FEBS Lett. 2007 Apr
3;581(7):1357-61. Epub
2007 Mar 2. Overexpression of pitx3 upregulates
expression of BDNF and GDNF in SH-SY5Y cells and primary ventral mesencephalic cultures. ·
Peng
C, Fan S, Li X, Fan X, Ming M, Sun Z, Le W. The transcription factor Pitx3 plays an important role
in the development of midbrain to promote the growth and differentiation of
dopamine neurons. The present study has demonstrated that overexpression of Pitx3 in SH-SY5Y cells and primary
ventral mesencephalic (VM) cultures significantly
increased the mRNA levels of brain-derived neurotrophic
factor (BDNF) and glial cell line-derived neurotrophic factor (GDNF), and remarkably elevated the
protein levels of these two neurotrophic factors.
Our data provide the first evidence that pitx3-expressing cells are able to
upregulate the expression of BDNF and GDNF.
Therefore, Pitx3 might be a good target for the treatment of Parkinson's
disease. PMID: 17350004 [PubMed - in
process] Int J Neurosci.
2007 Mar;117(3):315-26. Functional recovery and
expression of GDNF seen in photochemically
induced cerebral infarction. ·
Horinouchi
K, Ikeda S, Harada K, Ohwatashi
A, Kamikawa
Y, Yoshida A,
Nomoto
Y, Etoh
S, Kawahira
K. Department of Rehabilitation and Physical
Medicine, Graduate school of Medical and Dental Sciences, Kagoshima
University, Sakuragaoka, Kagoshima, Japan. Glial cell line-derived neurotrophic factor (GDNF) is a potent neurotrophic factor involved in the survival and
proliferation of neurons. However, there have been few reports examining
the relationship between GDNF and functional recovery after cerebral
infarction. The authors investigated the change in the expression of GDNF
proteins during functional recovery in rats following photochemically
induced cerebral infarctions. Functional recovery for the first 14 days
after the infarction was evaluated using a beam-walking test. The number of
GDNF-like immunoreactive cells around the
infarction were counted at various times (24 h, 72 h, 7 days, and 14 days)
post-infarction. Immunohistochemical analysis of
brain sections showed that the expression of GDNF-like immunoreactive
cells was significantly increased in the temporal cortex until 7 days on
the side ipsilateral to the infarction, and had
decreased by 14 days. Likewise, the functional recovery of paralysis was
substantial until 7 days post-infarction, after which the improvement was
mild. Therefore, the expression of GDNF protein might have some
relationship with the functional recovery of paralysis. There are great
hopes that GDNF could be used as a therapeutic agent for cerebral
infarction. PMID: 17365117 [PubMed - in
process] Exp
Neurol. 2007 Jan 24; [Epub ahead of print] Midbrain expression of
Delta-like 1 homologue is regulated by GDNF and is associated with dopaminergic differentiation. ·
Christophersen
NS, Gronborg
M, Petersen TN,
Fjord-Larsen L,
Jorgensen JR,
Juliusson
B, Blom
N, Rosenblad
C, Brundin
P. Neuronal Survival Unit, Department of
Experimental Medical Science, Wallenberg Neuroscience Center, Lund
University, SE-22184 Lund, Sweden; NsGene A/S, Baltorpvej 154, DK-2750 Ballerup,
Denmark. Affymetrix GeneChip
technology and quantitative real-time PCR (Q-PCR) were used to examine
changes in gene expression in the adult murine substantia nigra pars compacta (SNc) following lentiviral glial cell
line-derived neurotrophic factor (GDNF) delivery
in adult striatum. We identified several genes that were upregulated after GDNF treatment. Among these, the gene
encoding the transmembrane protein Delta-like 1
homologue (Dlk1) was upregulated with a greater
than 4-fold increase in mRNA encoding this protein. Immunohistochemistry
with a Dlk1-specific antibody confirmed the observed upregulation
with increased positive staining of cell bodies in the SNc
and fibers in the striatum. Analysis of the developmental regulation of
Dlk1 in the murine ventral midbrain showed that
the upregulation of Dlk1 mRNA correlated with the
generation of tyrosine hydroxylase (TH)-positive
neurons. Furthermore, Dlk1 expression was analyzed in MesC2.10 cells, which
are derived from embryonic human mesencephalon
and capable of undergoing differentiation into dopaminergic
neurons. We detected upregulation of Dlk1 mRNA
and protein under conditions where MesC2.10 cells differentiate into a dopaminergic phenotype (41.7+/-7.1% Dlk1+ cells). In
contrast, control cultures subjected to default differentiation into non-dopaminergic neurons only expressed very few
(3.7+/-1.3%) Dlk1-immunopositive cells. The
expression of Dlk1 in MesC2.10 cells was specifically upregulated
by the addition of GDNF. Thus, our data suggest that Dlk1 expression
precedes the appearance of TH in mesencephalic
cells and that levels of Dlk1 are regulated by GDNF. PMID: 17320866 [PubMed - as
supplied by publisher]
