Involvement Of LHA In Hippocampal Ghrelin Regulation Of Feeding In Rats

Objective:Ghrelin is an important brain gut peptide involved in feeding regulation.The hippocampus,has been found to be involved in the regulation of learning and memory,is also involved in feeding and gastrointestinal motility regulation.This study aimed to study the effects of hippocampal ghrelin on appetite regulation in rats.Methods:162 healthy male Wistar rats were selected and the body weight was 250-300 g.Rats were implanted with cannulae in CA1 and LHA,and then observed the effect of microinjection of ghrelin receptor(GHSR)antagonist JMV2959 into CA1 on chow intake of rats;Unilateral LHA injection of neuronal excitability toxicity injury drug NMDA was used to observe the effect of CA1 ipsilateral or contralateral injection of ghrelin on chow intake of rats.Rats were implanted with cannulae in ICV,intracerebroventricular injection of OX1 R antagonist SB-334867 was used to observe the effect of microinjection of ghrelin into CA1 on feeding behavior.Rats were given food at 10:00 a.m.every day and food was withdrawn after 4h,continued for 8 days.This rat was defined as a restricted diet rat.Results:(1)The daily 4h chow intake of restricted diet rats significantly increased(P<0.05~0.01).and there was no significant change in the daily 4h chow intake of free diet rats(P>0.05),which was higher than that of rats in restricted diet(P<0.05).The microinjection of 8?g ghrelin receptor antagonist JMV2959 into the CA1 reduced the 4h chow intake significantly(P<0.05)in restricted diet rats,but there was no significant change in 4h chow intake of free diet rats(P>0.05),suggesting that endogenous ghrelin in the hippocampus CA1 region is involved in the regulation of feeding in restricted rats.(2)There was no significant change in the 4h chow intake of restricted diet rats and free die rats(P>0.05)after microinjection of 8?g JMV2959 into LHA,suggesting that endogenous ghrelin has central regional specificity in promoting feeding effects.(3)There was no significant change in the 1h,3h and 5h chow intake of rats with unilateral LHA lesion and injection of ghrelin ipsilateral into CA1(P>0.05);the 1h,3h,and 5h chow intake of rats were significantly increased(P<0.05)when ghrelin was injected into the contralateral hippocampal CA1 region of unilateral LHA lesion.However,in the LHA sham lesion group,the 1h,3h and 5h chow intake of rats were increased significantly(P<0.05)by microinjection of ghrelin into the ipsilateral or contralateral hippocampal CA1 region.It is suggested that the feeding effect of ghrelin in hippocampal CA1 region depends on the complete function of ipsilateral LHA.(4)Fluorogold retrograde tracing combined with immunohistochemistry staining showed that the injection of fluorescent gold into the LHA after 7 days,the fluorescent gold labeled neurons were detected in the hippocampal CA1 region.And ghrelin immunofluorescence staining show that the expression of ghrelin immunoreactivity in the cytoplasm that partially labeled fluorescent gold in hippocampal CA1 region.It is suggested the projection of ghrelin neurons in the hippocampal CA1 region to the LHA.(5)Intracerebroventricular injection of OX1 R receptor antagonist SB-334867,and then microinjected 280 pmol ghrelin into hippocampal CA1 region,there was no significant change in 1h,3h and 5h chow intake of rats(P>0.05).It is suggested that the regulation of ghrelin in CA1 region of hippocampus depends on the participation of OX1 R.Conclusion:Gut derived hormone ghrelin can act on neurons in the hippocampal CA1 region to stimulate appetite in rats.The lateral hypothalamus plays an important role in ghrelin mediated feeding effects in the hippocampus CA1 region.The CA1 region of the hippocampus is associated with ghrelin nerve fibers in the ventrolateral hypothalamus.The ghrelin mediated feeding effects in hippocampal CA1 region also depend on the central orexin-1 receptor.This study provides a new experimental basis for neural circuits to reveal appetite regulation.