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  1. Article ; Online: Reelin expression in brain endothelial cells: an electron microscopy study.

    Perez-Costas, Emma / Fenton, Erin Y / Caruncho, Hector J

    BMC neuroscience

    2015  Volume 16, Page(s) 16

    Abstract: Background: Reelin expression and function have been extensively studied in the brain, although its expression has been also reported in other tissues including blood. This raises the possibility that reelin might be able to cross the blood-brain ... ...

    Abstract Background: Reelin expression and function have been extensively studied in the brain, although its expression has been also reported in other tissues including blood. This raises the possibility that reelin might be able to cross the blood-brain barrier, which could be functionally relevant. Up-to-date no studies have been conducted to assess if reelin is present in the blood-brain barrier, which is mainly constituted by tightly packed endothelial cells. In this report we assessed the expression of reelin in brain capillaries using immunocytochemistry and electron microscopy.
    Results: At the light microscope, reelin immunolabeling appeared in specific endothelial cells in brain areas that presented abundant diffuse labeling for this protein (e.g., layer I of the cortex, or the stratum lacunosum moleculare of the hippocampus), while it was mostly absent from capillaries in other brain areas (e.g., deeper cortical layers, or the CA1 layer of the hippocampus). As expected, at the electron microscope reelin labeling was observed in neurons of the cortex, where most of the labeling was associated with the rough endoplasmic reticulum. Importantly, reelin was also observed in some endothelial cells located in small capillaries, which confirmed the findings obtained at the light microscope. In these cells, reelin labeling was located primarily in caveolae (i.e., vesicles of transcytosis), and associated with the plasma membrane of the luminal side of endothelial cells. In addition, some scarce labeling was observed in the nuclear membrane.
    Conclusions: The presence of reelin immunolabeling in brain endothelial cells, and particularly in caveolar vesicles within these cells, suggests that reelin and/or reelin peptides may be able to cross the blood-brain barrier, which could have important physiological, pathological, and therapeutic implications.
    MeSH term(s) Animals ; Blood-Brain Barrier/metabolism ; Blood-Brain Barrier/ultrastructure ; Brain/blood supply ; Brain/metabolism ; Brain/ultrastructure ; Capillaries/metabolism ; Capillaries/ultrastructure ; Cell Adhesion Molecules, Neuronal/metabolism ; Endothelial Cells/metabolism ; Endothelial Cells/ultrastructure ; Extracellular Matrix Proteins/metabolism ; Immunohistochemistry ; Male ; Microscopy, Electron ; Nerve Tissue Proteins/metabolism ; Photomicrography ; Rats ; Serine Endopeptidases/metabolism
    Chemical Substances Cell Adhesion Molecules, Neuronal ; Extracellular Matrix Proteins ; Nerve Tissue Proteins ; Serine Endopeptidases (EC 3.4.21.-) ; reelin protein (EC 3.4.21.-)
    Language English
    Publishing date 2015-03-24
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ISSN 1471-2202
    ISSN (online) 1471-2202
    DOI 10.1186/s12868-015-0156-4
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Preserving independence among under-resourced older adults in the Southeastern United States: existing barriers and potential strategies for research.

    Enogela, Ene M / Buchanan, Taylor / Carter, Christy S / Elk, Ronit / Gazaway, Shena B / Goodin, Burel R / Jackson, Elizabeth A / Jones, Raymond / Kennedy, Richard E / Perez-Costas, Emma / Zubkoff, Lisa / Zumbro, Emily L / Markland, Alayne D / Buford, Thomas W

    International journal for equity in health

    2022  Volume 21, Issue 1, Page(s) 119

    Abstract: Disability prevention and preservation of independence is crucial for successful aging of older adults. To date, relatively little is known regarding disparities in independent aging in a disadvantaged older adult population despite widely recognized ... ...

    Abstract Disability prevention and preservation of independence is crucial for successful aging of older adults. To date, relatively little is known regarding disparities in independent aging in a disadvantaged older adult population despite widely recognized health disparities reported in other populations and disciplines. In the U.S., the Southeastern region also known as "the Deep South", is an economically and culturally unique region ravaged by pervasive health disparities - thus it is critical to evaluate barriers to independent aging in this region along with strategies to overcome these barriers. The objective of this narrative review is to highlight unique barriers to independent aging in the Deep South and to acknowledge gaps and potential strategies and opportunities to fill these gaps. We have synthesized findings of literature retrieved from searches of computerized databases and authoritative texts. Ultimately, this review aims to facilitate discussion and future research that will help to address the unique challenges to the preservation of independence among older adults in the Deep South region.
    MeSH term(s) Aged ; Aging ; Humans ; Southeastern United States ; United States ; Vulnerable Populations
    Language English
    Publishing date 2022-08-27
    Publishing country England
    Document type Journal Article ; Review ; Research Support, N.I.H., Extramural
    ZDB-ID 2092056-8
    ISSN 1475-9276 ; 1475-9276
    ISSN (online) 1475-9276
    ISSN 1475-9276
    DOI 10.1186/s12939-022-01721-5
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Preserving independence among under-resourced older adults in the Southeastern United States

    Ene M. Enogela / Taylor Buchanan / Christy S. Carter / Ronit Elk / Shena B. Gazaway / Burel R. Goodin / Elizabeth A. Jackson / Raymond Jones / Richard E. Kennedy / Emma Perez-Costas / Lisa Zubkoff / Emily L. Zumbro / Alayne D. Markland / Thomas W. Buford

    International Journal for Equity in Health, Vol 21, Iss 1, Pp 1-

    existing barriers and potential strategies for research

    2022  Volume 15

    Abstract: Abstract Disability prevention and preservation of independence is crucial for successful aging of older adults. To date, relatively little is known regarding disparities in independent aging in a disadvantaged older adult population despite widely ... ...

    Abstract Abstract Disability prevention and preservation of independence is crucial for successful aging of older adults. To date, relatively little is known regarding disparities in independent aging in a disadvantaged older adult population despite widely recognized health disparities reported in other populations and disciplines. In the U.S., the Southeastern region also known as “the Deep South”, is an economically and culturally unique region ravaged by pervasive health disparities – thus it is critical to evaluate barriers to independent aging in this region along with strategies to overcome these barriers. The objective of this narrative review is to highlight unique barriers to independent aging in the Deep South and to acknowledge gaps and potential strategies and opportunities to fill these gaps. We have synthesized findings of literature retrieved from searches of computerized databases and authoritative texts. Ultimately, this review aims to facilitate discussion and future research that will help to address the unique challenges to the preservation of independence among older adults in the Deep South region.
    Keywords Aging ; Independence ; Southeastern United states ; Health disparities ; Disability ; Public aspects of medicine ; RA1-1270
    Language English
    Publishing date 2022-08-01T00:00:00Z
    Publisher BMC
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article ; Online: The intracellular angiotensin system buffers deleterious effects of the extracellular paracrine system.

    Villar-Cheda, Begoña / Costa-Besada, Maria A / Valenzuela, Rita / Perez-Costas, Emma / Melendez-Ferro, Miguel / Labandeira-Garcia, Jose L

    Cell death & disease

    2017  Volume 8, Issue 9, Page(s) e3044

    Abstract: The 'classical' renin-angiotensin system (RAS) is a circulating system that controls blood pressure. Local/paracrine RAS, identified in a variety of tissues, including the brain, is involved in different functions and diseases, and RAS blockers are ... ...

    Abstract The 'classical' renin-angiotensin system (RAS) is a circulating system that controls blood pressure. Local/paracrine RAS, identified in a variety of tissues, including the brain, is involved in different functions and diseases, and RAS blockers are commonly used in clinical practice. A third type of RAS (intracellular/intracrine RAS) has been observed in some types of cells, including neurons. However, its role is still unknown. The present results indicate that in brain cells the intracellular RAS counteracts the intracellular superoxide/H
    MeSH term(s) Aging/genetics ; Aging/metabolism ; Angiotensin II/metabolism ; Angiotensin II/pharmacology ; Animals ; Blood Pressure/physiology ; Cell Line ; Cell Nucleus/drug effects ; Cell Nucleus/metabolism ; Cell Nucleus/ultrastructure ; Dopaminergic Neurons/drug effects ; Dopaminergic Neurons/metabolism ; Dopaminergic Neurons/ultrastructure ; Gene Expression Regulation ; Humans ; Hydrogen Peroxide/metabolism ; Insulin-Like Growth Factor I/genetics ; Insulin-Like Growth Factor I/metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Paracrine Communication/physiology ; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha/genetics ; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha/metabolism ; Primary Cell Culture ; Rats, Sprague-Dawley ; Receptor, Angiotensin, Type 2/genetics ; Receptor, Angiotensin, Type 2/metabolism ; Renin-Angiotensin System/genetics ; Sirtuin 1/genetics ; Sirtuin 1/metabolism ; Substantia Nigra/cytology ; Substantia Nigra/drug effects ; Substantia Nigra/metabolism ; Superoxides/metabolism
    Chemical Substances Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha ; Ppargc1a protein, mouse ; Receptor, Angiotensin, Type 2 ; Superoxides (11062-77-4) ; Angiotensin II (11128-99-7) ; Insulin-Like Growth Factor I (67763-96-6) ; Hydrogen Peroxide (BBX060AN9V) ; Sirt1 protein, mouse (EC 3.5.1.-) ; Sirtuin 1 (EC 3.5.1.-)
    Language English
    Publishing date 2017-09-07
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2541626-1
    ISSN 2041-4889 ; 2041-4889
    ISSN (online) 2041-4889
    ISSN 2041-4889
    DOI 10.1038/cddis.2017.439
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Assessment of cytochrome C oxidase dysfunction in the substantia nigra/ventral tegmental area in schizophrenia.

    Rice, Matthew W / Smith, Kristen L / Roberts, Rosalinda C / Perez-Costas, Emma / Melendez-Ferro, Miguel

    PloS one

    2014  Volume 9, Issue 6, Page(s) e100054

    Abstract: Perturbations in metabolism are a well-documented but complex facet of schizophrenia pathology. Optimal cellular performance requires the proper functioning of the electron transport chain, which is constituted by four enzymes located within the inner ... ...

    Abstract Perturbations in metabolism are a well-documented but complex facet of schizophrenia pathology. Optimal cellular performance requires the proper functioning of the electron transport chain, which is constituted by four enzymes located within the inner membrane of mitochondria. These enzymes create a proton gradient that is used to power the enzyme ATP synthase, producing ATP, which is crucial for the maintenance of cellular functioning. Anomalies in a single enzyme of the electron transport chain are sufficient to cause disruption of cellular metabolism. The last of these complexes is the cytochrome c oxidase (COX) enzyme, which is composed of thirteen different subunits. COX is a major site for oxidative phosphorylation, and anomalies in this enzyme are one of the most frequent causes of mitochondrial pathology. The objective of the present report was to assess if metabolic anomalies linked to COX dysfunction may contribute to substantia nigra/ventral tegmental area (SN/VTA) pathology in schizophrenia. We tested COX activity in postmortem SN/VTA from schizophrenia and non-psychiatric controls. We also tested the protein expression of key subunits for the assembly and activity of the enzyme, and the effect of antipsychotic medication on subunit expression. COX activity was not significantly different between schizophrenia and non-psychiatric controls. However, we found significant decreases in the expression of subunits II and IV-I of COX in schizophrenia. Interestingly, these decreases were observed in samples containing the entire rostro-caudal extent of the SN/VTA, while no significant differences were observed for samples containing only mid-caudal regions of the SN/VTA. Finally, rats chronically treated with antipsychotic drugs did not show significant changes in COX subunit expression. These findings suggest that COX subunit expression may be compromised in specific sub-regions of the SN/VTA (i.e. rostral regions), which may lead to a faulty assembly of the enzyme and a greater vulnerability to metabolic insult.
    MeSH term(s) Adult ; Aged ; Aged, 80 and over ; Animals ; Antipsychotic Agents/pharmacology ; Autopsy ; Electron Transport Complex IV/metabolism ; Female ; Humans ; Male ; Middle Aged ; Mitochondria/drug effects ; Mitochondria/enzymology ; Oxidative Phosphorylation/drug effects ; Rats ; Schizophrenia/drug therapy ; Schizophrenia/enzymology ; Schizophrenia/pathology ; Substantia Nigra/drug effects ; Substantia Nigra/enzymology ; Substantia Nigra/pathology ; Ventral Tegmental Area/drug effects ; Ventral Tegmental Area/enzymology ; Ventral Tegmental Area/pathology
    Chemical Substances Antipsychotic Agents ; Electron Transport Complex IV (EC 1.9.3.1)
    Language English
    Publishing date 2014-06-18
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ISSN 1932-6203
    ISSN (online) 1932-6203
    DOI 10.1371/journal.pone.0100054
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Mapping dopaminergic deficiencies in the substantia nigra/ventral tegmental area in schizophrenia.

    Rice, Matthew W / Roberts, Rosalinda C / Melendez-Ferro, Miguel / Perez-Costas, Emma

    Brain structure & function

    2014  Volume 221, Issue 1, Page(s) 185–201

    Abstract: Previous work from our laboratory showed deficits in tyrosine hydroxylase protein expression within the substantia nigra/ventral tegmental area (SN/VTA) in schizophrenia. However, little is known about the nature and specific location of these deficits ... ...

    Abstract Previous work from our laboratory showed deficits in tyrosine hydroxylase protein expression within the substantia nigra/ventral tegmental area (SN/VTA) in schizophrenia. However, little is known about the nature and specific location of these deficits within the SN/VTA. The present study had two aims: (1) test if tyrosine hydroxylase deficits could be explained as the result of neuronal loss; (2) assess if deficits in tyrosine hydroxylase are sub-region specific within the SN/VTA, and thus, could affect specific dopaminergic pathways. To achieve these objectives: (1) we obtained estimates of the number of dopaminergic neurons, total number of neurons, and their ratio in matched SN/VTA schizophrenia and control samples; (2) we performed a qualitative assessment in SN/VTA schizophrenia and control matched samples that were processed simultaneously for tyrosine hydroxylase immunohistochemistry. We did not find any significant differences in the total number of neurons, dopaminergic neurons, or their ratio. Our qualitative study of TH expression showed a conspicuous decrease in labeling of neuronal processes and cell bodies within the SN/VTA, which was sub-region specific. Dorsal diencephalic dopaminergic populations of the SN/VTA presented the most conspicuous decrease in TH labeling. These data support the existence of pathway-specific dopaminergic deficits that would affect the dopamine input to the cortex without significant neuronal loss. Interestingly, these findings support earlier reports of decreases in tyrosine hydroxylase labeling in the target areas for this dopaminergic input in the prefrontal and entorhinal cortex. Finally, our findings support that tyrosine hydroxylase deficits could contribute to the hypodopaminergic state observed in cortical areas in schizophrenia.
    MeSH term(s) Adult ; Aged ; Aged, 80 and over ; Cell Count ; Dopamine/metabolism ; Dopaminergic Neurons/metabolism ; Dopaminergic Neurons/pathology ; Female ; Humans ; Male ; Middle Aged ; Schizophrenia/metabolism ; Schizophrenia/pathology ; Substantia Nigra/metabolism ; Substantia Nigra/pathology ; Tyrosine 3-Monooxygenase/metabolism ; Ventral Tegmental Area/metabolism ; Ventral Tegmental Area/pathology
    Chemical Substances Tyrosine 3-Monooxygenase (EC 1.14.16.2) ; Dopamine (VTD58H1Z2X)
    Language English
    Publishing date 2014-10-01
    Publishing country Germany
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 2273162-3
    ISSN 1863-2661 ; 1863-2653
    ISSN (online) 1863-2661
    ISSN 1863-2653
    DOI 10.1007/s00429-014-0901-y
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: An accurate method for the quantification of cytochrome C oxidase in tissue sections.

    Melendez-Ferro, Miguel / Rice, Matthew W / Roberts, Rosalinda C / Perez-Costas, Emma

    Journal of neuroscience methods

    2013  Volume 214, Issue 2, Page(s) 156–162

    Abstract: Cytochrome oxidase (COX) is the enzyme that constitutes the last step of the mitochondrial electron transport chain for the production of ATP. Measurement of COX activity can be achieved by histochemistry, thus providing information about the metabolic ... ...

    Abstract Cytochrome oxidase (COX) is the enzyme that constitutes the last step of the mitochondrial electron transport chain for the production of ATP. Measurement of COX activity can be achieved by histochemistry, thus providing information about the metabolic status of the brain. Brain regions with high metabolism will present high COX activity in histochemistry assays and vice versa. Using histochemistry versus biochemistry to assess COX activity presents the advantage of providing a map of the differences in metabolism in discrete brain regions. Moreover, COX histochemistry allows quantifying the activity of a particular brain region, by converting units of optical density into units of activity. In the present work we have devised a methodology that allows not only quantifying differences in COX activity between groups, but also quantifying the amount of COX present in brain tissue sections, by directly relating optical density (OD) measurements to cytochrome C oxidase concentration, something that traditionally is achieved by the use of western blot. For this purpose we created a set of standards of known concentration of COX that were affixed to a nitrocellulose membrane, and this membrane was incubated together with the tissue sections in which COX activity was assessed. A standard curve was created using a gradient of different concentrations of purified bovine heart cytochrome oxidase (from 2μg to 0.1μg in intervals of 0.25μg). This standard curve allowed us to detect changes in optical density as low as 5%, and relate these OD differences with known concentrations of cytochrome C oxidase.
    MeSH term(s) Aged ; Animals ; Cattle ; Electron Transport Complex IV/analysis ; Histocytochemistry/methods ; Humans ; Male ; Substantia Nigra/chemistry ; Substantia Nigra/enzymology ; Ventral Tegmental Area/chemistry ; Ventral Tegmental Area/enzymology
    Chemical Substances Electron Transport Complex IV (EC 1.9.3.1)
    Language English
    Publishing date 2013-01-30
    Publishing country Netherlands
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 282721-9
    ISSN 1872-678X ; 0165-0270
    ISSN (online) 1872-678X
    ISSN 0165-0270
    DOI 10.1016/j.jneumeth.2013.01.010
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Basal ganglia pathology in schizophrenia: dopamine connections and anomalies.

    Perez-Costas, Emma / Melendez-Ferro, Miguel / Roberts, Rosalinda C

    Journal of neurochemistry

    2010  Volume 113, Issue 2, Page(s) 287–302

    Abstract: Schizophrenia is a severe mental illness that affects 1% of the world population. The disease usually manifests itself in early adulthood with hallucinations, delusions, cognitive and emotional disturbances and disorganized thought and behavior. Dopamine ...

    Abstract Schizophrenia is a severe mental illness that affects 1% of the world population. The disease usually manifests itself in early adulthood with hallucinations, delusions, cognitive and emotional disturbances and disorganized thought and behavior. Dopamine was the first neurotransmitter to be implicated in the disease, and though no longer the only suspect in schizophrenia pathophysiology, it obviously plays an important role. The basal ganglia are the site of most of the dopamine neurons in the brain and the target of anti-psychotic drugs. In this review, we will start with an overview of basal ganglia anatomy emphasizing dopamine circuitry. Then, we will review the major deficits in dopamine function in schizophrenia, emphasizing the role of excessive dopamine in the basal ganglia and the link to psychosis.
    MeSH term(s) Animals ; Antiparkinson Agents/pharmacology ; Antiparkinson Agents/therapeutic use ; Basal Ganglia/drug effects ; Basal Ganglia/metabolism ; Basal Ganglia/pathology ; Dopamine/metabolism ; Humans ; Schizophrenia/drug therapy ; Schizophrenia/pathology
    Chemical Substances Antiparkinson Agents ; Dopamine (VTD58H1Z2X)
    Language English
    Publishing date 2010-01-20
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Review
    ZDB-ID 80158-6
    ISSN 1471-4159 ; 0022-3042 ; 1474-1644
    ISSN (online) 1471-4159
    ISSN 0022-3042 ; 1474-1644
    DOI 10.1111/j.1471-4159.2010.06604.x
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article: Impairments in cognition and neural precursor cell proliferation in mice expressing constitutively active glycogen synthase kinase-3.

    Pardo, Marta / King, Margaret K / Perez-Costas, Emma / Melendez-Ferro, Miguel / Martinez, Ana / Beurel, Eleonore / Jope, Richard S

    Frontiers in behavioral neuroscience

    2015  Volume 9, Page(s) 55

    Abstract: Brain glycogen synthase kinase-3 (GSK3) is hyperactive in several neurological conditions that involve impairments in both cognition and neurogenesis. This raises the hypotheses that hyperactive GSK3 may directly contribute to impaired cognition, and ... ...

    Abstract Brain glycogen synthase kinase-3 (GSK3) is hyperactive in several neurological conditions that involve impairments in both cognition and neurogenesis. This raises the hypotheses that hyperactive GSK3 may directly contribute to impaired cognition, and that this may be related to deficiencies in neural precursor cells (NPC). To study the effects of hyperactive GSK3 in the absence of disease influences, we compared adult hippocampal NPC proliferation and performance in three cognitive tasks in male and female wild-type (WT) mice and GSK3 knockin mice, which express constitutively active GSK3. NPC proliferation was ~40% deficient in both male and female GSK3 knockin mice compared with WT mice. Environmental enrichment (EE) increased NPC proliferation in male, but not female, GSK3 knockin mice and WT mice. Male and female GSK3 knockin mice exhibited impairments in novel object recognition, temporal order memory, and coordinate spatial processing compared with gender-matched WT mice. EE restored impaired novel object recognition and temporal ordering in both sexes of GSK3 knockin mice, indicating that this repair was not dependent on NPC proliferation, which was not increased by EE in female GSK3 knockin mice. Acute 1 h pretreatment with the GSK3 inhibitor TDZD-8 also improved novel object recognition and temporal ordering in male and female GSK3 knockin mice. These findings demonstrate that hyperactive GSK3 is sufficient to impair adult hippocampal NPC proliferation and to impair performance in three cognitive tasks in both male and female mice, but these changes in NPC proliferation do not directly regulate novel object recognition and temporal ordering tasks.
    Language English
    Publishing date 2015-03-04
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2452960-6
    ISSN 1662-5153
    ISSN 1662-5153
    DOI 10.3389/fnbeh.2015.00055
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  10. Article ; Online: Dopamine pathology in schizophrenia: analysis of total and phosphorylated tyrosine hydroxylase in the substantia nigra.

    Perez-Costas, Emma / Melendez-Ferro, Miguel / Rice, Matthew W / Conley, Robert R / Roberts, Rosalinda C

    Frontiers in psychiatry

    2012  Volume 3, Page(s) 31

    Abstract: Introduction: Despite the importance of dopamine neurotransmission in schizophrenia, very few studies have addressed anomalies in the mesencephalic dopaminergic neurons of the substantia nigra/ventral tegmental area (SN/VTA). Tyrosine hydroxylase (TH) ... ...

    Abstract Introduction: Despite the importance of dopamine neurotransmission in schizophrenia, very few studies have addressed anomalies in the mesencephalic dopaminergic neurons of the substantia nigra/ventral tegmental area (SN/VTA). Tyrosine hydroxylase (TH) is the rate-limiting enzyme for the production of dopamine, and a possible contributor to the anomalies in the dopaminergic neurotransmission observed in schizophrenia.
    Objectives: In this study, we had three objectives: (1) Compare TH expression (mRNA and protein) in the SN/VTA of schizophrenia and control postmortem samples. (2) Assess the effect of antipsychotic medications on the expression of TH in the SN/VTA. (3) Examine possible regional differences in TH expression anomalies within the SN/VTA.
    Methods: To achieve these objectives three independent studies were conducted: (1) A pilot study to compare TH mRNA and TH protein levels in the SN/VTA of postmortem samples from schizophrenia and controls. (2) A chronic treatment study was performed in rodents to assess the effect of antipsychotic medications in TH protein levels in the SN/VTA. (3) A second postmortem study was performed to assess TH and phosphorylated TH protein levels in two types of samples: schizophrenia and control samples containing the entire rostro-caudal extent of the SN/VTA, and schizophrenia and control samples containing only mid-caudal regions of the SN/VTA.
    Results and conclusion: Our studies showed impairment in the dopaminergic system in schizophrenia that could be mainly (or exclusively) located in the rostral region of the SN/VTA. Our studies also showed that TH protein levels were significantly abnormal in schizophrenia, while mRNA expression levels were not affected, indicating that TH pathology in this region may occur posttranscriptionally. Lastly, our antipsychotic animal treatment study showed that TH protein levels were not significantly affected by antipsychotic treatment, indicating that these anomalies are an intrinsic pathology rather than a treatment effect.
    Language English
    Publishing date 2012-04-09
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2564218-2
    ISSN 1664-0640 ; 1664-0640
    ISSN (online) 1664-0640
    ISSN 1664-0640
    DOI 10.3389/fpsyt.2012.00031
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