Chronic supranigral infusion of BDNF in normal and MPTP-treated common marmosets.
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.
Pearce
R K
RK
Neurodegenerative Diseases Research Centre, Biomedical Sciences Division, King's College London, and The National Hospital for Neurology, United Kingdom.
Costa
S
S
Jenner
P
P
Marsden
C D
CD
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000494:pharmacology / Q000627:therapeutic use*; D002144:Callithrix; D015259:Dopamine Agents; D018765:Dopamine Uptake Inhibitors / Q000378:metabolism; D005968:Glutamate Decarboxylase / Q000378:metabolism; D008454:Mazindol / Q000378:metabolism; D009043:Motor Activity / Q000187:drug effects* / Q000502:physiology; D020734:Parkinsonian Disorders / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D020955:Striatonigral Degeneration / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D013378:Substantia Nigra / Q000187:drug effects / Q000293:injuries / Q000378:metabolism*; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D019208:Brain-Derived Neurotrophic Factor; D015259:Dopamine Agents; D018765:Dopamine Uptake Inhibitors; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D008454:Mazindol; D014446:Tyrosine 3-Monooxygenase; D005968:Glutamate Decarboxylase