INVESTIGADORES
CALVO Daniel Juan
artículos
Título:
Identification of brain neurons expressing the dopamine D4 receptor gene using BAC transgenic mice.
Autor/es:
NOAIN, D.; AVALE, M. E.; WEDEMEYER, C.; DANIEL JUAN CALVO; PEPER, M.; RUBINSTEIN, M.
Revista:
European Journal of Neuroscience
Editorial:
Blackwell Publishing
Referencias:
Lugar: Londres; Año: 2006 vol. 24 p. 2429 - 2438
Resumen:
The dopamine D4 receptor (D4R) has received considerable interest because of its higher affinity for atypical antipsychotics, the
extremely polymorphic nature of the human gene and the genetic association with attention deficit and hyperactivity disorder (ADHD).
Several efforts have been undertaken to determine the D4R expression pattern in the brain using immunohistochemistry, binding
autoradiography and in situ hybridization, but the overall published results present large discrepancies. Here, we have explored an
alternative genetic approach by studying bacterial artificial chromosome (BAC) transgenic mice that express enhanced green
fluorescent protein (EGFP) under the transcriptional control of the mouse dopamine D4 receptor gene (Drd4). Immunohistochemical
analysis performed in brain sections of Drd4-EGFP transgenic mice using an anti-EGFP polyclonal antibody showed that transgenic
expression was predominant in deep layer neurons of the prefrontal cortex, particularly in the orbital, prelimbic, cingulate and rostral
agranular portions. In addition, discrete groups of Drd4-EGFP labelled neurons were observed in the anterior olfactory nucleus,
ventral pallidum, and lateral parabrachial nucleus. EGFP was not detected in the striatum, hippocampus or midbrain as described
using other techniques. Given the fine specificity of EGFP expression in BAC transgenic mice and the high sensitivity of the EGFP
antibody used in this study, our results indicate that Drd4 expression in the adult mouse brain is limited to a more restricted number of
areas than previously reported. Its leading expression in the prefrontal cortex supports the importance of the D4R in complex
behaviours depending on cortical dopamine (DA) transmission and its possible role in the etiopathophysiology of ADHD.in situ hybridization, but the overall published results present large discrepancies. Here, we have explored an
alternative genetic approach by studying bacterial artificial chromosome (BAC) transgenic mice that express enhanced green
fluorescent protein (EGFP) under the transcriptional control of the mouse dopamine D4 receptor gene (Drd4). Immunohistochemical
analysis performed in brain sections of Drd4-EGFP transgenic mice using an anti-EGFP polyclonal antibody showed that transgenic
expression was predominant in deep layer neurons of the prefrontal cortex, particularly in the orbital, prelimbic, cingulate and rostral
agranular portions. In addition, discrete groups of Drd4-EGFP labelled neurons were observed in the anterior olfactory nucleus,
ventral pallidum, and lateral parabrachial nucleus. EGFP was not detected in the striatum, hippocampus or midbrain as described
using other techniques. Given the fine specificity of EGFP expression in BAC transgenic mice and the high sensitivity of the EGFP
antibody used in this study, our results indicate that Drd4 expression in the adult mouse brain is limited to a more restricted number of
areas than previously reported. Its leading expression in the prefrontal cortex supports the importance of the D4R in complex
behaviours depending on cortical dopamine (DA) transmission and its possible role in the etiopathophysiology of ADHD.Drd4). Immunohistochemical
analysis performed in brain sections of Drd4-EGFP transgenic mice using an anti-EGFP polyclonal antibody showed that transgenic
expression was predominant in deep layer neurons of the prefrontal cortex, particularly in the orbital, prelimbic, cingulate and rostral
agranular portions. In addition, discrete groups of Drd4-EGFP labelled neurons were observed in the anterior olfactory nucleus,
ventral pallidum, and lateral parabrachial nucleus. EGFP was not detected in the striatum, hippocampus or midbrain as described
using other techniques. Given the fine specificity of EGFP expression in BAC transgenic mice and the high sensitivity of the EGFP
antibody used in this study, our results indicate that Drd4 expression in the adult mouse brain is limited to a more restricted number of
areas than previously reported. Its leading expression in the prefrontal cortex supports the importance of the D4R in complex
behaviours depending on cortical dopamine (DA) transmission and its possible role in the etiopathophysiology of ADHD.Drd4-EGFP transgenic mice using an anti-EGFP polyclonal antibody showed that transgenic
expression was predominant in deep layer neurons of the prefrontal cortex, particularly in the orbital, prelimbic, cingulate and rostral
agranular portions. In addition, discrete groups of Drd4-EGFP labelled neurons were observed in the anterior olfactory nucleus,
ventral pallidum, and lateral parabrachial nucleus. EGFP was not detected in the striatum, hippocampus or midbrain as described
using other techniques. Given the fine specificity of EGFP expression in BAC transgenic mice and the high sensitivity of the EGFP
antibody used in this study, our results indicate that Drd4 expression in the adult mouse brain is limited to a more restricted number of
areas than previously reported. Its leading expression in the prefrontal cortex supports the importance of the D4R in complex
behaviours depending on cortical dopamine (DA) transmission and its possible role in the etiopathophysiology of ADHD.Drd4-EGFP labelled neurons were observed in the anterior olfactory nucleus,
ventral pallidum, and lateral parabrachial nucleus. EGFP was not detected in the striatum, hippocampus or midbrain as described
using other techniques. Given the fine specificity of EGFP expression in BAC transgenic mice and the high sensitivity of the EGFP
antibody used in this study, our results indicate that Drd4 expression in the adult mouse brain is limited to a more restricted number of
areas than previously reported. Its leading expression in the prefrontal cortex supports the importance of the D4R in complex
behaviours depending on cortical dopamine (DA) transmission and its possible role in the etiopathophysiology of ADHD.Drd4 expression in the adult mouse brain is limited to a more restricted number of
areas than previously reported. Its leading expression in the prefrontal cortex supports the importance of the D4R in complex
behaviours depending on cortical dopamine (DA) transmission and its possible role in the etiopathophysiology of ADHD.