Effects of BDNF and NT-4/5 on striatonigral neuropeptides or nigral GABA neurons in vivo.
Supranigral infusions of the TrkB-receptor-preferring neurotrophins BDNF or NT-4/5 augment locomotor behaviours, pars compacta firing rates and striatal dopamine metabolism. However these actions of BDNF or NT-4/5 may involve other neurotransmitter systems in addition to dopamine neurons in the substantia nigra. We thus investigated the effects of 2-week supranigral infusions of BDNF or NT-4/5 on rat peptidergic striatonigral neurons and nigral GABAergic neurons. Radioimmunoassay revealed that BDNF and NT-4/5 elevated substantia nigra levels of substance P (by 46 and 57% respectively) and substance K (by 64 and 81%). In addition, BDNF elevated substance K by 59% in a nigral projection area, the superior colliculus. NT-4/5 elevated dynorphin A in the substantia nigra (by 52%) and met-enkephalin in substantia nigra and globus pallidus (by 89%). None of these neuropeptides were altered in the striatum. Consistent with these findings, supranigral infusions of BDNF elevated the mRNA for preprotachykinin A in striatal neurons. In the same animals, glutamic acid decarboxylase (GAD)67 mRNA was increased by 48% in the substantia nigra. The cross-sectional area of GAD67-positive neuronal somata in the BDNF-infused nigra was increased by 59%, and 70% of nigral GABAergic neurons had a cross-sectional area > 550 microns2, whereas 95% of the neurons in vehicle-infused animals had cross-sectional areas < 550 microns2. Thus, supranigral infusions of BDNF or NT-4/5 increase tachykinin mRNA and protein levels within striatonigral neurons and increase the size and GAD67 mRNA expression levels of nigral GABAergic neurons. These results suggest that BDNF or NT-4/5 may modify the output of the basal ganglia not only through effects on dopamine neurons but also by increasing neurotransmission in striatonigral peptidergic and nigral GABAergic pathways.
Arenas
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E
Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, Sweden.
Akerud
P
P
Wong
V
V
Boylan
C
C
Persson
H
H
Lindsay
R M
RM
Altar
C A
CA
D000661:Amphetamine / Q000494:pharmacology; D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000494:pharmacology*; D003342:Corpus Striatum / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D007263:Infusions, Parenteral; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D009414:Nerve Growth Factors / Q000494:pharmacology*; D009474:Neurons / Q000737:chemistry / Q000187:drug effects*; D009479:Neuropeptides / Q000378:metabolism*; D011498:Protein Precursors / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D012399:Rotation; D013378:Substantia Nigra / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D015320:Tachykinins / Q000235:genetics; D005680:gamma-Aminobutyric Acid / Q000032:analysis
D019208:Brain-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; D009479:Neuropeptides; D011498:Protein Precursors; D012333:RNA, Messenger; D015320:Tachykinins; C044206:preprotachykinin; D005680:gamma-Aminobutyric Acid; D000661:Amphetamine