PMID- 10619567
OWN - NLM
STAT- MEDLINE
DCOM- 20000114
LR  - 20131121
IS  - 0014-4886 (Print)
IS  - 0014-4886 (Linking)
VI  - 160
IP  - 2
DP  - 1999 Dec
TI  - Alterations in nigrostriatal dopaminergic function within BDNF mutant mice.
PG  - 500-7
AB  - The influence of brain-derived neurotrophic factor (BDNF) upon the nigrostriatal 
      dopaminergic system was evaluated in weanling and adult mice carrying a targeted 
      inactivated BDNF gene. Regional specificity of this BDNF mutation was assessed by 
      assaying catecholamine concentrations within the corpus striatum, hypothalamus, 
      and olfactory bulbs. In weanling mice dopamine, but not norepinephrine, 
      concentrations within the corpus striatum of homozygous mutant (-/-) mice were 
      significantly reduced with levels being 54% that of the wild-type controls (+/+) 
      and 49% that of the heterozygous mutant (+/-) mice. While no differences were 
      obtained among the three genotypes for hypothalamic dopamine, norepinephrine 
      concentrations of -/- mice were significantly lower, being 62% of +/+ mice and 
      49% of +/- mice. The dopamine concentrations of -/- mice within the olfactory 
      bulb were significantly reduced (69%) compared to the +/-, but not +/+ mice. 
      Olfactory bulb norepinephrine concentrations showed a statistically significant 
      difference among each of the three conditions with minimal levels in -/- mice 
      (62% of +/+ and 45% of +/-). In the adults, catecholamine concentrations were 
      measured only in +/+ and +/- mice since -/- mice do not typically survive past 21 
      days. Dopamine, but not norepinephrine, concentrations within the corpus striatum 
      were significantly increased (116%) in +/- compared to +/+ mice. No other 
      statistically significant differences were obtained in catecholamine 
      concentrations within the hypothalamus or olfactory bulb in these adult mice. 
      These results show that homozygous BDNF mutations produce severe depletions 
      within the nigrostriatal dopaminergic system and substantial reductions of 
      norepinephrine within the hypothalamus and olfactory bulb. Interestingly, maximal 
      catecholamine concentrations for all areas sampled at both ages were observed in 
      the +/- mice. These latter findings may indicate some subtle changes in 
      catecholamine functions resulting from a heterozygous BDNF mutation.
FAU - Dluzen, D E
AU  - Dluzen DE
AD  - Department of Anatomy, Northeastern Ohio Universities College of Medicine, 
      Roostown 44272-0095, USA.
FAU - Story, G M
AU  - Story GM
FAU - Xu, K
AU  - Xu K
FAU - Kucera, J
AU  - Kucera J
FAU - Walro, J M
AU  - Walro JM
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PL  - United States
TA  - Exp Neurol
JT  - Experimental neurology
JID - 0370712
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - VTD58H1Z2X (Dopamine)
RN  - X4W3ENH1CV (Norepinephrine)
SB  - IM
EIN - Exp Neurol 2002 Nov;178(1):147
MH  - Animals
MH  - Brain-Derived Neurotrophic Factor/deficiency/genetics/*physiology
MH  - Corpus Striatum/*metabolism
MH  - Dopamine/*metabolism
MH  - Heterozygote
MH  - Hypothalamus/*metabolism
MH  - Mice
MH  - Mice, Knockout
MH  - Norepinephrine/metabolism
MH  - Olfactory Bulb/metabolism
MH  - Polymerase Chain Reaction
MH  - Reference Values
MH  - Substantia Nigra/*metabolism
EDAT- 2000/01/05 00:00
MHDA- 2000/01/05 00:01
CRDT- 2000/01/05 00:00
PHST- 2000/01/05 00:00 [pubmed]
PHST- 2000/01/05 00:01 [medline]
PHST- 2000/01/05 00:00 [entrez]
AID - S0014-4886(99)97225-4 [pii]
AID - 10.1006/exnr.1999.7225 [doi]
PST - ppublish
SO  - Exp Neurol. 1999 Dec;160(2):500-7. doi: 10.1006/exnr.1999.7225.