QUÉ ES LA NEUROFARMACOLOGÍA?
Estudio de los fármacos desde el punto de vista neuroquímico,
lo que comprende el descubrimiento, el diseño, la identificación
y preparación de compuestos biológicamente activos, la
interpretación de su modo de interacción a nivel molecular,
la construcción de su relación estructura-actividad y
el estudio de su metabolismo.
ARTÍCULOS RECOMENDADOS
 |
Alterations
on phosphodiesterase type 7 and 8 isozyme mRNA expression in Alzheimer’s
disease brains examined by in situ hybridization.
|
S.Perez-Torres,
R.Cortés, M.Tolnay, A.Probst, J.M. Palacios, and G. Mengoda.
Department of Neurochemistry IIBB/CSIC (IDIBAPS) c/Rosselló161,
6, E-08036 Barcelona, Spain. Institute of Pathology Department of Neuropathology
University Hospital Basel, Basel, Switzerland.
Received 25 July 2002; revised 26 November 2002.
Accepted 12 December 2002.
Abstract
Phosphodiesterases (PDEs) play a central role
in signal transduction by regulating intracellular levels of cyclic
AMP (cAMP) and cGMP.
It has been suggested that cAMP pathways could be upregulated in Alzheimer’s
disease. By in situ hybridization histochemistry we have determined
the expression pattern of two newly described cAMP-specific phosphodiesterases
families, PDE7 and PDE8, in several brain areas in control subjects.
The hybridization levels of PDE8A mRNA were very low in all brain areas
examined. High PDE7B and PDE8B mRNA signal intensities were found in
the hippocampal formation. PDE7A was found to be present in both neuronal
and non-neuronal cell populations. When the expression of these isozymes
in control brains was compared with that in Alzheimer’s disease
brains staged according to Braak and Braak (Acta Neuropathol. (Berl.)
82 (1991), 239), we found that PDE8B was the only isozyme showing a
significant increase, in cortical areas and parts of the hippocampal
formation, at Braak stages III–VI. Our results show that the expression
of specific cAMP PDE isoforms is selectively regulated in Alzheimer’s
disease and associated with the stages of the disease. The availability
of animal models of Alzheimer’s disease and of new pharmacological
tools such as selective PDE inhibitors will allow study of the therapeutic
potential of thecontrol of cAMP levels in AD.
© 2003 Elsevier Science (USA). All rights reserved.
Keywords: cAMP signaling; PDE7A; PDE7B; PDE8B; mRNA localization;
Alzheimer’s disease, Braak stage.
|
Neuronal
Expression of cAMP-Specific Phosphodiesterase 7B mRNA in the rat
brain. |
E.Reyes-Irisarri,
S.Pérez-Torres and G.Mengod.
Department of NeurochemistryInstitut d’Investigacions Biomèdiques
de Barcelona. Consejo Superior de Investigaciones Científicas
Institut d’Investigacions Biomèdiques August Pi i Sunyer
(IIBB-CSIC, IDIBAPS), c/Rosselló 161, 6a, E-08036 Barcelona,
Spain.
Abstract
cAMP plays an important role as second messenger
molecule controlling multiple cellular processes in the brain. cAMP
levels depend critically on the phosphodiesterases (PDE) activity, enzymes
responsible for the clearance of intracellular cAMP. We have examined
the regional distribution and cellular localization of mRNA coding for
the cAMPspecific phosphodiesterase 7B (PDE7B) in rat brain by in situ
hybridization histochemistry. PDE7B mRNA is specifically distributed
in rat brain, preferentially in neuronal cell populations.
The highest levels of hybridization are observed in olfactory tubercle,
islands of Calleja, dentate gyrus, caudateputamen and some thalamic
nuclei. Positive hybridization signals are also detected in other areas,
such as cerebral cortex, Purkinje cells of the cerebellum and area postrema.
By double in situ hybridization histochemistry, we found that 74% and
79% of the cells expressing PDE7B mRNA in striatum and olfactory tubercle,
respectively, were GABAergic cells (expressing glutamic acid decarboxylase
mRNA), in contrast with the lack of expression in the few cholinergic
cells (expressing choline acetyltransferase mRNA) present in those two
areas (around 0.4% in olfactory tubercle). In the thalamic nuclei, a
majority of cells containing PDE7B mRNA also expresses a glutamatergic
marker (76.7% express vesicular glutamate transporter vGluT1 and 76%
express vGluT2 mRNAs). Almost all PDE7B expressing cells in dentate
gyrus (93%) were glutamatergic.
These results offer a neuroanatomical and neurochemical base that will
support the search for specific functions for cAMP dependent PDEs and
for the development of specific PDE7 inhibitors.
© 2005 IBRO. Published by Elsevier Ltd. All rights reserved.
Keywords: in situ hybridization, PDE, glutamatergic cells, GABAergic
cells, cholinergic cells.
|
Expression
of serotonin 5-HT2C receptors in GABAergic cells of the anterior
raphe nuclei. |
Jordi
Serrats, Guadalupe Mengod, Roser Cortés.
Department of Neurochemistry, Institut d’Investigacions Biomèdiques
de Barcelona (IIBB)–CSIC (IDIBAPS), Rosselló 161, 6th floor,
E-08036-Barcelona, Spain.
Received 24 October 2003
Received in revised form 27 March 2004
Accepted 27 March 2004
Available online 8 December 2004
Abstract
We have used double in situ hybridization to examine
the cellular localization of 5-HT2C receptor mRNA in relation to serotonergic
and
GABAergic neurons in the anterior raphe nuclei of the rat. In the dorsal
and median raphe nuclei 5-HT2C receptor mRNAwas not detected in serotonergic
cells identified as those expressing serotonin (5-HT) transporter mRNA.
In contrast, 5-HT2C receptor mRNAwas found in most GABAergic cells,
recognized by the presence of glutamic acid decarboxylase mRNA. Such
5-HT2C receptor-positive GABAergic neurons were mainly located in the
intermediolateral and lateral portions of the dorsal raphe and lateral
part of the median raphe. The present data give anatomical support to
a previous hypothesis that proposed a negative-feedback loop involving
reciprocal connections between GABAergic interneurons bearing 5-HT2A/2C
receptors and 5-HT neurons in the dorsal raphe and surrounding areas.
According to this model, the excitation of GABAergic interneurons through
these 5-HT2C (and also 5-HT2A) receptors would result in the suppression
of 5-HT cell firing.
© 2004 Elsevier B.V. All rights reserved.
Keywords: Dorsal raphe; Median raphe; GAD; 5-HT transporter; Serotonergic
lesions; 5,7-DHT; In situ hybridization.
