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1.
Biofabrication ; 7(2): 025005, 2015 May 07.
Article in English | MEDLINE | ID: mdl-25947357

ABSTRACT

The tympanic membrane (TM) is a thin tissue able to efficiently collect and transmit sound vibrations across the middle ear thanks to the particular orientation of its collagen fibers, radiate on one side and circular on the opposite side. Through the combination of advanced scaffolds and autologous cells, tissue engineering (TE) could offer valuable alternatives to autografting in major TM lesions. In this study, a multiscale approach based on electrospinning (ES) and additive manufacturing (AM) was investigated to fabricate scaffolds, based on FDA approved copolymers, resembling the anatomic features and collagen fiber arrangement of the human TM. A single scale TM scaffold was manufactured using a custom-made collector designed to confer a radial macro-arrangement to poly(lactic-co-glycolic acid) electrospun fibers during their deposition. Dual and triple scale scaffolds were fabricated combining conventional ES with AM to produce poly(ethylene oxide terephthalate)/poly(butylene terephthalate) block copolymer scaffolds with anatomic-like architecture. The processing parameters were optimized for each manufacturing method and copolymer. TM scaffolds were cultured in vitro with human mesenchymal stromal cells, which were viable, metabolically active and organized following the anisotropic character of the scaffolds. The highest viability, cell density and protein content were detected in dual and triple scale scaffolds. Our findings showed that these biomimetic micro-patterned substrates enabled cell disposal along architectural directions, thus appearing as promising substrates for developing functional TM replacements via TE.


Subject(s)
Biomimetics , Lactic Acid/chemistry , Polyglycolic Acid/chemistry , Tissue Engineering , Tissue Scaffolds , Bone Marrow Cells/cytology , Cell Survival , Cells, Cultured , Humans , Mesenchymal Stem Cells/cytology , Microscopy, Electron, Scanning , Polylactic Acid-Polyglycolic Acid Copolymer , Porosity , Tympanic Membrane/anatomy & histology , Tympanic Membrane/pathology
2.
J Biomed Mater Res A ; 103(10): 3284-92, 2015 Oct.
Article in English | MEDLINE | ID: mdl-25809157

ABSTRACT

As the endothelium still represents the ideal surface for cardiovascular devices, different endothelialization strategies have been attempted for biocompatibility and nonthrombogenicity enhancement. Since endothelial progenitor cells (EPCs) could accelerate endothelialization, preventing thrombosis and restenosis, the aim of this study was to use oligonucleotides (ONs) to biofunctionalize stents for EPC binding. In order to optimize the functionalization procedure before its application to cobalt-chromium (Co/Cr) stents, discs of the same material were preliminarily used. Surface aminosilanization was assessed by infrared spectroscopy and scanning electron microscopy. A fluorescent endothelial-specific ON was immobilized on aminosilanized surfaces and its presence was visualized by confocal microscopy. Fluorescent ON binding to porcine blood EPCs was assessed by flow cytometry. Viability assay was performed on EPCs cultured on unmodified, nontargeting ON or specific ON-coated discs; fluorescent staining of nuclei and F-actin was then performed on EPCs cultured on unmodified or specific ON-coated discs and stents. Disc biofunctionalization significantly increased EPC viability as compared to both unmodified and nontargeting ON-coated surfaces; cell adhesion was also significantly increased. Stents were successfully functionalized with the specific ON, and EPC binding was confirmed by confocal microscopy. In conclusion, stent biofunctionalization for EPC binding was successfully achieved in vitro, suggesting its use to obtain in vivo endothelialization, exploiting the natural regenerative potential of the human body.


Subject(s)
Chromium Alloys/chemistry , Endothelial Cells/metabolism , Materials Testing , Oligonucleotides/chemistry , Stem Cells/metabolism , Stents , Animals , Cell Adhesion , Humans , Swine
3.
Chempluschem ; 80(3): 490-493, 2015 Mar.
Article in English | MEDLINE | ID: mdl-31973409

ABSTRACT

A novel nanoconstruct based on poly(lactic-co-glycolic acid) nanoparticles loaded with a tetrathiahelicene molecule conjugated to a fluorescent rhodamine probe was prepared and characterized. Because helicenes are known to be very promising DNA intercalators, the tetrathiahelicene was selected for this study as a model therapeutic cytotoxic molecule. The ability of the nanoconstruct to internalize the tetrathiahelicene and deliver it intracellularly in a safe manner has been investigated by means of cytotoxicity and cell uptake tests on Balb/3T3 clone A31 fibroblasts. The outcomes of this study suggest the suitability of the developed nanoconstruct to act as a vector for the intracellular delivery of hydrophobic small molecules, such as helicenes, thus contributing to their possible future exploitation as novel therapeutics.

4.
Int J Pharm ; 475(1-2): 523-35, 2014 Nov 20.
Article in English | MEDLINE | ID: mdl-25178828

ABSTRACT

Poly(ester-ether-urethane)s copolymers are a resourceful class of biopolymers for the preparation of nanocarriers for drug delivery applications. However, a simple clinical translation for this synthetic material with biological and quality features is still needed. In this view, poly(ε-caprolactone)-co-poly(ethylene glycol) copolymers were synthesized as semi-bulk pilot (Kg) scale under mild conditions in absence of catalyst, bearing functional termini such as fluorescein tag and anticancer targeting moieties. The obtained materials were processed into surface decorated paclitaxel (PTX) loaded nanoparticles (NPs). The NPs were fully characterized in vitro and in vivo biodistribution in healthy mice evidenced no sign of toxicity and lower levels of PTX in lung and spleen, compared to clinically applied PTX dosage form.


Subject(s)
Antineoplastic Agents, Phytogenic/chemistry , Nanoparticles/chemistry , Paclitaxel/chemistry , Animals , Antineoplastic Agents, Phytogenic/administration & dosage , Antineoplastic Agents, Phytogenic/pharmacokinetics , BALB 3T3 Cells , Mice , Paclitaxel/administration & dosage , Paclitaxel/pharmacokinetics , Polyesters/chemistry , Polyethylene Glycols , Polyurethanes , Tissue Distribution
5.
Tissue Eng Part C Methods ; 19(12): 911-24, 2013 Dec.
Article in English | MEDLINE | ID: mdl-23537352

ABSTRACT

The traditional bone tissue-engineering approach exploits mesenchymal stem cells (MSCs) to be seeded once only on three-dimensional (3D) scaffolds, hence, differentiated for a certain period of time and resulting in a homogeneous osteoblast population at the endpoint. However, after achieving terminal osteodifferentiation, cell viability is usually markedly compromised. On the other hand, naturally occurring osteogenesis results from the coexistence of MSC progenies at distinct differentiative stages in the same microenvironment. This diversification also enables long-term viability of the mature tissue. We report an easy and tunable in vitro method to engineer simple osteogenic cell niches in a biomimetic fashion. The niches were grown via periodic reseeding of undifferentiated MSCs on MSC/scaffold constructs, the latter undergoing osteogenic commitment. Time-fractioning of the seeded cell number during differentiation time of the constructs allowed graded osteogenic cell populations to be grown together on the same scaffolds (i.e., not only terminally differentiated osteoblasts). In such cell-dynamic systems, the overall differentiative stage of the constructs could also be tuned by varying the cell density seeded at each inoculation. In this way, we generated two different biomimetic niche models able to host good reservoirs of preosteoblasts and other osteoprogenitors after 21 culture days. At that time, the niche type resulting in 40.8% of immature osteogenic progenies and only 59.2% of mature osteoblasts showed a calcium content comparable to the constructs obtained with the traditional culture method (i.e., 100.03 ± 29.30 vs. 78.51 ± 28.50 pg/cell, respectively; p=not significant), the latter colonized only by fully differentiated osteoblasts showing exhausted viability. This assembly method for tissue-engineered constructs enabled a set of important parameters, such as viability, colonization, and osteogenic yield of the MSCs to be balanced on 3D scaffolds, thus achieving biomimetic in vitro models with graded osteogenicity, which are more complex and reliable than those currently used by tissue engineers.


Subject(s)
Biomimetic Materials , Bone Substitutes , Cell Differentiation , Mesenchymal Stem Cells , Osteogenesis , Tissue Scaffolds , Cells, Cultured , Female , Humans , Male , Mesenchymal Stem Cells/cytology , Mesenchymal Stem Cells/metabolism
6.
Biomed Microdevices ; 14(6): 1115-27, 2012 Dec.
Article in English | MEDLINE | ID: mdl-22767245

ABSTRACT

An Additive Manufacturing technique for the fabrication of three-dimensional polymeric scaffolds, based on wet-spinning of poly(ε-caprolactone) (PCL) or PCL/hydroxyapatite (HA) solutions, was developed. The processing conditions to fabricate scaffolds with a layer-by-layer approach were optimized by studying their influence on fibres morphology and alignment. Two different scaffold architectures were designed and fabricated by tuning inter-fibre distance and fibres staggering. The developed scaffolds showed good reproducibility of the internal architecture characterized by highly porous, aligned fibres with an average diameter in the range 200-250 µm. Mechanical characterization showed that the architecture and HA loading influenced the scaffold compressive modulus and strength. Cell culture experiments employing MC3T3-E1 preosteoblast cell line showed good cell adhesion, proliferation, alkaline phosphatase activity and bone mineralization on the developed scaffolds.


Subject(s)
Bone and Bones/chemistry , Polymers/chemistry , Tissue Engineering/methods , Tissue Scaffolds/chemistry , 3T3 Cells , Alkaline Phosphatase/metabolism , Animals , Anthraquinones/metabolism , Biocompatible Materials , Cell Adhesion , Cell Proliferation , Cell Survival , Durapatite/metabolism , Equipment Design/methods , Materials Testing , Mice , Microscopy, Confocal , Microscopy, Electron, Scanning , Polyesters/metabolism , Porosity , Reproducibility of Results
7.
J Colloid Interface Sci ; 374(1): 308-14, 2012 May 15.
Article in English | MEDLINE | ID: mdl-22341699

ABSTRACT

A novel and simple method for the preparation of chemically functionalized boron nitride nanotubes (BNNTs) is presented. Thanks to a strong oxidation followed by the silanization of the surface through 3-aminopropyl-triethoxysilane (APTES), BNNTs exposing amino groups on their surface were successfully obtained. The efficacy of the procedure was assessed with EDS and XPS analyses, which demonstrated a successful functionalization of ~15% boron sites. This approach opens interesting perspectives for further modification of BNNTs with several kinds of molecules. Since, in particular, biomedical applications are envisaged, we also demonstrated in vitro biocompatibility and cellular up-take of the functionalized BNNTs.


Subject(s)
Biocompatible Materials/chemical synthesis , Boron Compounds/chemistry , Nanotubes/chemistry , Silanes/chemistry , Animals , Biocompatible Materials/pharmacology , Boron Compounds/pharmacology , Cell Survival/drug effects , Electrochemical Techniques , Mice , Microscopy, Electron, Scanning , NIH 3T3 Cells , Nanotubes/ultrastructure , Oxidation-Reduction , Photoelectron Spectroscopy , Propylamines
8.
Materials (Basel) ; 4(3): 527-542, 2011 Mar 01.
Article in English | MEDLINE | ID: mdl-28880003

ABSTRACT

This research activity was aimed at the development of dual-scale scaffolds consisting of three-dimensional constructs of aligned poly(ε-caprolactone) (PCL) microfilaments and electrospun poly(lactic-co-glycolic acid) (PLGA) fibers. PCL constructs composed by layers of parallel microsized filaments (0/90° lay-down pattern), with a diameter of around 365 µm and interfilament distance of around 191 µm, were produced using a melt extrusion-based additive manufacturing technique. PLGA electrospun fibers with a diameter of around 1 µm were collected on top of the PCL constructs with different thicknesses, showing a certain degree of alignment. Cell culture experiments employing the MC3T3 murine preosteoblast cell line showed good cell viability and adhesion on the dual-scale scaffolds. In particular, the influence of electrospun fibers on cell morphology and behavior was evident, as well as in creating a structural bridging for cell colonization in the interfilament gap.

9.
Curr Pharm Biotechnol ; 12(2): 275-84, 2011 Feb 01.
Article in English | MEDLINE | ID: mdl-21050164

ABSTRACT

Few animal model studies have been conducted in order to evaluate the impact of androgenic anabolic steroids (AAS) supraphysiological doses on the cardiovascular system and myocardial injury. Twenty-five male CD1 mice (8-10 weeks old; 35g initial body weight) were randomized into three AAS treated groups and two control groups. The AAS mice received intramuscular Nandrolone Decanoate (DECA-DURABOLIN), vehicled in arachidis oil, for 42 days, twice per week, with different dosages, studying plasma lipid analysis, cardiac histopathological features, cardiac ß (1) adrenergic receptor expression, and the effects of the myocardial expression of inflammatory mediators (IL-1ß, TNF-α) on the induction of cardiomyocytes apoptosis (HSP 70, TUNEL), using proteomic and immunohistochemical analysis. The mice had free movements in their animal rooms (two groups) or exercised by running on a motor-driven treadmill the others three groups. Recurring high dose AAS administration and physical training in mice produce significant increase in body weight and for total cholesterol. A moderate increase of the heart weight, cardiac hypertrophy and wide colliquative myocytolysis, were observed in high dose AAS administration and physical training group. The expression of HSP70 and inflammatory cytokine IL-1ß, increased in the three AAS-treated groups. TNF- α showed a more extensive expression in the AAS-high dose group. A significant apoptotic process randomly sparse in the myocardium was described. Our data support the hypothesis that the combined effects of vigorous training, anabolic steroid abuse and stimulation of the sympathetic nervous system, may predispose to myocardial injury.


Subject(s)
Anabolic Agents/pharmacology , Cytokines/biosynthesis , Heart/drug effects , Nandrolone/analogs & derivatives , Physical Conditioning, Animal , Receptors, Adrenergic, beta-1/biosynthesis , Tumor Necrosis Factor-alpha/biosynthesis , Anabolic Agents/administration & dosage , Anabolic Agents/toxicity , Animals , Apoptosis/drug effects , Cytokines/metabolism , Heart/physiopathology , In Situ Nick-End Labeling , Lipids/blood , Male , Mice , Models, Animal , Myocardium/metabolism , Nandrolone/administration & dosage , Nandrolone/pharmacology , Nandrolone/toxicity , Nandrolone Decanoate , Random Allocation , Tumor Necrosis Factor-alpha/metabolism
10.
J Mater Sci Mater Med ; 21(5): 1761-9, 2010 May.
Article in English | MEDLINE | ID: mdl-20135202

ABSTRACT

Novel polymeric micro-nanostructure meshes as blood vessels substitute have been developed and investigated as a potential solution to the lack of functional synthetic small diameter vascular prosthesis. A commercial elastomeric polyurethane (Tecoflex EG-80A) and a natural biopolymer (gelatin) were successfully co-electrospun from different spinnerets on a rotating mandrel to obtain composite meshes benefiting from the mechanical characteristics of the polyurethane and the natural biopolymer cytocompatibility. Morphological analysis showed a uniform integration of micrometric (Tecoflex) and nanometric (gelatin) fibers. Exposure of the composite meshes to vapors of aqueous glutaraldehyde solution was carried out, to stabilize the gelatin fibers in an aqueous environment. Uniaxial tensile testing in wet conditions demonstrated that the analyzed Tecoflex-Gelatin specimens possessed higher extensibility and lower elastic modulus than conventional synthetic grafts, providing a closer matching to native vessels. Biological evaluation highlighted that, as compared with meshes spun from Tecoflex alone, the electrospun composite constructs enhanced endothelial cells adhesion and proliferation, both in terms of cell number and morphology. Results suggest that composite Tecoflex-Gelatin meshes could be promising alternatives to conventional vascular grafts, deserving of further studies on both their mechanical behaviour and smooth muscle cell compatibility.


Subject(s)
Blood Vessel Prosthesis , Gelatin/chemistry , Bioprosthesis , Elasticity , Endothelial Cells , Humans , Myocytes, Smooth Muscle , Polyurethanes , Prostheses and Implants
11.
J Mater Sci Mater Med ; 21(1): 343-51, 2010 Jan.
Article in English | MEDLINE | ID: mdl-19653069

ABSTRACT

Polycaprolactone/hydroxyapatite (PCL/HA) composites were prepared by in situ generation of HA in the polymer solution starting from the precursors calcium nitrate tetrahydrate and ammonium dihydrogen phosphate via sol-gel process. Highly interconnected porosity was achieved by means of the salt-leaching technique using a mixture of sodium chloride and sodium bicarbonate as porogens. Structure and morphology of the PCL/HA composites were investigated by scanning electron microscopy, and mechanical properties were determined by means of tensile and compression tests. The possibility to employ the developed composites as scaffolds for bone tissue regeneration was assessed by cytotoxicity test of the PCL/HA composites extracts and cell adhesion and proliferation in vitro studies.


Subject(s)
Bone and Bones/physiology , Durapatite/chemistry , Polyesters/chemistry , Tissue Scaffolds/chemistry , Animals , BALB 3T3 Cells , Biomechanical Phenomena , Bone and Bones/cytology , Bone and Bones/drug effects , Cell Adhesion/drug effects , Cell Adhesion/physiology , Cell Proliferation/drug effects , Cells, Cultured , Durapatite/chemical synthesis , Materials Testing , Mice , Microscopy, Electron, Transmission , Phase Transition , Porosity , Tissue Engineering/methods , Water/pharmacology
12.
Acta Biomater ; 6(4): 1258-68, 2010 Apr.
Article in English | MEDLINE | ID: mdl-19683605

ABSTRACT

Poly(lactic-co-glycolic acid) (PLGA) meshes loaded with retinoic acid (RA) were prepared by applying the electrospinning technique. The purpose of the present work was to combine the biological effects of RA and the advantages of electrospun meshes to enhancing the mass transfer features of controlled release systems and cell interaction with polymeric scaffolds. The processing conditions for the fabrication of three-dimensional meshes were optimized by studying their influence on mesh morphology. Tensile testing showed that RA loading influenced the meshes' mechanical properties by increasing their strength and rigidity. Moreover, the drug release and degradation profiles of the electrospun systems were compared to analogous RA-loaded PLGA films prepared by solvent casting. The results of this study highlight that the electrospun meshes preserved their fibrous structure after 4 months under in vitro physiological conditions and showed a sustained controlled release of the loaded agent in comparison to that observed for cast films. The bioactivity of the loaded RA was investigated on murine preosteoblasts cells by evaluating its influence on cell proliferation and morphology.


Subject(s)
Delayed-Action Preparations/metabolism , Glycolates/chemistry , Materials Testing/methods , Tissue Scaffolds/chemistry , Tretinoin/metabolism , Animals , Cell Line , Cell Proliferation/drug effects , Electricity , Glycolates/pharmacology , Lactic Acid , Mice , Microscopy, Confocal , Microscopy, Electron, Scanning , Molecular Weight , Polyglycolic Acid , Polylactic Acid-Polyglycolic Acid Copolymer , Solutions , Spectrophotometry, Ultraviolet , Temperature , Tensile Strength/drug effects
13.
Int J Biomater ; 2009: 239643, 2009.
Article in English | MEDLINE | ID: mdl-20126577

ABSTRACT

The most promising approach in Tissue Engineering involves the seeding of porous, biocompatible/biodegradable scaffolds, with donor cells to promote tissue regeneration. Additive biomanufacturing processes are increasingly recognized as ideal techniques to produce 3D structures with optimal pore size and spatial distribution, providing an adequate mechanical support for tissue regeneration while shaping in-growing tissues. This paper presents a novel extrusion-based system to produce 3D scaffolds with controlled internal/external geometry for TE applications.The BioExtruder is a low-cost system that uses a proper fabrication code based on the ISO programming language enabling the fabrication of multimaterial scaffolds. Poly(epsilon-caprolactone) was the material chosen to produce porous scaffolds, made by layers of directionally aligned microfilaments. Chemical, morphological, and in vitro biological evaluation performed on the polymeric constructs revealed a high potential of the BioExtruder to produce 3D scaffolds with regular and reproducible macropore architecture, without inducing relevant chemical and biocompatibility alterations of the material.

14.
Int J Pharm ; 343(1-2): 90-7, 2007 Oct 01.
Article in English | MEDLINE | ID: mdl-17580105

ABSTRACT

Bioeliminable co-polymers based on poly(methacryloylglycylglycine-OH(x)-co-hydroxypropylmethacrylamide(y)) were successfully converted into nanoparticles by using the co-precipitation technique. Human serum albumin (HSA) and a modified (beta-cyclodextrin were used, respectively, as model protein drug and stabilizer. Nanoparticles were characterized from a dimensional and morphological point of view by means of laser diffraction granulometry and scanning electron microscopy (SEM). The prepared nanoparticles displayed a monomodal diameter distribution in the range of 130 nm, confirmed by SEM micrographs. Protein loading efficiency and drug release kinetics investigations, carried out on bioeliminable nanoparticles loaded with fluoresceinated HSA (HSA-FITC), showed that protein loading is in the range of 60% with a typical time controlled release profile. In vitro cytotoxicity investigations of the polymer matrices and resulting nanoparticles were carried out by using different assays aimed at the evaluation of the interactions of the materials with cell metabolism and the cell membrane. On the whole, bioeliminable polymers and nanoparticles resulted in high cytocompatibility thus suggesting their suitability for biomedical applications.


Subject(s)
Drug Delivery Systems , Nanoparticles/administration & dosage , Polymethacrylic Acids/administration & dosage , Serum Albumin/administration & dosage , Animals , BALB 3T3 Cells , Cell Proliferation/drug effects , Cell Survival/drug effects , Humans , Mice , Microscopy, Electron, Scanning , Nanoparticles/chemistry , Nanoparticles/toxicity , Nanoparticles/ultrastructure , Polymethacrylic Acids/chemistry , Polymethacrylic Acids/toxicity , Proteins , Serum Albumin/chemistry , Serum Albumin/toxicity
15.
J Neurochem ; 91(2): 285-98, 2004 Oct.
Article in English | MEDLINE | ID: mdl-15447662

ABSTRACT

Elucidation of the biochemical steps leading to the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced degeneration of the nigrostriatal dopamine (DA) pathway has provided new clues to the pathophysiology of Parkinson's disease. In line with the enhancement of MPTP toxicity by diethyldithiocarbamate (DDC), here we demonstrate how other cytochrome P450 (CYP) 2E1 inhibitors, such as diallyl sulphide (DAS) and phenylethylisothiocyanate (PIC), also potentiate the selective DA neurone degeneration in C57/bl mice. In addition, we show that CYP 2E1 is present in the brain and in the basal ganglia of this mouse strain, as measured by RT-PCR, western blot analysis and immunohistochemistry. A kinetic analysis of MPTP and its metabolites, by means of the microdialysis technique in the striatum, indicates that no detoxification metabolic pathway is affected by any of these inhibitors. This does not rule out, however, that an undetected detoxification pathway involving CYP 2E1 is operating. In order to provide direct evidence for this isozyme involvement, CYP 2E1 knockout mice were challenged with MPTP or the combined treatment. Here we show that these transgenic mice have a low sensitivity to MPTP alone, similar to their wild-type counterparts, suggesting that it is likely that transgenic mice compensate for the missing enzyme. However, DDC pretreatment completely fails to enhance MPTP toxicity in CYP 2E1 knockout mice, whereas this enhancement is regularly present in wild-type animals. This study indicates that the occurrence of CYP 2E1 in C57/bl mouse brain is relevant to MPTP toxicity, and suggests that this isozyme may have a detoxificant role related to the efflux transporter of the toxin.


Subject(s)
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine , Cytochrome P-450 CYP2E1/metabolism , Parkinsonian Disorders/chemically induced , Parkinsonian Disorders/enzymology , 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine/metabolism , 3,4-Dihydroxyphenylacetic Acid/metabolism , Allyl Compounds/pharmacology , Animals , Blotting, Western , Cytochrome P-450 CYP2E1/genetics , Cytochrome P-450 CYP2E1 Inhibitors , Disease Models, Animal , Ditiocarb/pharmacology , Dopamine/metabolism , Drug Synergism , Enzyme Inhibitors/pharmacology , Male , Mice , Mice, Inbred C57BL , Mice, Knockout , Microdialysis , Neostriatum/drug effects , Neostriatum/metabolism , Neostriatum/pathology , Parkinsonian Disorders/pathology , Reverse Transcriptase Polymerase Chain Reaction , Substantia Nigra/drug effects , Substantia Nigra/metabolism , Substantia Nigra/pathology , Sulfides/pharmacology , Tyrosine 3-Monooxygenase/biosynthesis
16.
Brain Res ; 948(1-2): 192-202, 2002 Sep 06.
Article in English | MEDLINE | ID: mdl-12383975

ABSTRACT

We have recently shown that tyrosine-hydroxylase immunostaining (TH-IM) is selectively decreased in the cingulate cortex and in the shell of the nucleus accumbens (nAcc) of Sardinian alcohol-preferring rats (sP) when compared with Sardinian alcohol-non preferring (sNP) and Wistar (W) rats. Since these regions contain both dopamine and noradrenaline (NA) fibers, clarification of the dopaminergic and noradrenergic contribution to the decreased TH-immunoreactivity was needed. To this aim, we carried out the present immunohistochemistry study using two antibodies raised against dopamine beta-hydroxylase (DBH), the enzyme responsible for the conversion of dopamine into noradrenaline, and against the dopamine transporter (DAT), as markers for noradrenergic and dopaminergic fibers, respectively. The results show that DBH-immunostaining (DBH-IM) and DAT-immunostaining (DAT-IM) were both lower in the cingulate cortex of the sP rats with respect to sNP and W rats. In the shell of the nAcc a reduced DAT-IM in sP rats was found, while the DBH-IM did not differ between the three lines of rats. The analysis of the cell-body area of noradrenergic neurons in the locus coeruleus, revealed no differences between sP, sNP and W rats. These results indicate a selective reduction of the terminal innervation in the mesocorticolimbic dopamine and NA systems in sP rats. This genetically-determined difference may be involved in the opposite alcohol preference and consumption of sP and sNP rats.


Subject(s)
Alcohol Drinking/metabolism , Alcohol-Related Disorders/metabolism , Dopamine beta-Hydroxylase/metabolism , Limbic System/metabolism , Membrane Glycoproteins , Membrane Transport Proteins/metabolism , Nerve Tissue Proteins , Animals , Dopamine/metabolism , Dopamine Plasma Membrane Transport Proteins , Gyrus Cinguli/cytology , Gyrus Cinguli/metabolism , Immunohistochemistry , Limbic System/cytology , Locus Coeruleus/cytology , Locus Coeruleus/metabolism , Norepinephrine/metabolism , Nucleus Accumbens/cytology , Nucleus Accumbens/metabolism , Rats , Rats, Inbred Strains , Rats, Wistar
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