Ghrelin is a feeding peptide/hormone that is produced mainly in the gastrointestinal endocrine cells. Before ghrelin and its functions were found, “ghrelin receptors” called Growth hormone secretagogue receptors (GHSR: which is G proteincouples receptor) were acknowledged in the hippocampal formation. Ghrelin is “known as the endogenous ligand for growth hormones (GH) secretagogue (GHS) receptor 1a (GHS-R1a)” (Moon, 2009). Functions of (neuropeptide) ghrelin include releasing GH via the hypothalamus and pituitary pathways and creating a balance in energy by rousing food intake. Another name for ghrelin is “hunger hormone”. This feeding peptide is known to “influence appetite, metabolism, pituitary hormone secretion, gastrointestinal function as well as the cardiovascular and immune systems” (Moon, 2009). Ghrelin is mainly released when the body releases negative energy such as in the state of depression; the hypothalamus signals the GHSR to release ghrelin in order to maintain energy homeostasis. Various researches find beneficial connections between ghrelin and the following: depressive symptoms of chronic stress, regulation of the hippocampal neurogenesis, and controlling of the hippocampal spine synapse density with memory performance. Sidhu 2 The first key relationship is between ghrelin and depressive symptoms (of stress). Chronic stress is responsible for loss of appetite and mood swings which is due to a poor neurobiological mechanism. Investigations regarding these show mice with increasing ghrelin levels via injections or calorie restrictions produce “an anxiolytic and antidepressant like response in the Elevated Plus Maze test and the Forced Swim Test” (Lutter, 2008). The mice that have chronic social defeat stress (which is a rodent model of depression) have an increase in ghrelin levels, whereas the growth hormone secretagogue receptor null mice have the opposite reaction (Lutter, 2008). The activation of ghrelin signaling pathways in the mice due to chronic stress activation is believed to be due to homeostasis adaption, which helps with chronic stress. In summary, an increase in ghrelin levels helps cope with depressive symptoms such as loss of appetite and low ghrelin levels cause more long affecting depressive symptoms such as social avoidance. The second key relationship is between ghrelin and memory. Evident connections are seen between ghrelin regulations in the hippocampal neurogenesis, which “is the process of generating functionally integrated neurons from progenitor cells cells with the tendency to differentiate. Active neurogenesis occurs in the subgranular zone (SGZ) of the dentate gyrus (DG) in the hippocampus” (Moon, 2009). Hippocampal neurogenesis plays a key role in learning and memory. Observations for this mainly focus on adult mice, as there is no report to date about the effect of ghrelin on neurogenesis in adult mammalian. The aims of the studies are to investigate the peripheral administration of ghrelin stimulating proliferation and differentiation of progenitor cells present in the adult Sidhu 3 DG in adult mice. The proliferation of cells is detected with observations in the measurement of BrdU. Observations find “adult mice treated with ghrelin show an increase in BrdU-positive cells. Newly generated neurons were observed in the immunohistochemical study using DCX (Doublecortin: marker of early neural differentiation)” (Moon, 2009). Endogenous (inside) ghrelin plays an important role in neurogenesis because of the immunoneutralization of ghrelin inhibited BrdU incorporation and decreased DCX-positive cells in the SGZ. There is a reduction in BrdU in the adult mice that are immunized against ghrelin. There is an increase of DCX positive cells by exogenous (outside) administration of ghrelin on the other hand. To conclude, observations find that ghrelin helps cell survive in neurogenesis as it protects the hippocampal neurons from cell death. Memory impairment could be caused as a result of neuronal cell loss in the hippocampus. Hippocampal neurogenesis can contribute to epilepsy (Moon, 2009). Specifically in adult mice, ghrelin induced stimulation shows a positive effect on the hippocampal progenitor cells as it may improve cognitive functions-administration of ghrelin known to help learning and memory (Moon, 2009). To sum up, ghrelin is involved in neurogenesis as the hippocampal progenitor cells expressed ghrelin receptors (GHSR). The cause of Ghrelin stimulation is most likely due to increasing cell proliferation. Thus, this finding supports the theory that ghrelin may be used as a potential therapeutic approach for impaired learning and memory processing (Moon, 2009). Next, a deeper understanding of the relationship between ghrelin and memory performance is evident when evaluating ghrelin’s controls on the hippocampal spine Sidhu 4 synapse density and memory performance. When circulating ghrelin reaches the hippocampal formation, it binds to receptors where it not only promotes spine synapse formation, but also alters the neuronal morphology, which generates behavioral outputs (Diano, 2006). The steps to these are as follows; first, the ghrelin binding receptors (GHSR) are identified in the hippocampal formation. The ghrelin then enters the hippocampus and the administration of ghrelin will then rearrange the synaptic organization of anorexigenic neurons (Diano, 2006). As observant in mice “the spine synapse density in the CA1 subfield of the hippocampal formation is higher in ghrelin treated mice than in control treated mice (these observations are found a previously known method, the Elevated Plus Maze)” (Diano, 2006). Then, ghrelin will promote LTP production, which has a positive connection with memory and spatial learning along spine synapse). Synapse numbers vary due to ghrelin levels. Observations show that ghrelin deficient mice underperform the recognition tests but the mice with ghrelin have an increase in memory function in the tests” (Diano, 2006). Low ghrelin levels not only decrease memory function, but also have diseases such as age and obesity associated with low ghrelin levels. A common dementia Alzheimer’s, is promoted by aging and obesity, but there is a possibility that ghrelin supplementation can help Alzheimer patients (Diano, 2006). Ghrelin reduction may decrease hippocampal function/ neural plasticity as it depends mainly on ghrelin signaling. Additionally, although obesity may be stimulated, taking ghrelin may help cognitive impairment (Diano, 2006). In brief, the impact of peripheral ghrelin on hippocampal functions as well as that systemic administrative ghrelin or its analogs has been proven to enhance learning and memory. However this can be impaired by targeted gene disruption, which causes an absence in ghrelin. Sidhu 5 Overall, ghrelin is a beneficial peptide/hormone in medical advancements to help with diseases such as Alzheimer’s. This hormone plays a crucial role in memory as the presence of ghrelin helps with cognitive. It does not only act as a hormone in the gastrointestinal endocrine cells, but it also plays a significant role in the hippocampal functions as well as the cardiovascular system (bloodstream). The effects of ghrelin helps with depressive symptoms of stress, regulation of the hippocampal neurogenesis, and controlling of the hippocampal spine synapse density on memory performance. As a medical advancement, ghrelin can help patients coping with depression that may have difficulties eating as ghrelin is known to help boost appetite through the signals it sends to the body.