Juan Hidalgo - Academia.edu (original) (raw)

Papers by Juan Hidalgo

Research paper thumbnail of Metallothionein expression and oxidative stress in the brain

Methods in Enzymology, Feb 1, 2002

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Research paper thumbnail of Sex and restraint stress differences in rat metallothionein and Zn levels

Revista Espanola De Fisiologia, 1988

Sex differences in serum and liver metallothionein (MT) levels were studied in adult male and fem... more Sex differences in serum and liver metallothionein (MT) levels were studied in adult male and female rats. Whereas it was found that female rats had higher hepatic MT levels than male rats in basal, unstressed conditions, no significant differences were found in serum MT levels. Restraint stress increased both serum and liver MT in both sexes. The increase in serum MT was greater in male than in female rats, whereas no significant differences between sexes were found in liver MT content after restraint stress. It is suggested that MT regulation might be sex-dependent and that MT might play some extrahepatic function during stress.

Research paper thumbnail of Short-term cadnium effects on gill tissue metabolism

Marine Pollution Bulletin, 1984

Research paper thumbnail of Vortical hot towers, their aggregate effects and their resolution dependence in the formation of Hurricane Diana (1984)

Recent authors have hypothesized that small-scale deep convective towers possessing intense value... more Recent authors have hypothesized that small-scale deep convective towers possessing intense values of cyclonic vertical vorticity in their cores (vortical hot towers) play a critical role in tropical cyclogenesis via a two stage process: (1) preconditioning the local environment by creating small-scale potential vorticity anomalies and humidifying the lower to middle troposphere, and (2) merger, axisymmetrization and collection of these potential vorticity anomalies to generate the larger scale vortex. In this study we further investigate the role played by vortical hot towers in the upscale growth process. We simulate the evolution of Hurricane Diana in a full-physics numerical model with 1km grid spacing and compare our results to previous, coarser resolution simulations. We employ traditional weather analysis techniques and new innovative means of displaying large and complex datasets to investigate the interaction between the cloud scale features and the larger system scale environment. The results are compared to prior studies to assess if simulated vortical hot tower dynamics exhibit a significant dependence on model resolution. We find the basic physics of the vortical hot tower pathway is largely unchanged as grid-spacing decreases from 3km to 1km for simulations of Hurricane Diana. The differences between our high resolution simulation and coarser resolution simulations are mainly associated with fine scale variability. Our 1km simulation represents nearly an order of magnitude more convective towers with smaller spatial scales than what was observed in previous simulations. We find maximum updraft velocities in our 1km simulation typically between 15ms-1 and 20ms-1 with instantaneous maximum values as high as 35ms-1, though these values typically decrease during the simulation. We also find that, while the cores in the vortical hot towers are significantly moistened by the vertical transport of moisture in the updraft, the larger-scale environment actually dries significantly due to horizontal advection. Lastly, we examine a series of vortex merger events and find that merger activity is a ubiquitous and important aspect of the genesis of Hurricane Diana. Our results broadly confirm previous work using coarser numerical resolution and provide new insights into the hypothesized upscale growth process in incipient hurricanes.

Research paper thumbnail of Metallothionein-I overexpression decreases brain pathology in transgenic mice with astrocyte-targeted expression of interleukin-6

Journal of Neuropathology and Experimental Neurology, Apr 1, 2003

Transgenic expression of interleukin-6 (IL-6) in the CNS under the control of the glial fibrillar... more Transgenic expression of interleukin-6 (IL-6) in the CNS under the control of the glial fibrillary acidic protein (GFAP) gene promoter (GFAP-IL6 mice) causes significant damage and alters the expression of many genes, including a dramatic upregulation of metallothionein-I (MT-I). The findings in this report support the idea that the upregulation of MT-I observed in GFAP-IL6 mice is an important mechanism for coping with brain damage. Thus, GFAP-IL6 mice that were crossed with TgMTI transgenic mice (GFAP-IL6xTgMTI) and overexpressed MT-I in the brain showed a decreased upregulation of cytokines such as IL-6 and a diminished recruitment and activation of macrophages and T cells throughout the CNS but mainly in the cerebellum. The GFAP-IL6 mice showed clear evidence of increased oxidative stress, which was significantly decreased by MT-I overexpression. Interestingly, MT-I overexpression increased angiogenesis in GFAP-IL6 mice but not in control littermates. Overall, the results strongly suggest that MT-I+II proteins are valuable factors that protect against cytokine-induced CNS injury.

Research paper thumbnail of Vitamin E-Supplemented Diets Reduce Lipid Peroxidation but Do Not Alter Either Pituitary-Adrenal, Glucose, and Lactate Responses to Immobilization Stress or Gastric Ulceration

Research paper thumbnail of Site-specific targeting of autoimmunity in mice induced by the localized production of IL-6

The Faseb Journal, Mar 1, 2008

Research paper thumbnail of Transgenic mice with astrocyte-targeted production of interleulcin-6 are resistant to high-fat diet-induced increases in body weight and body fat

Brain Behavior and Immunity, 2010

Research paper thumbnail of Non-Gaussian corrections to the probability distribution of the curvature perturbation from inflation

Jcap, 2006

We show how to obtain the probability density function for the amplitude of the curvature perturb... more We show how to obtain the probability density function for the amplitude of the curvature perturbation, \mathcal {R} , produced during an epoch of slow-roll, single-field inflation, working directly from n-point correlation functions of \mathcal {R} . These n-point functions are the usual output of quantum field theory calculations, and as a result we bypass approximate statistical arguments based on the central limit theorem. Our method can be extended to deal with arbitrary forms of non-Gaussianity, appearing at any order in the n-point hierarchy. We compute the probability density for the total smoothed perturbation within a Hubble volume, epsi, and for the spectrum of epsi. When only the two-point function is retained, exact Gaussian statistics are recovered. For when the three-point function is taken into account, we compute explicitly the leading slow-roll correction to the Gaussian result.

Research paper thumbnail of Distribution of metallothionein I + II and vesicular zinc in the developing central nervous system: Correlative study in the rat

The Journal of Comparative Neurology, Sep 20, 1999

Because zinc (Zn) is a co-factor in enzymes and participates in neurotransmission, it is essentia... more Because zinc (Zn) is a co-factor in enzymes and participates in neurotransmission, it is essential for brain development. However, because excess Zn may cause neuronal injury, cerebral mechanisms for Zn regulation must operate. The metallothionein isoforms I and II (MT I + II) are putative candidates for chelating unbound Zn released from Zn-containing nerve terminals or transported into the brain. Whether vesicular Zn and MT I + II occur in identical regions of the developing brain is unknown. Accordingly, the developmental distribution of MT I + II and vesicular Zn was mapped. By using double-labeling fluorescence histochemistry, MT I + II immunoreactivity (ir) was attributed to astrocytes and cells of myelomonocytic lineage. The cells of the myelomonocytic lineage shared the morphology of monocytes and macrophages but not of microglia and occurred primarily around vessels and ventricles in the brainstem. By contrast, astrocytes were widespread throughout the developing brain. In embryonic and neonatal brain, MT I + IIir astrocytes were almost selectively observed in the septum and fascia dentate hilus (hi) of the hippocampus. With increasing postnatal age, they also occurred in hippocampal cortex, basal forebrain, neocortex, cerebellar cortex, and cranial nerve nuclei. MT I + II mRNAs were detected in regions of the brain that also displayed MT I + IIir, indicating transcriptional events. Vesicular Zn was recorded in neonatal brain solely in the dentate hi of the hippocampus. With increasing age, the amount of vesicular Zn increased in the hippocampus and other forebrain regions. The presence of MT I + II proteins in the developing brain was confirmed by radioimmunoassay. The regional distribution of astrocytic MT I + IIir and vesicular Zn suggests that MT I + II are implicated in Zn metabolism in the developing forebrain.

Research paper thumbnail of Astrocytic IL-6 Influences the Clinical Symptoms of EAE in Mice

Brain Sciences, 2016

Interleukin-6 (IL-6) is a multifunctional cytokine that not only plays major roles in the immune ... more Interleukin-6 (IL-6) is a multifunctional cytokine that not only plays major roles in the immune system, but also serves as a coordinator between the nervous and endocrine systems. IL-6 is produced in multiple cell types in the CNS, and in turn, many cells respond to it. It is therefore important to ascertain which cell type is the key responder to IL-6 during both physiological and pathological conditions. In order to test the role of astrocytic IL-6 in neuroinflammation, we studied an extensively-used animal model of multiple sclerosis, experimental autoimmune encephalomyelitis (EAE), in mice with an IL-6 deficiency in astrocytes (Ast-IL-6 KO). Results indicate that lack of astrocytic IL-6 did not cause major changes in EAE symptomatology. However, a delay in the onset of clinical signs was observed in Ast-IL-6 KO females, with fewer inflammatory infiltrates and decreased demyelination and some alterations in gliosis and vasogenesis, compared to floxed mice. These results suggest that astrocyte-secreted IL-6 has some roles in EAE pathogenesis, at least in females.

Research paper thumbnail of PGC-1 is not mandatory for exercise- and training-induced adaptive gene responses in mouse skeletal muscle

Amer J Physiol Endocrinol Met, 2007

Research paper thumbnail of Metallothionein Treatment Reduces Proinflammatory Cytokines IL-6 and TNF-α and Apoptotic Cell Death during Experimental Autoimmune Encephalomyelitis (EAE)

Experimental Neurology, Jul 31, 2001

Research paper thumbnail of Phosphodiesterase 5 inhibition at disease onset prevents experimental autoimmune encephalomyelitis progression through immunoregulatory and neuroprotective actions

Experimental Neurology, Nov 6, 2013

Research paper thumbnail of Metallothionein-mediated antioxidant defense system and its response to exercise training are impaired in human type 2 diabetes. Diabetes 2005;54:3089–3094

Research paper thumbnail of Expression of growth inhibitory factor (metallothionein-III) mRNA and protein following excitotoxic immature brain injury

Journal of Neuropathology and Experimental Neurology, May 1, 1999

The balance between trophic factors and inhibitory molecules is likely to determine the outcome o... more The balance between trophic factors and inhibitory molecules is likely to determine the outcome of neural tissue damage. The growth inhibitory factor (GIF), a member of the metallothionein family of proteins named metallothionein-III (MT-III), has been suggested to play an important role in tissue repair after adult brain injury. Because no information is available on this factor in relation to immature brain damage, we examined the chronological changes of GIF (MT-III) mRNA and protein following excitotoxic lesions to the postnatal day 9 brain using in situ hybridization and immunocytochemical techniques. We observed a significant decrease of neuronal GIF (MT-III) mRNA and protein levels between 4 and 24 hours postinjury and an increase in glial GIF (MT-III) levels. Double immunocytochemical techniques showed GIF (MT-III) and GFAP positive astrocytes from 2-4 hours postinjury. From 3 days postinjury strongly reactive astrocytes expressed strong levels of both GIF (MT-III) mRNA and protein, which were maintained in the glial scar formed at longer times. These results show the expression of an inhibitory molecule by postnatal reactive astrocytes. Glial GIF (MT-III) expression may play an important role in the tissue reconstruction after immature brain damage.

Research paper thumbnail of Hypoxic Preconditioning Induces Neuroprotective Stanniocalcin-1 in Brain via IL-6 Signaling

Research paper thumbnail of The pupal morphology of the Carabus (s. l.) (Coleoptera, Carabidae) of the southwestern Iberian peninsula

Animal Biodiversity and Conservation, 2002

Research paper thumbnail of Role of Glucocorticoids on Rat Brain Metallothionein-I and-III Response to Stress

The metallothionein (MT) gene family consists of four members (MT-I through -IV) that are tightly... more The metallothionein (MT) gene family consists of four members (MT-I through -IV) that are tightly regulated during development. Whereas MT-I and MT-II are widely expressed isoforms, MT-III has been found to be mainly expressed in the central nervous system in adult animals, and is the only isoform that inhibits survival and neurite formation of cortical neurons in vitro. A number of models of brain injury have been shown to affect MT-III mRNA levels, which has been suggested to be related to the putative neurotrophic role of this protein. However, a stress response will presumably be associated to the brain injury which could, in turn, drive MT-III regulation. In the present report the effect of a classical stress model, immobilization stress, on brain MT regulation has been studied in rats. MT-I+II protein levels were measured by radioimmunoassay in up to eight brain areas and, as expected, it was found that stress increased selectively MT-I+II levels. Adrenalectomy (ADX) had a general decreasing effect on basal MT-I+II levels; however, ADX blunted the MT-I+II response to stress in cerebellum and presumably in frontal cortex and medulla plus pons but not in the hypothalamus. MT-I mRNA measurements were in accordance with the MT-I+II protein levels in the brain areas studied. In contrast to MT-I mRNA, MT-III mRNA levels of brain cortex tended to decrease during stress, although this effect was not statistically significant. ADX also tended to decrease basal MT-III mRNA levels. Northern blot assays of pooled mRNAs suggested similar differential regulation of these two brain MT isoforms in the cerebellum. These results indicate that glucocorticoids mediate brain MT-I+II response to stress in some but not all brain areas, that a role of these hormones is likely also for MT-III, and that the regulation of MT isoforms differs substantially in the brain.

Research paper thumbnail of Interleukin-6 regulation of ΑΜP-activated protein kinase : Potential role in the systemic response to exercise and prevention of the metabolic syndrome

Research paper thumbnail of Metallothionein expression and oxidative stress in the brain

Methods in Enzymology, Feb 1, 2002

RefDoc Bienvenue - Welcome. Refdoc est un service / is powered by. ...

Research paper thumbnail of Sex and restraint stress differences in rat metallothionein and Zn levels

Revista Espanola De Fisiologia, 1988

Sex differences in serum and liver metallothionein (MT) levels were studied in adult male and fem... more Sex differences in serum and liver metallothionein (MT) levels were studied in adult male and female rats. Whereas it was found that female rats had higher hepatic MT levels than male rats in basal, unstressed conditions, no significant differences were found in serum MT levels. Restraint stress increased both serum and liver MT in both sexes. The increase in serum MT was greater in male than in female rats, whereas no significant differences between sexes were found in liver MT content after restraint stress. It is suggested that MT regulation might be sex-dependent and that MT might play some extrahepatic function during stress.

Research paper thumbnail of Short-term cadnium effects on gill tissue metabolism

Marine Pollution Bulletin, 1984

Research paper thumbnail of Vortical hot towers, their aggregate effects and their resolution dependence in the formation of Hurricane Diana (1984)

Recent authors have hypothesized that small-scale deep convective towers possessing intense value... more Recent authors have hypothesized that small-scale deep convective towers possessing intense values of cyclonic vertical vorticity in their cores (vortical hot towers) play a critical role in tropical cyclogenesis via a two stage process: (1) preconditioning the local environment by creating small-scale potential vorticity anomalies and humidifying the lower to middle troposphere, and (2) merger, axisymmetrization and collection of these potential vorticity anomalies to generate the larger scale vortex. In this study we further investigate the role played by vortical hot towers in the upscale growth process. We simulate the evolution of Hurricane Diana in a full-physics numerical model with 1km grid spacing and compare our results to previous, coarser resolution simulations. We employ traditional weather analysis techniques and new innovative means of displaying large and complex datasets to investigate the interaction between the cloud scale features and the larger system scale environment. The results are compared to prior studies to assess if simulated vortical hot tower dynamics exhibit a significant dependence on model resolution. We find the basic physics of the vortical hot tower pathway is largely unchanged as grid-spacing decreases from 3km to 1km for simulations of Hurricane Diana. The differences between our high resolution simulation and coarser resolution simulations are mainly associated with fine scale variability. Our 1km simulation represents nearly an order of magnitude more convective towers with smaller spatial scales than what was observed in previous simulations. We find maximum updraft velocities in our 1km simulation typically between 15ms-1 and 20ms-1 with instantaneous maximum values as high as 35ms-1, though these values typically decrease during the simulation. We also find that, while the cores in the vortical hot towers are significantly moistened by the vertical transport of moisture in the updraft, the larger-scale environment actually dries significantly due to horizontal advection. Lastly, we examine a series of vortex merger events and find that merger activity is a ubiquitous and important aspect of the genesis of Hurricane Diana. Our results broadly confirm previous work using coarser numerical resolution and provide new insights into the hypothesized upscale growth process in incipient hurricanes.

Research paper thumbnail of Metallothionein-I overexpression decreases brain pathology in transgenic mice with astrocyte-targeted expression of interleukin-6

Journal of Neuropathology and Experimental Neurology, Apr 1, 2003

Transgenic expression of interleukin-6 (IL-6) in the CNS under the control of the glial fibrillar... more Transgenic expression of interleukin-6 (IL-6) in the CNS under the control of the glial fibrillary acidic protein (GFAP) gene promoter (GFAP-IL6 mice) causes significant damage and alters the expression of many genes, including a dramatic upregulation of metallothionein-I (MT-I). The findings in this report support the idea that the upregulation of MT-I observed in GFAP-IL6 mice is an important mechanism for coping with brain damage. Thus, GFAP-IL6 mice that were crossed with TgMTI transgenic mice (GFAP-IL6xTgMTI) and overexpressed MT-I in the brain showed a decreased upregulation of cytokines such as IL-6 and a diminished recruitment and activation of macrophages and T cells throughout the CNS but mainly in the cerebellum. The GFAP-IL6 mice showed clear evidence of increased oxidative stress, which was significantly decreased by MT-I overexpression. Interestingly, MT-I overexpression increased angiogenesis in GFAP-IL6 mice but not in control littermates. Overall, the results strongly suggest that MT-I+II proteins are valuable factors that protect against cytokine-induced CNS injury.

Research paper thumbnail of Vitamin E-Supplemented Diets Reduce Lipid Peroxidation but Do Not Alter Either Pituitary-Adrenal, Glucose, and Lactate Responses to Immobilization Stress or Gastric Ulceration

Research paper thumbnail of Site-specific targeting of autoimmunity in mice induced by the localized production of IL-6

The Faseb Journal, Mar 1, 2008

Research paper thumbnail of Transgenic mice with astrocyte-targeted production of interleulcin-6 are resistant to high-fat diet-induced increases in body weight and body fat

Brain Behavior and Immunity, 2010

Research paper thumbnail of Non-Gaussian corrections to the probability distribution of the curvature perturbation from inflation

Jcap, 2006

We show how to obtain the probability density function for the amplitude of the curvature perturb... more We show how to obtain the probability density function for the amplitude of the curvature perturbation, \mathcal {R} , produced during an epoch of slow-roll, single-field inflation, working directly from n-point correlation functions of \mathcal {R} . These n-point functions are the usual output of quantum field theory calculations, and as a result we bypass approximate statistical arguments based on the central limit theorem. Our method can be extended to deal with arbitrary forms of non-Gaussianity, appearing at any order in the n-point hierarchy. We compute the probability density for the total smoothed perturbation within a Hubble volume, epsi, and for the spectrum of epsi. When only the two-point function is retained, exact Gaussian statistics are recovered. For when the three-point function is taken into account, we compute explicitly the leading slow-roll correction to the Gaussian result.

Research paper thumbnail of Distribution of metallothionein I + II and vesicular zinc in the developing central nervous system: Correlative study in the rat

The Journal of Comparative Neurology, Sep 20, 1999

Because zinc (Zn) is a co-factor in enzymes and participates in neurotransmission, it is essentia... more Because zinc (Zn) is a co-factor in enzymes and participates in neurotransmission, it is essential for brain development. However, because excess Zn may cause neuronal injury, cerebral mechanisms for Zn regulation must operate. The metallothionein isoforms I and II (MT I + II) are putative candidates for chelating unbound Zn released from Zn-containing nerve terminals or transported into the brain. Whether vesicular Zn and MT I + II occur in identical regions of the developing brain is unknown. Accordingly, the developmental distribution of MT I + II and vesicular Zn was mapped. By using double-labeling fluorescence histochemistry, MT I + II immunoreactivity (ir) was attributed to astrocytes and cells of myelomonocytic lineage. The cells of the myelomonocytic lineage shared the morphology of monocytes and macrophages but not of microglia and occurred primarily around vessels and ventricles in the brainstem. By contrast, astrocytes were widespread throughout the developing brain. In embryonic and neonatal brain, MT I + IIir astrocytes were almost selectively observed in the septum and fascia dentate hilus (hi) of the hippocampus. With increasing postnatal age, they also occurred in hippocampal cortex, basal forebrain, neocortex, cerebellar cortex, and cranial nerve nuclei. MT I + II mRNAs were detected in regions of the brain that also displayed MT I + IIir, indicating transcriptional events. Vesicular Zn was recorded in neonatal brain solely in the dentate hi of the hippocampus. With increasing age, the amount of vesicular Zn increased in the hippocampus and other forebrain regions. The presence of MT I + II proteins in the developing brain was confirmed by radioimmunoassay. The regional distribution of astrocytic MT I + IIir and vesicular Zn suggests that MT I + II are implicated in Zn metabolism in the developing forebrain.

Research paper thumbnail of Astrocytic IL-6 Influences the Clinical Symptoms of EAE in Mice

Brain Sciences, 2016

Interleukin-6 (IL-6) is a multifunctional cytokine that not only plays major roles in the immune ... more Interleukin-6 (IL-6) is a multifunctional cytokine that not only plays major roles in the immune system, but also serves as a coordinator between the nervous and endocrine systems. IL-6 is produced in multiple cell types in the CNS, and in turn, many cells respond to it. It is therefore important to ascertain which cell type is the key responder to IL-6 during both physiological and pathological conditions. In order to test the role of astrocytic IL-6 in neuroinflammation, we studied an extensively-used animal model of multiple sclerosis, experimental autoimmune encephalomyelitis (EAE), in mice with an IL-6 deficiency in astrocytes (Ast-IL-6 KO). Results indicate that lack of astrocytic IL-6 did not cause major changes in EAE symptomatology. However, a delay in the onset of clinical signs was observed in Ast-IL-6 KO females, with fewer inflammatory infiltrates and decreased demyelination and some alterations in gliosis and vasogenesis, compared to floxed mice. These results suggest that astrocyte-secreted IL-6 has some roles in EAE pathogenesis, at least in females.

Research paper thumbnail of PGC-1 is not mandatory for exercise- and training-induced adaptive gene responses in mouse skeletal muscle

Amer J Physiol Endocrinol Met, 2007

Research paper thumbnail of Metallothionein Treatment Reduces Proinflammatory Cytokines IL-6 and TNF-α and Apoptotic Cell Death during Experimental Autoimmune Encephalomyelitis (EAE)

Experimental Neurology, Jul 31, 2001

Research paper thumbnail of Phosphodiesterase 5 inhibition at disease onset prevents experimental autoimmune encephalomyelitis progression through immunoregulatory and neuroprotective actions

Experimental Neurology, Nov 6, 2013

Research paper thumbnail of Metallothionein-mediated antioxidant defense system and its response to exercise training are impaired in human type 2 diabetes. Diabetes 2005;54:3089–3094

Research paper thumbnail of Expression of growth inhibitory factor (metallothionein-III) mRNA and protein following excitotoxic immature brain injury

Journal of Neuropathology and Experimental Neurology, May 1, 1999

The balance between trophic factors and inhibitory molecules is likely to determine the outcome o... more The balance between trophic factors and inhibitory molecules is likely to determine the outcome of neural tissue damage. The growth inhibitory factor (GIF), a member of the metallothionein family of proteins named metallothionein-III (MT-III), has been suggested to play an important role in tissue repair after adult brain injury. Because no information is available on this factor in relation to immature brain damage, we examined the chronological changes of GIF (MT-III) mRNA and protein following excitotoxic lesions to the postnatal day 9 brain using in situ hybridization and immunocytochemical techniques. We observed a significant decrease of neuronal GIF (MT-III) mRNA and protein levels between 4 and 24 hours postinjury and an increase in glial GIF (MT-III) levels. Double immunocytochemical techniques showed GIF (MT-III) and GFAP positive astrocytes from 2-4 hours postinjury. From 3 days postinjury strongly reactive astrocytes expressed strong levels of both GIF (MT-III) mRNA and protein, which were maintained in the glial scar formed at longer times. These results show the expression of an inhibitory molecule by postnatal reactive astrocytes. Glial GIF (MT-III) expression may play an important role in the tissue reconstruction after immature brain damage.

Research paper thumbnail of Hypoxic Preconditioning Induces Neuroprotective Stanniocalcin-1 in Brain via IL-6 Signaling

Research paper thumbnail of The pupal morphology of the Carabus (s. l.) (Coleoptera, Carabidae) of the southwestern Iberian peninsula

Animal Biodiversity and Conservation, 2002

Research paper thumbnail of Role of Glucocorticoids on Rat Brain Metallothionein-I and-III Response to Stress

The metallothionein (MT) gene family consists of four members (MT-I through -IV) that are tightly... more The metallothionein (MT) gene family consists of four members (MT-I through -IV) that are tightly regulated during development. Whereas MT-I and MT-II are widely expressed isoforms, MT-III has been found to be mainly expressed in the central nervous system in adult animals, and is the only isoform that inhibits survival and neurite formation of cortical neurons in vitro. A number of models of brain injury have been shown to affect MT-III mRNA levels, which has been suggested to be related to the putative neurotrophic role of this protein. However, a stress response will presumably be associated to the brain injury which could, in turn, drive MT-III regulation. In the present report the effect of a classical stress model, immobilization stress, on brain MT regulation has been studied in rats. MT-I+II protein levels were measured by radioimmunoassay in up to eight brain areas and, as expected, it was found that stress increased selectively MT-I+II levels. Adrenalectomy (ADX) had a general decreasing effect on basal MT-I+II levels; however, ADX blunted the MT-I+II response to stress in cerebellum and presumably in frontal cortex and medulla plus pons but not in the hypothalamus. MT-I mRNA measurements were in accordance with the MT-I+II protein levels in the brain areas studied. In contrast to MT-I mRNA, MT-III mRNA levels of brain cortex tended to decrease during stress, although this effect was not statistically significant. ADX also tended to decrease basal MT-III mRNA levels. Northern blot assays of pooled mRNAs suggested similar differential regulation of these two brain MT isoforms in the cerebellum. These results indicate that glucocorticoids mediate brain MT-I+II response to stress in some but not all brain areas, that a role of these hormones is likely also for MT-III, and that the regulation of MT isoforms differs substantially in the brain.

Research paper thumbnail of Interleukin-6 regulation of ΑΜP-activated protein kinase : Potential role in the systemic response to exercise and prevention of the metabolic syndrome