RGD Reference Report - Cortical neurons from intrauterine growth retardation rats exhibit lower response to neurotrophin BDNF. - Rat Genome Database

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Cortical neurons from intrauterine growth retardation rats exhibit lower response to neurotrophin BDNF.

Authors: Ninomiya, M  Numakawa, T  Adachi, N  Furuta, M  Chiba, S  Richards, M  Shibata, S  Kunugi, H 
Citation: Ninomiya M, etal., Neurosci Lett. 2010 May 31;476(2):104-9. Epub 2010 Apr 14.
RGD ID: 4107070
Pubmed: PMID:20398734   (View Abstract at PubMed)
DOI: DOI:10.1016/j.neulet.2010.03.082   (Journal Full-text)

Intrauterine growth retardation (IUGR) is putatively involved in the pathophysiology of schizophrenia. The animal model of IUGR induced by synthetic thromboxane A2 (TXA2) is useful to clarify the effect of IUGR on pups' brains, however, analysis at the cellular level is still needed. Brain-derived neurotrophic factor (BDNF), which plays a role in neuronal survival and synaptic plasticity in the central nervous system (CNS), may also be associated with schizophrenia. However, the possible relationship between IUGR and BDNF function remains unclear. Here, we examined how IUGR by TXA2 impacts BDNF function by using dissociated cortical neurons. We found that, although BDNF levels in cultured neurons from the cerebral cortex of low birth weight pups with IUGR were unchanged, TrkB (BDNF receptor) was decreased compared with control-rats. BDNF-stimulated MAPK/ERK1/2 and PI3K/Akt pathways, which are downstream intracellular signaling pathways of TrkB, were repressed in IUGR-rat cultures. Expression of glutamate receptors such as GluA1 and GluN2A was also suppressed in IUGR-rat cultures. Furthermore, in IUGR-rat cultures, anti-apoptotic protein Bcl2 was decreased and BDNF failed to prevent neurons from cell death caused by serum-deprivation. Taken together, IUGR resulted in reductions in cell viability and in synaptic function following TrkB down-regulation, which may play a role in schizophrenia-like behaviors.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Fetal Growth Retardation  ISOGria1 (Rattus norvegicus)4107070; 4107070protein:decreased expression:cerebral cortical neuron (rat)RGD 
Fetal Growth Retardation  ISOGrin2a (Rattus norvegicus)4107070; 4107070protein:decreased expression:cerebral cortical neuron (rat)RGD 
Fetal Growth Retardation  IEP 4107070; 4107070protein:decreased expression:cerebral cortical neuron (rat)RGD 

Objects Annotated

Genes (Rattus norvegicus)
Gria1  (glutamate ionotropic receptor AMPA type subunit 1)
Grin2a  (glutamate ionotropic receptor NMDA type subunit 2A)

Genes (Mus musculus)
Gria1  (glutamate receptor, ionotropic, AMPA1 (alpha 1))
Grin2a  (glutamate receptor, ionotropic, NMDA2A (epsilon 1))

Genes (Homo sapiens)
GRIA1  (glutamate ionotropic receptor AMPA type subunit 1)
GRIN2A  (glutamate ionotropic receptor NMDA type subunit 2A)


Additional Information