Chronic supranigral infusion of BDNF in normal and MPTP-treated common marmosets.

Abstract

BDNF or vehicle were administered by unilateral supranigral infusion in normal and chronically lesioned MPTP-treated common marmosets (Callithrix jacchus) for four weeks and locomotor activity, disability and response to apomorphine were assessed with nigral TH, GFAP and GAD immunoreactivity and striatal [3H]mazindol autoradiography. Selective contraversive orientation and ipsilateral neglect evolved in MPTP-treated marmosets receiving BDNF with no significant difference in disability or locomotor activity when compared to the vehicle-infused group. Apomorphine produced an ipsiversive rotational bias in BDNF-treated animals. In normal animals infused with BDNF contralateral neglect, ipsiversive turning, postural instability and ataxia rapidly evolved. In MPTP-treated marmosets BDNF caused increased ipsilateral striatal [3H]mazindol binding with increased somatic size and staining intensity in GAD-immunoreactive cells and a 10-20% loss of nigral TH-immunoreactive cells with increased GFAP staining. In normal common marmosets, both vehicle and BDNF infusion decreased nigral TH-immunoreactivity. Chronic supranigral infusion of BDNF alters motor behaviour and spatial attention in MPTP-treated marmosets which may reflect altered function in residual nigral dopaminergic neurons and brainstem GABAergic neurons and in normal animals produces behavioural and histological signs of nigrostriatal hypofunction.