Expression of brain-derived neurotrophic factor in cortical neurons is regulated by striatal target area.
Changes in BDNF expression after different types of brain insults are related to neuroprotection, stimulation of sprouting, and synaptic reorganization. In the cerebral cortex, an autocrine-paracrine mechanism for BDNF has been proposed because the distribution patterns of BDNF and TrkB expression are almost identical. Moreover, cortical BDNF is anterogradely transported to the striatum, suggesting a role of BDNF in the functional interaction between the two brain regions. Here we have examined the expression of this neurotrophin in the cerebral cortex after various striatal lesions. Intrastriatal injection of quinolinate, kainate, 3-nitropropionic acid, or colchicine increased BDNF mRNA levels in cerebral cortex. In contrast, stimulation of neuronal activity in the striatum did not change cortical BDNF expression. Both excitatory amino acids increased BDNF expression in neurons of cortical layers II/III, V, and VI that project to the striatum. Moreover, grafting a BDNF-secreting cell line prevented both the loss of striatal neurons and the cortical upregulation of BDNF induced by excitotoxins. Because retrograde transport in the corticostriatal pathway was intact after striatal lesions, our results suggest that striatal damage upregulates endogenous BDNF in corticostriatal neurons by a transneuronal mechanism, which may constitute a protective mechanism for striatal and/or cortical cells.
Canals
J M
JM
Departament de Biologia Cel.lular i Anatomia Patològica, Facultat de Medicina, Universitat de Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Casanova 143, E-08036 Barcelona, Spain.
Checa
N
N
Marco
S
S
Akerud
P
P
Michels
A
A
Pérez-Navarro
E
E
Tolosa
E
E
Arenas
E
E
Alberch
J
J
D016475:3T3 Cells; D000818:Animals; D001370:Axonal Transport / Q000187:drug effects; D019208:Brain-Derived Neurotrophic Factor / Q000008:administration & dosage / Q000096:biosynthesis* / Q000235:genetics; D002540:Cerebral Cortex / Q000378:metabolism* / Q000473:pathology; D003078:Colchicine / Q000008:administration & dosage; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism / Q000637:transplantation; D005456:Fluorescent Dyes; D006624:Hippocampus / Q000378:metabolism; D006816:Huntington Disease / Q000378:metabolism* / Q000473:pathology; D017403:In Situ Hybridization; D007608:Kainic Acid / Q000008:administration & dosage; D008297:Male; D051379:Mice; D008845:Microinjections; D009434:Neural Pathways / Q000378:metabolism; D009474:Neurons / Q000378:metabolism*; D009574:Nitro Compounds; D011422:Propionates / Q000008:administration & dosage; D017378:Quinolinic Acid / Q000008:administration & dosage; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D017207:Rats, Sprague-Dawley; D013266:Stilbamidines; D015854:Up-Regulation
C049774:2-hydroxy-4,4'-diamidinostilbene, methanesulfonate salt; D019208:Brain-Derived Neurotrophic Factor; D005456:Fluorescent Dyes; D009574:Nitro Compounds; D011422:Propionates; D012333:RNA, Messenger; D013266:Stilbamidines; D017378:Quinolinic Acid; C015392:3-nitropropionic acid; D007608:Kainic Acid; D003078:Colchicine