121,947 research outputs found
Analysis of connexin (Cx36 and Cx45) expression in the carotid body, adrenal medulla and enteric neurons of both mouse and rat
No full textCx36 and Cx45 are considered the main connexins expressed in neuronal cells of central nervous system (Belluardo N. et al. Brain Res. 2000)), but at present no complete data are available on their expression in the neurons of crest-derived neuroendocrine organ, such as the adrenal medulla, the carotid body and the enteric nervous system. Therefore the present study was undertaken to evaluate using immunohistochemistry and western blotting procedures, both in rat and mouse, whether Cx36 and Cx45 were expressed in neuronal cells of the carotid body, adrenal medulla and myenteric plexus at ileum and colon level. In the carotid body of both mouse and rat only Cx45 was found expressed as diffuse punctate immunostaining. High amount of Cx36 expression was detected in the medulla and zona glomerulosa of mouse adrenal gland, but not in the rat. The Cx45 was found only in the mouse zona reticularis of adrenal gland cortex. Very low amount of Cx36 punctate immunostaining was found in the myenteric plexus of mouse colon and ileum but not in the rat. No Cx45 immunostaining was evidenced in the myenteric plexus of both mouse and rat, although it was found along the circular muscle of colon and ileum. Using western blotting analysis we confirmed for both Cx36 and Cx45 the results obtained by immunohistochemistry. Taken together our data increase our insight into types of gap-junctions localized in neuronal of sympatho-adrenal system and their different expression between species
Nicotinic receptor agonists as neuroprotective/neurotrophic drugs. Progress in molecular mechanisms
No full textIn the present work we reviewed recent advances concerning neuroprotective/neurotrophic effects of acute or chronic nicotine exposure, and the signalling pathways mediating these effects, including mechanisms implicated in nicotine addiction and nAChR desensitization. Experimental and clinical data largely indicate long-lasting effects of nicotine and nicotinic agonists that imply a neuroprotective/neurotrophic role of nAChR activation, involving mainly alpha 7 and alpha 4 beta 2 nAChR subtypes, as evidenced using selective nAChR agonists. Compounds interacting with neuronal nAChRs have the potential to be neuroprotective and treatment with nAChR agonists elicits long-lasting neurotrophic effects, e.g. improvement of cognitive performance in a variety of behavioural tests in rats, monkeys and humans. Nicotine addiction, which is mediated by interaction with nACh receptors, is believed to involve the modification of signalling cascades that modulate synaptic plasticity and gene expression. Desensitization, in addition to protecting cells from uncontrolled excitation, is recently considered as a form of signal plasticity. nAChR can generate these longe-lasting effects by elaboration of complex intracellular signals that mediate medium to long-term events crucial for neuronal maintenance, survival and regeneration. Although a comprehensive survey of the gene-based molecular mechanisms that underlie nicotine effects has yet not been performed a growing amount of data is beginning to improve our understanding of signalling mechanisms that lead to neurotrophic/neuroprotective responses. Evidence for an involvement of the fibroblast growth factor-2 gene in nAChR mechanisms mediating neuronal survival, trophism and plasticity has been obtained. However, more work is needed to establish the mechanisms involved in the effects of nicotinic receptor subtype activation from cognition-enhancing and neurotrophic effects to smoking behaviour and to determine more precisely the therapeutic objectives in potential nicotinic drug treatments of neurodegenerative diseases.In the present work we reviewed recent advances concerning neuroprotective/neurotrophic effects of acute or chronic nicotine exposure, and the signalling pathways mediating these effects, including mechanisms implicated in nicotine addiction and nAChR desensitization. Experimental and clinical data largely indicate long-lasting effects of nicotine and nicotinic agonists that imply a neuroprotective/neurotrophic role of nAChR activation, involving mainly alpha 7 and alpha 4 beta 2 nAChR subtypes, as evidenced using selective nAChR agonists. Compounds interacting with neuronal nAChRs have the potential to be neuroprotective and treatment with nAChR agonists elicits long-lasting neurotrophic effects, e.g. improvement of cognitive performance in a variety of behavioural tests in rats, monkeys and humans. Nicotine addiction, which is mediated by interaction with nACh receptors, is believed to involve the modification of signalling cascades that modulate synaptic plasticity and gene expression. Desensitization, in addition to protecting cells from uncontrolled excitation, is recently considered as a form of signal plasticity. nAChR can generate these longe-lasting effects by elaboration of complex intracellular signals that mediate medium to long-term events crucial for neuronal maintenance, survival and regeneration. Although a comprehensive survey of the gene-based molecular mechanisms that underlie nicotine effects has yet not been performed a growing amount of data is beginning to improve our understanding of signalling mechanisms that lead to neurotrophic/neuroprotective responses. Evidence for an involvement of the fibroblast growth factor-2 gene in nAChR mechanisms mediating neuronal survival, trophism and plasticity has been obtained. However, more work is needed to establish the mechanisms involved in the effects of nicotinic receptor subtype activation from cognition-enhancing and neurotrophic effects to smoking behaviour and to determine more precisely the therapeutic objectives in potential nicotinic drug treatments of neurodegenerative diseases
Increase in Bcl-2 phosphorylation and reduced levels of BH3-only Bcl-2 family proteins in kainic acid-mediated neuronal death in the rat brain
No full textKainic acid induces excitotoxicity and nerve cell degeneration in vulnerable regions of rat brain, most markedly in hippocampus and amygdala. Part of the cell death following kainic acid is apoptotic as shown by caspase 3 activation and chromatin condensation. Here we have studied the regulation of pro- and anti-apoptotic proteins belonging to the Bcl-2 family in rat hippocampus and amygdala by kainic acid in relationship to ensuing neuronal death. The pro-apoptotic protein Bax was up-regulated in hippocampus 6 h after kainic acid administration. The increase in Bax was followed by the appearance of TdT-mediated dUTP nick end labelling-positive cells which were prominent at 24 h. Immunohistochemistry for active Bax revealed a punctated labelling of neurons in the CA3 and hilar regions of hippocampus as well as in amygdala. Double staining for NeuN, a marker for nerve cells, and TdT-mediated dUTP nick end labelling showed that mainly neurons undergo degeneration after kainic acid treatment. In contrast to Bax, the pro-apoptotic BH3-only Bcl-2 proteins Bim and Harakiri/DP5 were down-regulated by kainic acid. This was also observed for the anti-apoptotic proteins Bcl-x and Bcl-w. Immunoreactive Bcl-2 was up-regulated in hippocampus after kainic acid together with an increase in the phosphorylation of serine-87 in Bcl-2, suggesting a post-transcriptional modification of the protein. This was confirmed using immunoprecipitation of total Bcl-2 from hippocampus and amygdala which revealed an increase in serine-87 phospho-Bcl-2 after kainic acid. Inhibition of the c-jun N-terminal protein kinase pathway reduced both serine-87 phosphorylation and cell death after kainic acid. This indicates an important role of Bcl-2 phosphorylation in controlling neuronal death after kainic acid. In contrast to the situation in trophic factor-deprived neurons, no up-regulation of Bim or Harakiri/DP5 proteins occurred after kainic acid, suggesting alternative pathways for regulation of cell death in excitotoxicity. The results indicate that not only the relative levels of Bcl-2 family proteins but also conformation changes and post-translational modifications contribute to neuronal death following kainic acid
Involvement of cyclin-dependent kinase-5 in the kainic acid-mediated degeneration of glutamatergic synapses in the rat hippocampus
No full textIncreased levels of glutamate causing excitotoxic damage accompany neurological disorders such as ischemia/stroke, epilepsy and some neurodegenerative diseases. Cyclin-dependent kinase-5 (Cdk5) is important for synaptic plasticity and is deregulated in neurodegenerative diseases. However, the mechanisms by which kainic acid (KA)-induced excitotoxic damage involves Cdk5 in neuronal injury are not fully understood. In this work, we have thus studied involvement of Cdk5 in the KA-mediated degeneration of glutamatergic synapses in the rat hippocampus. KA induced degeneration of mossy fiber synapses and decreased glutamate receptor (GluR)6/7 and post-synaptic density protein 95 (PSD95) levels in rat hippocampus in vivo after intraventricular injection of KA. KA also increased the cleavage of Cdk5 regulatory protein p35, and Cdk5 phosphorylation in the hippocampus at 12 h after treatment. Studies with hippocampal neurons in vitro showed a rapid decline in GluR6/7 and PSD95 levels after KA treatment with the breakdown of p35 protein and phosphorylation of Cdk5. These changes depended on an increase in calcium as shown by the chelators 1,2-bis(o-aminophenoxy)ethane-N,N,N ',N'-tetraacetic acid acetoxymethyl ester (BAPTA-AM) and glycol-bis (2-aminoethylether)-N,N,N ',N '-tetra-acetic acid. Inhibition of Cdk5 using roscovitine or employing dominant-negative Cdk5 and Cdk5 silencing RNA constructs counteracted the decreases in GluR6/7 and PSD95 levels induced by KA in hippocampal neurons. The dominant-negative Cdk5 was also able to decrease neuronal degeneration induced by KA in cultured neurons. The results show that Cdk5 is essentially involved in the KA-mediated alterations in synaptic proteins and in cell degeneration in hippocampal neurons after an excitotoxic injury. Inhibition of pathways activated by Cdk5 may be beneficial for treatment of synaptic degeneration and excitotoxicity observed in various brain diseases
mGluR2/3 agonist LY379268, by enhancing the production of GDNF, induces a time-related phosphorylation of RET receptor and intracellular signaling Erk1/2 in mouse striatum.
No full textIn the present study we aimed to verify if the enhancement of glial cell line-derived neurotrophic factor (GDNF) production in mouse striatum following treatment with LY379268 may also induce in the nigrostriatal system a time-related activation of RET receptor and its specific intracellular signaling. For this purpose, we have investigated the effects of LY379268 treatment on RET phosphorylation at the Tyr1062 and on downstream signaling Erk1/2, Akt and PLCγ1 pathway activation. The results showed that treatment with LY379268 (3 mg/kg) induces a significant increase of GDNF levels and time-related RET and Erk1/2 phosphorylation in the striatum. These increases were detected at 24 h and 48 h following LY379268 treatment. No changes were observed in the Akt and PLCγ1 phosphorylation levels. Similar results for p-Erk1/2 were observed in the substantia nigra. A complete block of LY379268 effect on striatal RET and p-Erk1/2 phosphorylation was observed in mice intrastriatal injected with anti-GDNF antibodies, suggesting a correlation between GDNF upregulation and RET activation. Overall, with present data we have shown that activation of mGluR2/3 receptors by LY379268 may be particularly promising for nigrostriatal dopaminergic system protection by enhancing striatal levels of GDNF/RET trophic system activity
Nicotine-induced FGF-2 mRNA in rat brain is preserved during aging
No full textIndirect trophic actions of nicotine on brain during aging are suggested from observations describing nicotine as a cognitive enhancer, increasing vigilance and improving learning and memory, and both in vitro and in vivo models have demonstrated neuroprotective effects of nAChR agonists. Previously, we have reported that an acute intermittent (-)nicotine treatment significantly increases fibroblast growth factor-2 (FGF-2) mRNA and protein in several brain regions of rat brain. The present study was designed to analyse if nicotine-induced FGF-2 expression in the rat brain was preserved during aging. Using in situ hybridization and quantitative RNase protection assay the present paper reports that during aging (12- and 24-month-old rats) the response of FGF-2 gene expression in the rat brain to nAChR stimulation by (-)nicotine is fully effective and involves both neurons and glial cells. The investigation was extended to other members of the FGF family, such as FGF-5 and -20, but this expression was not influenced by the (-)nicotine treatment at any age studied. Similarly following (-)nicotine treatment no changes were observed in FGF receptors (FGFR 1-3) mRNA levels in adult and aged rats. Taken together, the present and previous data support the hypothesis that neuroprotective effects of (-)nicotine and the potential beneficial effects of (-)nicotine agonists in the treatment of Alzheimer''s and Parkinson''s diseases, may at least in part involve an activation of the neuronal and glial FGF-2 signalling. Work is in progress to analyse the mechanism(s) linking nAChR activation to the up-regulation of FGF-2
Effetti della stimolazione elettrica della regione tubero-infundibolare dell'ipotalamo sulla moltiplicazione cellulare dell'epitelio delle ghiandole dell'intestino tenue nel ratto.
No full textExpression of the rat connexin gene, rCx39, during skeletal muscle differentiation and regeneration
No full textActivité mitotique dans l'épithélium des glandes de l'intestin grele du Rat après électrothermocoagulation de le région tubéro-infundibulaire de l'hypothalamus et résection simultanée de la glande pinéale.
No full textEffect of cerebral hemisphere decortication on the cytotoxic activity of natural killer and natural cytotoxic lymphocytes in the mouse
No full textA comparison was made of the effects of left and right cerebral decortication on cytotoxic activity of natural killer and natural cytotoxic lymphocytes in the mouse. Natural killer cytotoxic activity was significantly reduced after right decortication, whereas left decortication led to a less pronounced, though still significant fall. The cytotoxic activity of natural cytotoxic cells, on the other hand, was significantly i increased, particularly 15 days after left decortication. These findings mirror the results of previously published personal findings following electrothermocoagulation of the hypothalamus. The suggestion is made that the cortex and the hypothalamus form an integrated system for the control of certain aspects of natural immunity
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