Co-localization of brain-derived neurotrophic factor (BDNF) and wild-type huntingtin in normal and quinolinic acid-lesioned rat brain.
Loss of huntingtin-mediated brain-derived neurotrophic factor (BDNF) gene transcription has been described in Huntington's disease (HD) [Zuccato et al. (2001) Science, 293, 493-498]. It has been shown that BDNF is synthesized in the pyramidal layer of cerebral cortex and released in the striatum [Altar et al. (1997) Nature, 389, 856-860; Conner et al. (1997) J. Neurosci., 17, 2295-2313]. Here we show the cellular localization of BDNF in huntingtin-containing neurons in normal rat brain; our double-label immunofluorescence study shows that huntingtin and BDNF are co-contained in approximately 99% of pyramidal neurons of motor cortex. In the striatum, huntingtin is expressed in 75% of neurons containing BDNF. In normal striatum we also show that BDNF is contained in cholinergic and in NOS-containing interneurons, which are relatively resistant to HD degeneration. Furthermore, we show a reduction in huntingtin and in BDNF immunoreactivity in cortical neurons after striatal excitotoxic lesion. Our data are confirmed by an ELISA study of BDNF and by a Western blot analysis of huntingtin in cortex of quinolic acid (QUIN)-lesioned hemispheres. In the lesioned striatum we describe that the striatal subpopulation of cholinergic neurons, surviving degeneration, contain BDNF. The finding that BDNF is contained in nearly all neurons that contain huntingtin in the normal cortex, along with the reduced expression of BDNF after QUIN injection of the striatum, shows that huntingtin may be required for BDNF production in cortex.
Fusco
Francesca R
FR
Basal Ganglia Unit, Laboratory of Experimental Neurorehabilitation, Santa Lucia Foundation IRCCS, Via Ardeatina 306, Rome 00179, Italy. f.fusco@hsantalucia.it
Zuccato
Chiara
C
Tartari
Marzia
M
Martorana
Alessandro
A
De March
Zena
Z
Giampà
Carmela
C
Cattaneo
Elena
E
Bernardi
Giorgio
G
D000818:Animals; D015153:Blotting, Western; D001930:Brain Injuries / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D002135:Calcium-Binding Proteins / Q000378:metabolism; D002452:Cell Count; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D003342:Corpus Striatum / Q000166:cytology / Q000293:injuries / Q000378:metabolism; D004195:Disease Models, Animal; D051937:Dopamine and cAMP-Regulated Phosphoprotein 32; D004797:Enzyme-Linked Immunosorbent Assay; D007839:Functional Laterality; D006801:Humans; D000071058:Huntingtin Protein; D006816:Huntington Disease / Q000378:metabolism / Q000473:pathology; D007150:Immunohistochemistry; D008297:Male; D018613:Microscopy, Confocal / Q000295:instrumentation / Q000379:methods; D009044:Motor Cortex / Q000166:cytology / Q000293:injuries / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism*; D010750:Phosphoproteins / Q000378:metabolism; D017378:Quinolinic Acid; D051381:Rats; D017208:Rats, Wistar
D019208:Brain-Derived Neurotrophic Factor; D002135:Calcium-Binding Proteins; D051937:Dopamine and cAMP-Regulated Phosphoprotein 32; C086055:HTT protein, human; C499524:Htt protein, rat; D000071058:Huntingtin Protein; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D010750:Phosphoproteins; D019001:Nitric Oxide Synthase; D002795:Choline O-Acetyltransferase; D017378:Quinolinic Acid