0000000000091222
AUTHOR
Giuseppa Mudo'
Acute intermittent nicotine treatment enhances proliferation of neuronal precursor cells in the subventricular zone (SVZ) of adult rat brain
Metabotropic glutamate (mGLU2/3) receptor agonist LY379268 stimulates the production of glial cell line-derived neurotrophic factor (GDNF) in the mouse striatum: in vivo analysis of GDNF Receptor (c-RET) related signal transduction pathways activation.
Neuronal FGFR1 transactivation by inducing FGFR1/5-HT1A heteroreceptor complexes formation
There are no clear data on the molecular mechanism by which the hippocampal 5-HT transmission contributes to the neuroprotective and antidepressant effects of 5-HT uptake blockers. Previously, we revealed that a 5-HT1A agonist may induce phosphorylation of FGFR1 and ERK1/2 in rat hippocampus independent of FGF-2, suggesting transactivation of FGFR1 tyrosine kinase in the absence of neurotrophic factor binding. As extension of previous work, using BRET analysis and coimmunoprecipitation in cellular models, FGFR1-5-HT1A heteroreceptor complexes have been demonstrated and agonist modulation characterized. In vitro assays on ERK1/2 phosphorylation in HEK cells and primary hippocampal cultures h…
No effects of low-intensity endurance exercise on muscle necrosis in the diaphragm of mdx mice
Duchenne muscular dystrophy (DMD) is characterized by progressive skeletal muscle weakness. We have previously shown that low-intensity endurance training prevented muscle damage (Frinchi et al, Int J Sports Med 2014). Since the effects of low-intensity endurance training on the the diaphragm in the mdx mouse model are unknown, in the same animals we investigated Cx39 protein levels (Western blotting) in homogenates of the diaphragm before and after training. Mdx and wild-type (WT) mice were randomly assigned to sedentary (mdx-S, n=17; WT-S, n=19) or trained (mdx-EX, n=14; WT-EX, n=16) groups. Low-intensity endurance training (running on a wheel) was done 5 days/week for 6 weeks at progress…
Activation of PGC-1 protect dopaminergic neurons in the MPTP mouse model of Parkinson’s disease
Peroxisome proliferator-activated receptor-gamma coactivator-1 (PGC-1) is a transcriptional coactivator that is a master regulator of oxidative stress and mitochondrial metabolism. Mitochondrial dysfunction and oxidative stress occur in Parkinson’s disease (PD), but little is known about the molecular mechanisms controlling these events. We report that transgenic mice overexpressing PGC-1 in dopaminergic neurons are resistant against cell degeneration induced by the neurotoxin MPTP. The increase in neuronal viability was accompanied by elevated levels of mitochondrial antioxidants SOD2 and Trx2 in the substantia nigra of transgenic mice. To modulate PGC-1, we employed the small molecula…
Brain expression and 3H-Guanosine binding analysis of novel G protein-coupled receptor for guanosine (GPR23/LPA4)
Several studies have shown that guanine-based purines exert biological effects on the central nervous system, possibly through membrane receptor. In a parallel work, we have identified the first guanosine G protein-coupled receptor GPR23, known as LPA4 receptor, involved in the modulation of guanosine-mediated antiproliferative effects in human glioma cell lines. Here, we performed in different brain areas the following studies: by PCR, the expression levels of GPR23; by [3H]-Guanosine radioligand binding assay, the binding properties of GPR23; by [35S] GTPγS binding assay, the receptor activation properties of guanosine. Among the examined areas, the cerebral cortex showed the highest GPR2…
Caratterizzazione di un meccanismo trofico, mediato dal FGF-2 e dal suo recettore FGFR1, nelle cellule staminali della zona subventricolare del cervello di ratto adulto
Study of molecular mechanism involved in neuronal plasticity induced by magnetic stimulation in cultured hippocampal neurons
Although a large number of investigations have shown that transcranial magnetic stimulation, a non-invasive method of brain stimulation with minimal side effects, is able to induce neuronal synaptic plastic change, very few studies have examined the molecular mechanisms of magnetic stimulation involved in synaptic plasticity. Since it is well known that neurotrophins and their receptors regulate synaptic strength and thereby mediate plasticity, in this study we have investigated the effects of low-frequency (1 Hz) magnetic stimulation, at different intensities, on the activation of neurotrophic factors receptors and relative intracellular pathways in primary cultures of hippocampal neurons.…
Group II metabotropic glutamate receptor activation increases brain derived neurotrophic factor expression in the mouse brain.
Recovery of damaged skeletal muscle in mdx mice by low-intensity endurance exercise
Regulation of gap junctional connexin expression in experimental temporal epilepsy
Identification of GPR23/LPA4 as a candidate G protein-coupled receptor for Guanosine
Defective dopaminergic control of contractility in colon from hypoxanthine‐guanine phosphoribosyltransferase deficient (HPRT‐) knockout mice
Different connexin genes are expressed in immuno-identified cell types during skeletal muscle differentiation.
Role of Bioactive Molecules on Neuroprotection, Oxidative Stress, and Neuroinflammation Modulation.
As the global population ages, the burden of neurodegenerative and neurological disorders is dramatically increasing [...]
FGFR1-5-HT1A receptor heterocomplexes: relevance for neuroplasticity and depression
Serotonin receptor agonist treatment induces transactivation of fibroblast growth factor receptor-1 (FGFR1) tyrosine kinase in the rat hippocampal neurons
Over the past decade, many examples of activation of receptor tyrosine kinases in response to G-protein coupled receptor signaling have been reported, indicating that there are alternative modes of receptor tyrosine kinase activation (transactivation) in the absence of neurotrophic factor binding. In the present work, we aimed to examine if 5-HT receptor subtype activation may induce fibroblast growth factor receptor-1 (FGFR1) phosphorylation through transactivation of tyrosine kinase. The study has been performed in young adult rats treated with the selective 5-HT1A receptor agonist 8-OHDPAT at the dose of 0.4 mg/kg/i.p.. FGFR1 phosphorylation was evaluated by immunoprecipitation and weste…
DELAYED DOWN-REGULATION OF ASTROGLIAL CONNEXIN EXPRESSION AFTER PROTRACTED SEIZURES
Effects of mild aerobic exercise training on the diaphragm in mdx mice
Mild endurance exercise training positively affects limb skeletal muscle in the mdx mice model of Duchenne Muscular Dystrophy (DMD). However, few and controversial data are available on the effects of mild exercise training on the diaphragm of mdx mice. The diaphragm was examined in mdx and wild type mice either under sedentary conditions (mdx-SD, WT-SD) or during mild exercise training (mdx-EX, WT-EX). At baseline and after 30 and 45 days of training (5 d/wk for 6 weeks), diaphragm muscle morphology and Cx39 protein were assessed. In addition, tissue levels of the chaperonin Hsp60 were measured at the same time points in gastrocnemius, quadriceps and diaphragm in each experimental group. A…
Characterization of a trophic mechanism mediated by FGF-2 and its receptor FGFR1 expressed in the precursor cells of the subventricular zone (SVZ) in the adult rat brain.
Identification and functional binding analysis of GPR23/! LPA4 as a candidate G protein-coupled receptor for Guanosine.
Several studies have shown that guanine-based purines exert biological effects on the central nervous system (CNS), possibly through membrane receptors, but at the present there are not reports related to the identification of such specific receptor(s). We have identified the first guanosine G protein-coupled receptor GPR23, also known as LPA4 receptor, involved in the modulation of guanosine-mediated antiproliferative effects in human glioma cell line (U87). We report that the silencing of GPR23 reduces significantly the antiproliferative effects of guanosine, while stably transfected cell clones over-expressing GPR23 increase sensitivity to guanosine. [3H] Guanosine radioligand binding as…
Neurotrophic systems promoting neurogenesis in the adult rat brain
ANTIPROLIFERATIVE EFFECTS OF GUANINE-BASED PURINES AND IDENTIFICATION OF A CANDIDATE RECEPTOR
METABOTROPHIC GLUTAMATE RECEPTORS (MGLUR1/5 AND MGLUR2/3) ACTIVATION BY AGONISTS TREATMENT INCREASES FGF-2 AND BDNF IN RAT AND MOUSE BRAIN AND INDUCES NEUROPROTECTION
No effect of low-intensity endurance exercise on muscle necrosis in the diaphragm of mdx mice.
Duchenne muscular dystrophy (DMD) is characterized by progressive skeletal muscle weakness. We have previously shown that low-intensity endurance training prevented muscle damage (Frinchi et al, Int J Sports Med 2014). Since the effects of low-intensity endurance training on the the diaphragm in the mdx mouse model are unknown, in the same animals we investigated C x39 protein levels (Western blotting) in homogenates of the diaphragm before and after training. Mdx and wild-type (WT) mice were randomly assigned to sedentary (mdx-S, n=17; WT-S, n=19) or trained (mdx-EX, n=14; WT-EX, n=16) groups. Low-intensity endurance training (running on a wheel) was done 5 days/week for 6 weeks at progres…
Regulation of neurogenesis in the adult brain
Different connexin genes are expressed in early and late phases of the regenerating process in adult skeletal muscles
Analysis of connexin (Cx36 and Cx45) expression in the carotid body, adrenal medulla and enteric neurons of both mouse and rat
Cx36 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…
Small airways in sedentary and endurance-trained dystrophic (mdx) mice.
The effects of mild endurance exercise training on the small airways in mdx mice are unknown. We compared epithelial thickness and turnover, apoptosis, and stress marker expression in small airways of mdx mice and wild-type (WT) controls, at rest and during exercise training. Mdx and WT mice were randomly assigned to sedentary (mdx-S, n=17; WT-S, n=19) or trained (mdx- EX, n=14; WT-EX, n=16) groups. Low-intensity endurance training (running on a wheel) was done 5 d/wk for 6 wk at progressively increasing speed (rpm from 16 to 24) and time (15 min to 1 h). Lungs were processed for light microscopy and periodic acid Schiff (PAS) staining. Hsp60 and PCNA were quantified by immunohistochemistry…
Pharmacological activation of group II metabotropic glutamate receptors enhances the production of glial cell line-derived neurotrophic factor in the mouse brain.
Involvement of cyclin-dependent kinase-5 in the kainic acid-mediated degeneration of glutamatergic synapses in the rat hippocampus.
Increased 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…
Group II Metabotropic Glutamate Receptor Activation Enhances the Production of Glial cell line-derived Neurotrophic Factor In the Mouse Brain
ACUTE INTERMITTENT NICOTINE TREATMENT ENHANCES PROLIFERATION OF NEURONAL PRECURSOR CELLS IN THE SUBVENTRICOLAR ZONE (SVZ) OF ADULT AND AGED RAT BRAIN
Expression of the rat connexin gene, rCx39, during skeletal muscle differentiation and regeneration
Attivazione dei recettori metabotropici per il Glutamato mGluR2/3 e regolazione dell'espressione del BDNF e NGF nel cervello di topo
Distinct pattern of Connexin gene expression during skeletal muscle regeneration in the adult rat.
Aim: The aim of present work was to test the hypothesis that Cx37, Cx39, Cx40, Cx43 and Cx45 expression could be regulated in adult regenerating skeletal muscle in response to injury promoting activation of satellite cells involved in myofibers repair and regeneration. Methods: Using in situ hybridization and immunohistochemistry procedures we examined the spatial and temporal expression pattern of above listed connexins in the regenerating gastrocnemious muscle following a mechanical injury. Results: Cx43 and Cx45 mRNA were up-regulated very early, by 3 hour following muscle injury, and were localised in satellite cells, M-cadherin positive cells, distributed around the area of lesion. Thr…
Antiproliferative effects of guanine-based purines and expression of a candidate receptor.
NEUROPROTECTIVE ACTION OF RESVERATROL AGAINST OXIDATIVE STRESS AND IN THE MOUSE MODEL OF PARKINSON'S DISEASE.
Acute intermittent nicotine treatment counteracts the reduced proliferation of the neuronal precursor cells of the subventricular zone (SVZ) in aged rat brain
FGF-2/FGFR neurotrophic system expression level does not give account for the age-related decline of neurogenesis in the rat brain.
Resveratrol increases DAT expression levels in the striatum of female mouse and its effect is mediated by estrogen receptors
Resveratrol (3,4',5-trihydroxystilbene, RSV), a phytoalexins with a stilbene skeleton, exhibits a wide range of biological actions that includes neuroprotective effect against neurodegenerative diseases. In a previous study on RSV neuroprotective effects in mouse Parkinson’s model, we unexpectedly observed an upregulation of DAT in the striatum of female mice treated with RSV. Here we aimed to study in depth the effect of RSV on DAT expression, and additionally to verify the potential involvement of estrogen receptor activation by RSV, according with its striking similarity to the synthetic estrogen diethylstilbestrol. Daily repeated injection of RSV (20 mg/kg i.p.) for four days led, eight…