Altered midbrain dopaminergic neurotransmission during development in an animal model of ADHD.
To understand the onset and the molecular mechanisms triggering dopaminergic (DA) dysregulation in Attention-Deficit Hyperactivity Disorder (ADHD), we have used the Spontaneously Hypertensive Rats (SHR), the most widely studied animal model for this disease. We have studied the pattern of expression of specific genes involved in DA neuron differentiation, survival and function during postnatal (P) development of the ventral midbrain in SHR males. Our results show that tyrosine hydroxylase and DA transporter gene expression are significantly and transiently reduced in the SHR midbrain during the first month of postnatal development, although with a different kinetic. The other genes analyzed do not show significant variation between SHR and control rats. In addition, high-affinity DA uptake activity is significantly reduced in synaptosomes obtained from the striatum of 1-month-old SHR, when compared to controls. Our data suggest that down-regulation of DA neurotransmission occurs in the midbrain of SHR in a developmentally regulated temporal window during postnatal development, thus strengthening the hypodopaminergic hypothesis in the pathogenesis of ADHD.
Leo
Damiana
D
Institute of Genetics and Biophysics 'A Buzzati Traverso', CNR, Via P. Castellino 111, Naples 80135, Italy.
Sorrentino
Eleonora
E
Volpicelli
Floriana
F
Eyman
Maria
M
Greco
Dario
D
Viggiano
Davide
D
di Porzio
Umberto
U
Perrone-Capano
Carla
C
D000818:Animals; D001289:Attention Deficit Disorder with Hyperactivity / Q000235:genetics / Q000503:physiopathology*; D001923:Brain Chemistry / Q000235:genetics; D002454:Cell Differentiation; D004195:Disease Models, Animal; D004298:Dopamine / Q000235:genetics / Q000378:metabolism*; D015536:Down-Regulation; D018507:Gene Expression Regulation, Developmental; D008297:Male; D008636:Mesencephalon / Q000166:cytology / Q000254:growth & development* / Q000378:metabolism*; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D009435:Synaptic Transmission / Q000235:genetics*
D004298:Dopamine