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Changes Of Peripheral-type Benzodiazepine Receptor (PBR) In The Brain Mitochodria Of Aging Rats And Its Response To Anesthesia Induction Agent Atropine

Posted on:2011-02-10Degree:MasterType:Thesis
Country:ChinaCandidate:Y ZhaoFull Text:PDF
GTID:2144360305467776Subject:Pharmacology
Abstract/Summary:PDF Full Text Request
The incidence of post-operative mental disorders (POMD) related to anaesthesia increases in elderly patients, which are characterized by post-operative delirium, cognitive impairment, anxiety and depression, and influence post-operative rehabilitation and threaten to life in some cases. The pathophysiology of POMD is poorly understood. Good evidence suggests neurotransmitter disturbances, especially acetylcholine deficiency. In the present study, the effect of anticholinergic agent—atropine which was used in the course of anesthesia induction on psychiatric symptoms and memory were evaluated in aging rats. Our data of morris water maze and Y maze showed the cognition of aging rats was impaired and atropine at clinical dose had no obvious effect on it.. However, atropine had a certain impact on psychiatric symptoms, which was showed in open field and elevated plus maze test. To confirm the precise mechanism of atropine, the quantitive changes of peripheral-type benzodiazepine recepors (PBRs) in brain mitochodria of aging rats and the effect of atropine on it were examined. Our findings showed that compared with 3-month rats, there was an increase in the maximal binding site density (Bmax), with an significant increase in the equilibrium dissociation constant (Kd) in cortex mitochondria of aging rats, which suggested the density of PBRs increased, whereas the binding affinity of PBRs decreased. On 1 st day after atropine treatment, the density of PBRs showed further enhancement but the binding affinity of PBRs further decreased. Meanwhile, we found that compared with 3-month rats, the transcriptional level and the protein level of the three proteins—P450scc,StAR and 3β-HSD which related to the neurosteroids'biosynthesis in the brain decreased. On 4th day after atropine treatment, the transcriptional levels of P450scc and 3β-HSD were significantly lower than those in the control aging rats. However, their levels were restored on 7th day. The changes of the protein level lagged behind the mRNA, and the protein expression decreased in a time-coursing pattern.In conclusion, in this study, the decrease of the basal level of aged rats cognition, the binding activity of PBRs in brain mitochodria of aging rats and the expression of the proteins regard to neurosteroids de novo synthesis were observed, which maybe related to the susceptibility of old age to POMD. Anesthesia induction agents-atropine had no significant effect on memory function, but exerted some effect on psychiatric symptoms, implicating the influence of the combination of anticholinergic agents and anesthetics on POMD in old patients need to be further investigated.
Keywords/Search Tags:aging, anticholinergic agents, atropine, peripheral-type benzodiazepine recepors (PBRs), post-operative mental disorders (POMD)
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