PMID- 16963163
OWN - NLM
STAT- MEDLINE
DCOM- 20070320
LR  - 20091119
IS  - 0197-0186 (Print)
IS  - 0197-0186 (Linking)
VI  - 50
IP  - 1
DP  - 2007 Jan
TI  - CCK-8 induces NGF and BDNF synthesis and modulates TrkA and TrkB expression in 
      the rat hippocampus and septum: Effects on kindling development.
PG  - 130-8
AB  - In our previous studies, we demonstrated that intraperitoneal (i.p.) injections 
      with the neurotransmitter/neuromodulatory peptide Cholecystokinin-8 (CCK-8) 
      stimulate the synthesis of the neurotrophin nerve growth factor (NGF) resulting 
      in the structural and functional recovery of neuronal damage. This 
      neurotrophin-mediated neuroprotective action of CCK-8 has opened a new 
      perspective for a better understanding of the CCK neurobiological and 
      pharmacological properties. To explore the possible beneficial effects of the 
      CCK-induced increase of neurotrophin availability in brain, we compared the 
      effects of i.p. CCK-8 in healthy rats and in a chemical kindling model using a 
      subconvulsive dose of pentylenetetrazol (PTZ). Behavioural changes were monitored 
      during treatment and classified according to a six-point scale. After 3 weeks of 
      treatment (12 trials), the PTZ group of rats manifested generalized clonic-tonic 
      seizures (Class 5 behaviour). For this reason, this time point was chosen to 
      compare the effects of CCK-8 treatment on the expression of NGF, the brain 
      derived neurotrophin factor (BDNF) and their receptors in the septum and 
      hippocampus. We found that repeated i.p. injections with CCK-8 in adult rats 
      result in: (1) an increase of NGF and BDNF protein and mRNA levels in the septum 
      and hippocampus; (2) a down-regulation of TrkA and p75NTR and an up-regulation of 
      TrkB; (3) reduced susceptibility to develop chemical kindling; (4) recovery of 
      the PTZ-induced changes in the expression of neurotrophin receptors in the septal 
      and hippocampal tissues. This data clearly indicates that CCK-induced variation 
      of neurotrophin synthesis in brain is able to influence the susceptibility to 
      develop seizures in adult rats most probably by counteracting the progressive 
      neuronal dysfunction and/or damage.
FAU - Tirassa, Paola
AU  - Tirassa P
AD  - Institute of Neurobiology and Molecular Medicine (CNR), Italy. 
      paola.tirassa@inmm.cnr.it
FAU - Costa, Nicola
AU  - Costa N
LA  - eng
PT  - Journal Article
DEP - 20060911
PL  - England
TA  - Neurochem Int
JT  - Neurochemistry international
JID - 8006959
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (DNA Primers)
RN  - 0 (Peptide Fragments)
RN  - 0 (cholecystokinin 8)
RN  - 9011-97-6 (Cholecystokinin)
RN  - 9061-61-4 (Nerve Growth Factor)
RN  - EC 2.7.10.1 (Receptor, trkA)
RN  - EC 2.7.10.1 (Receptor, trkB)
SB  - IM
MH  - Animals
MH  - Base Sequence
MH  - Behavior, Animal/drug effects
MH  - Brain-Derived Neurotrophic Factor/*biosynthesis
MH  - Cholecystokinin/*pharmacology
MH  - DNA Primers
MH  - Hippocampus/*drug effects/metabolism/physiology
MH  - *Kindling, Neurologic
MH  - Male
MH  - Nerve Growth Factor/*biosynthesis
MH  - Peptide Fragments/*pharmacology
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptor, trkA/*metabolism
MH  - Receptor, trkB/*metabolism
EDAT- 2006/09/12 09:00
MHDA- 2007/03/21 09:00
CRDT- 2006/09/12 09:00
PHST- 2006/02/09 00:00 [received]
PHST- 2006/07/11 00:00 [revised]
PHST- 2006/07/14 00:00 [accepted]
PHST- 2006/09/12 09:00 [pubmed]
PHST- 2007/03/21 09:00 [medline]
PHST- 2006/09/12 09:00 [entrez]
AID - S0197-0186(06)00248-8 [pii]
AID - 10.1016/j.neuint.2006.07.008 [doi]
PST - ppublish
SO  - Neurochem Int. 2007 Jan;50(1):130-8. doi: 10.1016/j.neuint.2006.07.008. Epub 2006 
      Sep 11.