledge of plasmid behavior in stressful conditions could be important not only in genetics and ecology but also in food-grade and pharmaceutical applications for the development of cloning and expression vector systems for bifidobacteria.
Comparative Biochemistry and Physiology Part B: Biochemistry and Molecular Biology, 1989
1. In the posterior adductor muscle of Scapharca inaequivalvis both aspartate and glycogen were s... more 1. In the posterior adductor muscle of Scapharca inaequivalvis both aspartate and glycogen were substrates for anaerobic metabolism. ATP and arginine phosphate only contributed to a small extent. Alanine and succinate were major end products, whereas opines were minor end products. Lactate production was not observed.
Molecular Brain Research, 1998
MAPK pathways transduce a broad variety of extracellular signals into cellular responses. Despite... more MAPK pathways transduce a broad variety of extracellular signals into cellular responses. Despite their pleiotropic effects and their ubiquitous distribution, surprisingly little is known about their involvement in the communication network of nerve cells. As a first step to elucidate the role of MAPK pathways in neuronal signalling, we studied the distribution of SAPK arJNK2, SAPK brJNK3, and SAPK grJNK1, three isoforms of SAPKrJNK, a stress-activated MAPK subfamily. We compared the mRNA localisation of the three main isoforms in the adult and developing rat brain using in situ hybridisation. In the adult brain, SAPK a and b were widely but heterogeneously distributed, reproducing the pattern of a probe that does not discriminate the isoforms. Differently, high labelling for the SAPK g probe was exclusively localised in the endopiriform nucleus and medial habenula. Intermediate staining was detected in the hippocampus. During post-natal development, SAPK b showed the same localisation as in the adult. Nevertheless, the semi-quantitative analysis of optical densities showed significantly different mRNA levels. In the adult, SAPK g signal was weak, whereas in newborn rats the labelling was intense and widely distributed. SAPK g mRNA levels decreased during development, to reach the low signals detected in the adult. These results suggest that in the central nervous system SAPK-type MAP kinases perform significant physiological functions which are particularly relevant during post-natal development. The distinct distribution patterns of SAPK isoforms in the adult rat brain support the hypothesis that separate functions are performed by the products of the three SAPK genes. q 1998 Elsevier Science B.V. All rights reserved.
Neuroscience, 2001
AbstractÐSmall conductance calcium-activated potassium channels are voltage independent potassium... more AbstractÐSmall conductance calcium-activated potassium channels are voltage independent potassium channels which modulate the ®ring patterns of neurons by activating the slow component of the afterhyperpolarization. The genes encoding a family of small conductance calcium-activated potassium channels have been cloned and up to now three known members have been described and named small conductance calcium-activated potassium channel type 1, small conductance calciumactivated potassium channel type 2 and small conductance calcium-activated potassium channel type 3; the distribution of their messenger RNA in the rat CNS has already been performed but only in a limited detail.
Neuroscience, 1997
Stress-activated protein kinase/extracellular signal-regulated protein kinase-1/c-Jun NH2-termina... more Stress-activated protein kinase/extracellular signal-regulated protein kinase-1/c-Jun NH2-terminal kinase kinase is a dual-specificity kinase which phosphorylates and activates stress-activated protein kinase/c-Jun NH2-terminal kinase, a recently discovered mitogen-activated protein kinase that is stimulated by stressful stimuli and that regulates cellular transcriptional activity. The distribution of the messenger RNA encoding for stress-activated protein kinase/extracellular signal-regulated protein kinase-1 was evaluated in the adult and developing rat central nervous system. In situ hybridization with a 35S-labelled 45mer oligodeoxynucleotide probe was used to map the distribution of the stress-activated protein kinase/extracellular signal-regulated protein kinase-1 messenger RNA in postnatal day 1, 3, 6, 9, 12, 15, 18, 21 and adult rat brains. Specific labelling was generally associated with neuronal profiles. In the adult central nervous system, high hybridization signals were observed in the hippocampus, the granular layer of the cerebellum, the medial habenula, the anterodorsal thalamic nucleus, the red nucleus, the pontine nuclei, the facial nucleus, the motor and mesencephalic nuclei of the trigeminal nerve, the hypoglossal nucleus, the vestibular nucleus and the nucleus ambiguus. Intermediate levels were present in diencephalic and mesencephalic regions and in the neocortex, while basal ganglia displayed a low hybridization signal. In the developing brain, the heterogeneous distribution of the hybridization signal observed in the adult brain was already present, but in the hippocampus and basal ganglia the stress-activated protein kinase/extracellular signal-regulated protein kinase-1 messenger RNA levels were significantly higher at postnatal day 3 and during the second postnatal week than in the adult. The results show that stress-activated protein kinase/extracellular signal-regulated protein kinase-1 is widely expressed in the rat central nervous system and co-localizes with its substrate stress-activated protein kinase. The observed changes in stress-activated protein kinase/extracellular signal-regulated protein kinase-1 messenger RNA levels during postnatal development suggest a role for this protein in the maturation of brain circuits.
Neuroscience, 1995
Mitogen-activated protein kinases are important mediators of signal transduction from the cell su... more Mitogen-activated protein kinases are important mediators of signal transduction from the cell surface to the nucleus and their activation has been implicated in a wide array of physiological processes. The extracellular-signal-regulated kinases are the archetypal and best studied members of the mitogen activated protein kinases. Recently, additional subgroups of mitogen activated protein kinases have been identified which exhibit distinct regulatory elements, substrate specificity and respond to diverse extracellular stimuli. Among these newly identified protein kinases are the rat stress-activated protein kinases. Despite a rapidly expanding literature on the biochemical properties of stress-activated protein kinases no anatomical data are yet available. In the present study, we have investigated the regional distribution of messenger RNA transcripts for stress-activated protein kinases in the adult rat central nervous system and compared this distribution to that observed for extracellular-signal-regulated kinases. Intense labelling for stress-activated protein kinases could be detected in discrete brain areas with high levels in hippocampus, neocortex and some nuclei of the brain stem. The apparent hybridization signal appeared to be selectively neuronal.
Nature Neuroscience, 2001
Both ionotropic and metabotropic glutamate receptors (mGluRs) are involved in the behavioral effe... more Both ionotropic and metabotropic glutamate receptors (mGluRs) are involved in the behavioral effects of pyschostimulants; however, the specific contributions of individual mGluR subtypes remain unknown. Here we show that mice lacking the mGluR5 gene do not self-administer cocaine, and show no increased locomotor activity following cocaine treatment, despite showing cocaine-induced increases in nucleus accumbens (NAcc) dopamine (DA) levels similar to wild-type (WT) mice. These results demonstrate a significant contribution of mGlu5 receptors to the behavioral effects of cocaine, and suggest that they may be involved in cocaine addiction.
Pharmacological Research, 1990
The normal gut microbiota has several important functions in host physiology and metabolism, and ... more The normal gut microbiota has several important functions in host physiology and metabolism, and plays a key role in health and disease. Bifidobacteria, which are indigenous components of gastrointestinal microbiota, may play an important role in maintaining the well-being of the host although its precise function is very difficult to study. Its physiological and biochemical activities are controlled by many factors, particularly diet and environment. Adherence and colonization capacity are considered as contributing factors for immune modulation, pathogen exclusion, and enhanced contact with the mucosa. In this way, bifidobacteria would fortify the microbiota that forms an integral part of the mucosal barrier and colonization resistance against pathogens. Bifidobacteria are not only subjected to stressful conditions in industrial processes, but also in nature, where the ability to respond quickly to stress is essential for survival. Bifidobacteria, like other microorganisms, have e...
Bioorganic & medicinal chemistry letters, Jun 5, 2018
Hypothalamic CAMKK2 represents a potential mechanism for chemically affecting satiety and promoti... more Hypothalamic CAMKK2 represents a potential mechanism for chemically affecting satiety and promoting weight loss in clinically obese patients. Single-digit nanomolar inhibitors of CAMKK2 were identified in three related ATP-competitive series. Limited optimization of kinase selectivity, solubility, and pharmacokinetic properties were undertaken on all three series, as SAR was often transferrable. Ultimately, a 2,4-diaryl 7-azaindole was optimized to afford a tool molecule that potently inhibits AMPK phosphorylation in a hypothalamus-derived cell line, is orally bioavailable, and crosses the blood-brain barrier. When dosed orally in rodents, compound 4 t limited ghrelin-induced food intake.
Current Opinion in Pharmacology, 2017
Receptor distribution studies have played a key role in the characterization of receptor systems ... more Receptor distribution studies have played a key role in the characterization of receptor systems (e.g. GABA, NMDA (GluNRs), and Neurokinin 1) and in generating hypotheses to exploit these systems as potential therapeutic targets. Distribution studies can provide important information on the potential role of candidate receptors in normal physiology/disease and alert for possible adverse effects of targeting the receptors. Moreover, they can provide valuable information relating to quantitative target engagement (e.g. % receptor occupancy) to drive mechanistic pharmacokinetic/pharmacodynamic (PK/PD) hypotheses for compounds in the Drug Discovery process. Finally, receptor distribution and quantitative target engagement studies can be used to validate truly translational technologies such as PET ligands and pharmacoEEG paradigms to facilitate bridging of the preclinical/clinical interface and thus increase probability of success.
Comparative Biochemistry and Physiology Part C: Comparative Pharmacology, 1987
Goldfish injected with cadmium chloride synthesized metallothionein. Ten days after the first inj... more Goldfish injected with cadmium chloride synthesized metallothionein. Ten days after the first injection, cadmium reached a maximum in the metallothionein peak (2 micrograms/ml) obtained after gel filtration of liver cytosol. Pyruvate kinase activity was inhibited from the beginning of the experiment; after the fourth day, the enzyme activity again started to increase but did not reach the control level. Alkaline phosphatase and fructose biphosphatase did not show any apparent inhibition. From the results here reported, a detoxifying role of metallothionein could be suggested.
International journal of systematic and evolutionary microbiology, 2014
Six Gram-positive-staining, microaerophilic, non-spore-forming, fructose-6-phosphate phosphoketol... more Six Gram-positive-staining, microaerophilic, non-spore-forming, fructose-6-phosphate phosphoketolase-positive bacterial strains with a peculiar morphology were isolated from faecal samples of baby common marmosets (Callithrix jacchus). Cells of these strains showed a morphology not reported previously for a bifidobacterial species, which resembled a coiled snake, always coiled or ring shaped or forming a 'Y' shape. Strains MRM 3/1(T) and MRM 4/2 were chosen as representative strains and characterized further. The bacteria utilized a wide range of carbohydrates and produced urease. Glucose was fermented to acetate and lactate. Strain MRM 3/1(T) showed a peptidoglycan type unique among members of the genus Bifidobacterium. The DNA base composition was 64.7 mol% G+C. Almost-complete 16S rRNA, hsp60, clpC and rpoB gene sequences were obtained and phylogenetic relationships were determined. Comparative analysis of 16S rRNA gene sequences showed that strains MRM 3/1(T) and MRM 4/2...
European Journal of Pharmacology, 1990
Annals of Microbiology, 2012
Bifidobacteria are indigenous components of human and animal gastrointestinal microbiota, and the... more Bifidobacteria are indigenous components of human and animal gastrointestinal microbiota, and their health-promoting benefits have long been recognized. Of the 36 currently described species of the Bifidobacterium genus, 8 contain plasmids, most of which are cryptic. It is possible that plasmid presence is related very closely to environmental change, so in conditions of stress this presence could be specifically controlled. For plasmid-positive Bifidobacterium pseudolongum subsp. globosum RU809/1, the influence of the type and concentration of the carbohydrate source is evident in the dramatic pVS809 curing effect when growth is conducted in the presence of 0.15% (w/v) glucose, lactose, maltose, melibiose, raffinose or starch. The effect is linked to carbohydrate starvation, not to carbohydrate abundance, and is independent of biomass growth. Plasmid curing was achieved after one or two consecutive transfers, also in cells grown on medium containing 0.15% arabinose, fructose, galactose and sucrose, but not mannose, ribose or xylose. Knowing plasmid behavior in stressful conditions, like carbon source availability, has allowed an early insight into carbohydrate starvation as a curing agent for bifidobacteria. Furthermore, knowledge of plasmid behavior in stressful conditions could be important not only in genetics and ecology but also in food-grade and pharmaceutical applications for the development of cloning and expression vector systems for bifidobacteria.
Annals of Microbiology, 2012
Bifidobacteria are indigenous components of human and animal gastrointestinal microbiota, and the... more Bifidobacteria are indigenous components of human and animal gastrointestinal microbiota, and their health-promoting benefits have long been recognized. Of the 36 currently described species of the Bifidobacterium genus, 8 contain plasmids, most of which are cryptic. It is possible that plasmid presence is related very closely to environmental change, so in conditions of stress this presence could be specifically controlled. For plasmid-positive Bifidobacterium pseudolongum subsp. globosum RU809/1, the influence of the type and concentration of the carbohydrate source is evident in the dramatic pVS809 curing effect when growth is conducted in the presence of 0.15% (w/v) glucose, lactose, maltose, melibiose, raffinose or starch. The effect is linked to carbohydrate starvation, not to carbohydrate abundance, and is independent of biomass growth. Plasmid curing was achieved after one or two consecutive transfers, also in cells grown on medium containing 0.15% arabinose, fructose, galactose and sucrose, but not mannose, ribose or xylose. Knowing plasmid behavior in stressful conditions, like carbon source availability, has allowed an early insight into carbohydrate starvation as a curing agent for bifidobacteria. Furthermore, knowledge of plasmid behavior in stressful conditions could be important not only in genetics and ecology but also in food-grade and pharmaceutical applications for the development of cloning and expression vector systems for bifidobacteria.
Comparative Biochemistry and Physiology Part B: Biochemistry and Molecular Biology, 1989
1. In the posterior adductor muscle of Scapharca inaequivalvis both aspartate and glycogen were s... more 1. In the posterior adductor muscle of Scapharca inaequivalvis both aspartate and glycogen were substrates for anaerobic metabolism. ATP and arginine phosphate only contributed to a small extent. Alanine and succinate were major end products, whereas opines were minor end products. Lactate production was not observed.
Molecular Brain Research, 1998
MAPK pathways transduce a broad variety of extracellular signals into cellular responses. Despite... more MAPK pathways transduce a broad variety of extracellular signals into cellular responses. Despite their pleiotropic effects and their ubiquitous distribution, surprisingly little is known about their involvement in the communication network of nerve cells. As a first step to elucidate the role of MAPK pathways in neuronal signalling, we studied the distribution of SAPK arJNK2, SAPK brJNK3, and SAPK grJNK1, three isoforms of SAPKrJNK, a stress-activated MAPK subfamily. We compared the mRNA localisation of the three main isoforms in the adult and developing rat brain using in situ hybridisation. In the adult brain, SAPK a and b were widely but heterogeneously distributed, reproducing the pattern of a probe that does not discriminate the isoforms. Differently, high labelling for the SAPK g probe was exclusively localised in the endopiriform nucleus and medial habenula. Intermediate staining was detected in the hippocampus. During post-natal development, SAPK b showed the same localisation as in the adult. Nevertheless, the semi-quantitative analysis of optical densities showed significantly different mRNA levels. In the adult, SAPK g signal was weak, whereas in newborn rats the labelling was intense and widely distributed. SAPK g mRNA levels decreased during development, to reach the low signals detected in the adult. These results suggest that in the central nervous system SAPK-type MAP kinases perform significant physiological functions which are particularly relevant during post-natal development. The distinct distribution patterns of SAPK isoforms in the adult rat brain support the hypothesis that separate functions are performed by the products of the three SAPK genes. q 1998 Elsevier Science B.V. All rights reserved.
Neuroscience, 2001
AbstractÐSmall conductance calcium-activated potassium channels are voltage independent potassium... more AbstractÐSmall conductance calcium-activated potassium channels are voltage independent potassium channels which modulate the ®ring patterns of neurons by activating the slow component of the afterhyperpolarization. The genes encoding a family of small conductance calcium-activated potassium channels have been cloned and up to now three known members have been described and named small conductance calcium-activated potassium channel type 1, small conductance calciumactivated potassium channel type 2 and small conductance calcium-activated potassium channel type 3; the distribution of their messenger RNA in the rat CNS has already been performed but only in a limited detail.
Neuroscience, 1997
Stress-activated protein kinase/extracellular signal-regulated protein kinase-1/c-Jun NH2-termina... more Stress-activated protein kinase/extracellular signal-regulated protein kinase-1/c-Jun NH2-terminal kinase kinase is a dual-specificity kinase which phosphorylates and activates stress-activated protein kinase/c-Jun NH2-terminal kinase, a recently discovered mitogen-activated protein kinase that is stimulated by stressful stimuli and that regulates cellular transcriptional activity. The distribution of the messenger RNA encoding for stress-activated protein kinase/extracellular signal-regulated protein kinase-1 was evaluated in the adult and developing rat central nervous system. In situ hybridization with a 35S-labelled 45mer oligodeoxynucleotide probe was used to map the distribution of the stress-activated protein kinase/extracellular signal-regulated protein kinase-1 messenger RNA in postnatal day 1, 3, 6, 9, 12, 15, 18, 21 and adult rat brains. Specific labelling was generally associated with neuronal profiles. In the adult central nervous system, high hybridization signals were observed in the hippocampus, the granular layer of the cerebellum, the medial habenula, the anterodorsal thalamic nucleus, the red nucleus, the pontine nuclei, the facial nucleus, the motor and mesencephalic nuclei of the trigeminal nerve, the hypoglossal nucleus, the vestibular nucleus and the nucleus ambiguus. Intermediate levels were present in diencephalic and mesencephalic regions and in the neocortex, while basal ganglia displayed a low hybridization signal. In the developing brain, the heterogeneous distribution of the hybridization signal observed in the adult brain was already present, but in the hippocampus and basal ganglia the stress-activated protein kinase/extracellular signal-regulated protein kinase-1 messenger RNA levels were significantly higher at postnatal day 3 and during the second postnatal week than in the adult. The results show that stress-activated protein kinase/extracellular signal-regulated protein kinase-1 is widely expressed in the rat central nervous system and co-localizes with its substrate stress-activated protein kinase. The observed changes in stress-activated protein kinase/extracellular signal-regulated protein kinase-1 messenger RNA levels during postnatal development suggest a role for this protein in the maturation of brain circuits.
Neuroscience, 1995
Mitogen-activated protein kinases are important mediators of signal transduction from the cell su... more Mitogen-activated protein kinases are important mediators of signal transduction from the cell surface to the nucleus and their activation has been implicated in a wide array of physiological processes. The extracellular-signal-regulated kinases are the archetypal and best studied members of the mitogen activated protein kinases. Recently, additional subgroups of mitogen activated protein kinases have been identified which exhibit distinct regulatory elements, substrate specificity and respond to diverse extracellular stimuli. Among these newly identified protein kinases are the rat stress-activated protein kinases. Despite a rapidly expanding literature on the biochemical properties of stress-activated protein kinases no anatomical data are yet available. In the present study, we have investigated the regional distribution of messenger RNA transcripts for stress-activated protein kinases in the adult rat central nervous system and compared this distribution to that observed for extracellular-signal-regulated kinases. Intense labelling for stress-activated protein kinases could be detected in discrete brain areas with high levels in hippocampus, neocortex and some nuclei of the brain stem. The apparent hybridization signal appeared to be selectively neuronal.
Nature Neuroscience, 2001
Both ionotropic and metabotropic glutamate receptors (mGluRs) are involved in the behavioral effe... more Both ionotropic and metabotropic glutamate receptors (mGluRs) are involved in the behavioral effects of pyschostimulants; however, the specific contributions of individual mGluR subtypes remain unknown. Here we show that mice lacking the mGluR5 gene do not self-administer cocaine, and show no increased locomotor activity following cocaine treatment, despite showing cocaine-induced increases in nucleus accumbens (NAcc) dopamine (DA) levels similar to wild-type (WT) mice. These results demonstrate a significant contribution of mGlu5 receptors to the behavioral effects of cocaine, and suggest that they may be involved in cocaine addiction.
Pharmacological Research, 1990