The Expression Of GHSR In Hippocampus Of Intrauterine Growth Etardation Rats And Its Relationship With Memory, Learning, Motion And Behavior

Intrauterine growth retardation (IUGR) is that the intra-uterine growth offetus is inhibited which leads to failure of reaching full growth potential.Clinically such fetus all called small for gestational age (SGA). The diagnosticcode for SGA is that the fetus whose birth weight is lower than the tenthpercentile of the average birth weight calculated out of the normal fetus.Maternal and fetal factors such as malnutrition during pregnancy, ischemia offetus and dyscrinism, are supposed to be possible elements causing IUGR.During the process of animal experiment, the target of modeling IUGRanimals is that birth weight of newborns in model group is lower thanx-2sdof that in control group. IUGR can lead to changes in physiology, metabolism,which are closely related to many diseases in adult stage. IUGR is alsosupposed to play a role in the intellectual development and the formation ofcharacter disorder in children. Due to the changes in perinatal-neonatal factors,education factors, nutrition conditions and social environment, researchesconcerning the effects of IUGR on neurobehavioral development of childrenoften results in different outcomes.When suffered malnutrition, illness, lack of necessary hormone，children gradually deviate from their original growth rhythm, which leads todevelopmental retardation. Once the factors mentioned above are removed,children’s growth would accelerate to restore the loss. This phenomenon isdefined as Catch-up growth (CUG). Catch-up growth has already beenobserved in IUGR animal models. Research shows that IUGR has a negativeinfluence on brain development which leads to delay of cognition and learningdysfunction, while catch-up growth could compensate for the problemsmentioned above. Growth Hormone Secretagogues Receptor (GHSR) is a protein that isdiscovered in hypothalamus and other kind of tissue inside human body andsuccessfully cloned in1996. On basis of that, scientists discovered apolypeptide named Ghrelin that contains28amino-acid residues. Thispolypeptide was found in nucleus arcuatus hypothalami and stomach of bothhuman and rat. It’s an endogenous ligand for GHSR. Ghrelin distributes inmany part of central nervous system and peripheral tissues, both in human andnonhuman animals. It has a stimulus effect on hypophysis which leads tosecretion of growth hormone. A lot of work showed Ghrelin and GHSR has awide-ranging impact on regulating physiological functions such as energymetabolism and feeding behavior.Hippocampus is a structure in central neural system. It’s an arcuateeminence outside the dentate gyrus and is located on bottom of inferior cornuof lateral ventricle. Hippocampus and the dentate gyrus make up thehippocampus structure. It participates in many advanced neural actions such asthe formation of behavior, emotion, learning and memory. Researches showthat GHSR distributes in CA1district, CA2district, CA3district andespecially the dentate gyrus. Hippocampus itself does not secrete Ghrelin，butGhrelin secreted by other ligands is able to go through the blood-brain barrier(BBB) into the hippocampus. Further research on Ghrelin and GHSR showedthat exogenous Ghrelin promotes the reparation of hippocampus nerve cells,inhibits apoptosis of hippocampus neural cells. It also regulates learning,memory, emothion and behavior. However, no reports show endogenousGhrelin could influence those physiological processes mentioned above.Research on effect of GHSR and regulating mechanics of GHSR expression inhippocampus has not yet been widely carried out.In recent years, research shows that in the later stage of catch-up growth,Ghrelin level in IUGR rats has no significant difference compared with normalones. Thus we could predict that with the same endogenous Ghrelin level andthe absence of exogenous Ghrelin, the expression level of GHSR could be thepossible factor on regulating memory, learning, emotion and behavior in rats. This experiment would build an IUGR rat model with food restriction duringpregnancy. Rats are divided into IUGR group, catch-up growth group andcontrol group. We would evaluate the changes of learning, memory, emotionand behavior between these three groups, using elevated plus maze test andMorris water-maze test. Furthermore, we would detect the changes of GHSRexpression with western-blot, check the expression of GHSR-mRNA withRT-PCR, through which two methods to explore the relationship between thefactors that influence GHSR expression and the physiological functionsmentioned above.Objective: To observe the changes of learning, memory, emotion andbehavior in IUGR/catch-up growth rats, detect GHSR expression inhippocampus of such rats. To discuss the relationship between the factors thatinfluence GHSR expression and the physiological functions mentioned aboveand explore the possible mechanics.Methods:48healthy female adult SD rats and24health male adult SDrats are randomly put in to24cages in portion of2:1. Then rats mate naturally.Pregnant rats are randomly divided into3groups: food restriction throughoutpregnancy and lactation period; food restriction during pregnancy and no foodrestriction during lactation period; no food restriction throughout pregnancyand lactation period. Juvenile rats who meet the standards are respectively putinto RR group (IUGR group), RC group (Catch-up growth group) and CCgroup(control group). The content of Ghrelin in hippocampus of each groupis detected at day0, day14, day28. Elevated plus maze test are carried out atday28and Morris water-maze test are carried out from day24to day28inorder to observe the changes of learning, memory, emotion and behavior.GHSR expression in hippocampus is detected with western-blot andGHSR-mRNA is detected with RT-PCR.Results:1. Learning and memory Compared with both RC group and CCgroup, escape latency of RR group significantly lengthened(P<0.01), thenumber of times of crossing the platform significantly decreased(P<0.05).Compared with CC group, escape latency of RC group has no significant difference (P>0.05), the number of times of crossing the platform has nosignificant difference(P>0.05).2. Emotion and behavior There are nosignificant difference in escape latency and numbers of time of visiting theclosed arms between the3groups in elevated plus maze test(P>0.05).3.Expression of Ghrelin Western-blot shows that expression of Ghrelin inhippocampus in each group decreased gradually. There are no significantdifference in expression of Ghrelin in hippocampus between the3groups atday0, day14and day28(P>0.05).4. Expression of GHSR Western-blot showsthat compared with both RC group and CC group, expression of GHSR in RRgroup significantly decreased(P<0.01). Compared with CC group, expressionof GHSR in RC group has no significant difference (P>0.05). RT-PCR showsthat compared with both RC group and CC group, expression ofGHSR-mRNA in RR group significantly decreased (P<0.01). Compared withCC group, expression of GHSR-mRNA in RC group has no significantdifference (P>0.05).Conclusion:1. IUGR may reduce the expression of GHSR inhippocampus of rats. Catch-up growth may compensate the loss.2. IUGR mayplay a negative role in learning and memory of juvenile rats. Catch-upgrowth may compensate the loss. IUGR may not be the factor to influenceemotion and behavior of rats.3. IUGR may influence learning and memory ofrats through regulating the expression of GHSR.