BDNF controls dopamine D3 receptor expression and triggers behavioural sensitization
Identifieur interne : 001090 ( PascalFrancis/Checkpoint ); précédent : 001089; suivant : 001091BDNF controls dopamine D3 receptor expression and triggers behavioural sensitization
Auteurs : Olivier Guillin [France] ; Jorge Diaz [France] ; Patrick Carroll [France] ; Nathalie Griffon [France] ; Jean-Charles Schwartz [France] ; Pierre Sokoloff [France]Source :
- Nature : (London) [ 0028-0836 ] ; 2001.
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Abstract
Brain-derived neurotrophic factor (BDNF), like other neurotrophins, is a polypeptidic factor initially regarded to be responsible for neuron proliferation, differentiation and survival, through its uptake at nerve terminals and retrograde transport to the cell body1. A more diverse role for BDNF has emerged progressively from observations showing that it is also transported anterogradely2,3, is released on neuron depolarization1, and triggers rapid intracellular signals4 and action potentials in central neurons5. Here we report that BDNF elicits long-term neuronal adaptations by controlling the responsiveness of its target neurons to the important neurotransmitter, dopamine. Using lesions and gene-targeted mice lacking BDNF, we show that BDNF from dopamine neurons is responsible for inducing normal expression of the dopamine D3 receptor in nucleus accumbens6-8 both during development and in adulthood. BDNF from corticostriatal neurons3also induces behavioural sensitization, by triggering overexpression of the D3 receptor in striatum of hemiparkinsonian rats9. Our results suggest that BDNF may be an important determinant of pathophysiological conditions such as drug addiction10, schizophrenia" or Parkinson's disease12, in which D3 receptor expression is abnormal.
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<front><div type="abstract" xml:lang="en">Brain-derived neurotrophic factor (BDNF), like other neurotrophins, is a polypeptidic factor initially regarded to be responsible for neuron proliferation, differentiation and survival, through its uptake at nerve terminals and retrograde transport to the cell body<sup>1</sup>
. A more diverse role for BDNF has emerged progressively from observations showing that it is also transported anterogradely<sup>2,3</sup>
, is released on neuron depolarization<sup>1</sup>
, and triggers rapid intracellular signals<sup>4</sup>
and action potentials in central neurons<sup>5</sup>
. Here we report that BDNF elicits long-term neuronal adaptations by controlling the responsiveness of its target neurons to the important neurotransmitter, dopamine. Using lesions and gene-targeted mice lacking BDNF, we show that BDNF from dopamine neurons is responsible for inducing normal expression of the dopamine D<sub>3</sub>
receptor in nucleus accumbens<sup>6-8</sup>
both during development and in adulthood. BDNF from corticostriatal neurons<sup>3</sup>
also induces behavioural sensitization, by triggering overexpression of the D<sub>3</sub>
receptor in striatum of hemiparkinsonian rats<sup>9</sup>
. Our results suggest that BDNF may be an important determinant of pathophysiological conditions such as drug addiction<sup>10</sup>
, schizophrenia" or Parkinson's disease<sup>12</sup>
, in which D<sub>3</sub>
receptor expression is abnormal.</div>
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. A more diverse role for BDNF has emerged progressively from observations showing that it is also transported anterogradely<sup>2,3</sup>
, is released on neuron depolarization<sup>1</sup>
, and triggers rapid intracellular signals<sup>4</sup>
and action potentials in central neurons<sup>5</sup>
. Here we report that BDNF elicits long-term neuronal adaptations by controlling the responsiveness of its target neurons to the important neurotransmitter, dopamine. Using lesions and gene-targeted mice lacking BDNF, we show that BDNF from dopamine neurons is responsible for inducing normal expression of the dopamine D<sub>3</sub>
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<s5>29</s5>
</fC07>
<fC07 i1="02" i2="X" l="SPA"><s0>Factor neurotrófico</s0>
<s5>29</s5>
</fC07>
<fC07 i1="03" i2="X" l="FRE"><s0>Rodentia</s0>
<s2>NS</s2>
</fC07>
<fC07 i1="03" i2="X" l="ENG"><s0>Rodentia</s0>
<s2>NS</s2>
</fC07>
<fC07 i1="03" i2="X" l="SPA"><s0>Rodentia</s0>
<s2>NS</s2>
</fC07>
<fC07 i1="04" i2="X" l="FRE"><s0>Mammalia</s0>
<s2>NS</s2>
</fC07>
<fC07 i1="04" i2="X" l="ENG"><s0>Mammalia</s0>
<s2>NS</s2>
</fC07>
<fC07 i1="04" i2="X" l="SPA"><s0>Mammalia</s0>
<s2>NS</s2>
</fC07>
<fC07 i1="05" i2="X" l="FRE"><s0>Vertebrata</s0>
<s2>NS</s2>
</fC07>
<fC07 i1="05" i2="X" l="ENG"><s0>Vertebrata</s0>
<s2>NS</s2>
</fC07>
<fC07 i1="05" i2="X" l="SPA"><s0>Vertebrata</s0>
<s2>NS</s2>
</fC07>
<fN21><s1>190</s1>
</fN21>
</pA>
</standard>
</inist>
<affiliations><list><country><li>France</li>
</country>
<region><li>Provence-Alpes-Côte d'Azur</li>
<li>Île-de-France</li>
</region>
<settlement><li>Marseille</li>
<li>Paris</li>
</settlement>
</list>
<tree><country name="France"><region name="Île-de-France"><name sortKey="Guillin, Olivier" sort="Guillin, Olivier" uniqKey="Guillin O" first="Olivier" last="Guillin">Olivier Guillin</name>
</region>
<name sortKey="Carroll, Patrick" sort="Carroll, Patrick" uniqKey="Carroll P" first="Patrick" last="Carroll">Patrick Carroll</name>
<name sortKey="Diaz, Jorge" sort="Diaz, Jorge" uniqKey="Diaz J" first="Jorge" last="Diaz">Jorge Diaz</name>
<name sortKey="Griffon, Nathalie" sort="Griffon, Nathalie" uniqKey="Griffon N" first="Nathalie" last="Griffon">Nathalie Griffon</name>
<name sortKey="Schwartz, Jean Charles" sort="Schwartz, Jean Charles" uniqKey="Schwartz J" first="Jean-Charles" last="Schwartz">Jean-Charles Schwartz</name>
<name sortKey="Schwartz, Jean Charles" sort="Schwartz, Jean Charles" uniqKey="Schwartz J" first="Jean-Charles" last="Schwartz">Jean-Charles Schwartz</name>
<name sortKey="Sokoloff, Pierre" sort="Sokoloff, Pierre" uniqKey="Sokoloff P" first="Pierre" last="Sokoloff">Pierre Sokoloff</name>
</country>
</tree>
</affiliations>
</record>
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