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Noradrenergic-dopaminergic interactions due to DSP-4-MPTP neurotoxin treatments: Iron connection

Artikel i vetenskaplig tidskrift
Författare Trevor Archer
Publicerad i Current Topics in Behavioral Neurosciences
Volym 29
Sidor 73-86
ISSN 1866-3370
Publiceringsår 2016
Publicerad vid Psykologiska institutionen
Sidor 73-86
Språk en
Länkar dx.doi.org/10.1007/7854_2015_411
Ämnesord Biomarkers, Deficits, DSP-4, Function, Iron overload, Mice, MPTP, NA-DA denervations
Ämneskategorier Neurovetenskaper, Neurologi

Sammanfattning

The investigations of noradrenergic lesions and dopaminergic lesions have established particular profiles of functional deficits and accompanying alterations of biomarkers in brain regions and circuits. In the present account, the focus of these lesions is directed toward the effects upon dopaminergic neurotransmission and expression that are associated with the movement disorders and psychosis-like behavior. In this context, it was established that noradrenergic denervation, through administration of the selective noradrenaline (NA) neurotoxin, DSP-4, should be performed prior to the depletion of dopamine (DA) with the selective neurotoxin, MPTP. Employing this regime, it was shown that (i) following DSP-4 (50 mg/kg) pretreatment of C57/Bl6 mice, both the functional and neurochemical (DA loss) effects of MPTP (2 × 20 and 2 × 40 mg/kg) were markedly exacerbated, and (ii) following postnatal iron (Fe2+, 7.5 mg/kg, on postnatal days 19-12), pretreatment with DSP-4 followed by the lower 2 × 20 mg/kg MPTP dose induced even greater losses of motor behavior and striatal DA. As yet, the combination of NA-DA depletions, and even more so Fe2+-NA-DA depletion, has been considered to present a movement disorder aspect although studies exploring cognitive domains are lacking. With intrusion of iron overload into this formula, the likelihood of neuropsychiatric disorder, as well, unfolds. © Springer International Publishing Switzerland 2015.

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