RGD Reference Report - Amantadine alleviates postoperative cognitive dysfunction possibly by increasing glial cell line-derived neurotrophic factor in rats. - Rat Genome Database

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Amantadine alleviates postoperative cognitive dysfunction possibly by increasing glial cell line-derived neurotrophic factor in rats.

Authors: Zhang, Junfeng  Tan, Hongying  Jiang, Wei  Zuo, Zhiyi 
Citation: Zhang J, etal., Anesthesiology. 2014 Oct;121(4):773-85. doi: 10.1097/ALN.0000000000000352.
RGD ID: 405849389
Pubmed: PMID:25251457   (View Abstract at PubMed)
PMCID: PMC4176814   (View Article at PubMed Central)
DOI: DOI:10.1097/ALN.0000000000000352   (Journal Full-text)


BACKGROUND: Postoperative cognitive dysfunction is a clinical entity that is associated with poor outcome. We determined the effectiveness of amantadine in reducing surgery-induced cognitive impairment and the role of glial cell line-derived neurotrophic factor (GDNF) in this effect.
METHODS: Four-month old male Fischer 344 rats were subjected to right carotid exposure under intravenous anesthesia. Some rats received intraperitoneal injection of 25 mg/kg/day amantadine for 3 days with the first dose at 15 min before the surgery or intracerebroventricular injection of GDNF or an anti-GDNF antibody at the end of surgery. One week later, rats were started to be tested by Barnes maze and fear conditioning. Hippocampus was harvested at 6 h, 24 h or 10 days after the surgery for biochemical analysis. C8-B4 cells, a microglial cell line, were pretreated with 1 ng/ml GDNF for 30 min before being exposed to 5 ng/ml lipopolysaccharide for 2 h.
RESULTS: Surgery increased the time to identify the target box in the Barnes maze when tested 1 day [22 (median) (11-66) (interquartile range) of control group vs. 158 (29-180) of surgery group, n = 15, P = 0.022) or 8 days after the training sessions and reduced context-related freezing behavior in the fear conditioning test. These effects were attenuated by amantadine (25 (14-90), n = 15, P = 0.029 compared with surgery group at 1 day after the training sessions in Barnes maze) and intracerebroventricular GDNF. Amantadine increased GDNF that was co-localized with glial fibrillary acidic protein, an astrocytic marker, in the hippocampus. Intracerebroventricular injection of an anti-GDNF antibody but not the denatured antibody blocked the effects of amantadine on cognition. Surgery induced neuroinflammation that was inhibited by amantadine. Lipopolysaccharide increased interleukin 1β production from C8-B4 cells. This effect was inhibited by GDNF.
CONCLUSIONS: Our results suggest that amantadine attenuated surgery-induced learning and memory impairment. This effect may be mediated by GDNF via inhibition of neuroinflammation.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
GDNFHumanPostoperative Cognitive Dysfunction treatmentISOGdnf (Rattus norvegicus) RGD 
GdnfRatPostoperative Cognitive Dysfunction treatmentIDA  RGD 
GdnfMousePostoperative Cognitive Dysfunction treatmentISOGdnf (Rattus norvegicus) RGD 

Objects Annotated

Genes (Rattus norvegicus)
Gdnf  (glial cell derived neurotrophic factor)

Genes (Mus musculus)
Gdnf  (glial cell line derived neurotrophic factor)

Genes (Homo sapiens)
GDNF  (glial cell derived neurotrophic factor)


Additional Information