Effect Of Substance P Fragment SP1-7 And ERK Pathway In Infant Amnesia

BackgroundLearning and memory is one of the important functions of the brain. Learning and memory are two interrelated processes, learning is the neural process of obtaining new information and new knowledge, but the memory is a neural process of saving and reading information. There are many classification of learning and memory, such as learning is divided into two classify, non-associative learning and associative learning. Memory can be divided into four process, including obtain, consolidate, maintain and recall. Cognitive psychologists classify memory into declarative memory and non-declarative memory, non-declarative memory also includes procedural memory, initialization effect, non-associative learning and associative learning. Classification according to the time, the memory can be divided into instantaneous memory, short-term memory and long-term memory. With the memory is forgotten, including retrograde amnesia and anterograde amnesia.When the earliest memory of humans began? Whether earliest memories of life are forgotten? How to explain this phenomenon of amnesia? According to clinical practice, Freud found that most people could not remember the event happened in early life. Therefore, Freud defined infantile or childhood amnesia, he believed most people hiding memory of 6-8-year-old life events because of its unbearable life events. Now it is thought that human infantile amnesia boundary is 2-4 years old. Psychologists believe that infantile amnesia is a part of autobiographical memory, autobiographical memory is about people experiencing life events memory, and infantile amnesia is the starting point of autobiographical memory. They used language and meta-cognitive development, social development and self-development to explain the infantile amnesia. However, infantile amnesia is not unique to humans. Campbell found that infantile amnesia also exists in rat, and the same in primate. Many researches had been done about infantile amnesia in rat, and we surmise infantile amnesia related brain area including hippocampus, amygdala, medial prefrontal cortex, striatum and striatum fringe areas. The related molecular neurobiology or neurotransmitters include neurotransmitter (y-aminobutyric acid GABA, opioid peptides), intracellular molecules (CAMK II/CAN, PKMQ, extracellular (neurons surrounding network PNNS), hormones (stress hormones, adrenaline) and other (neurogenesis, DNA methylation, Portugal Sugar Sugar). The above-mentioned molecules or neurotransmitters, are associated with learning and memory. As neurogenesis, which is generated neurons from neural stem cells, including split into progenitor cells, and gradually migrate to functional areas, continue to occur plasticity with other neurons establish synaptic contacts resulting in nerve function complete process. Neurogenesis plays an important role in memory formation. And high levels of neurogenesis will promote the formation of new memories, but also can eliminate the memory that has been formed. So neurogenesis have a key role in learning and memory.Substance P (SP) is the first discovery of neuropeptides, the sequence of SP is: H-Arg-Pro-Lys-Pro-Gln-Gln-LPhe-Phe-Gly-Leu-Met-NH2. Substance P belongs to tachykinin family, and tachykinin family includes other neurokinin A (NKA), neurokinin B (NKB) and NKA derivative neuropeptide K (NPK) and neuropeptide y (NPy). There are three types of tachykinin receptors, NK1, NK2 and NK3 receptors, they have G protein coupled receptor. It has high affinity between substance P and NK1, therefore we call NK1 receptor is substance P receptor. NK1 widely distributed in the cerebral cortex, cerebellum, striatum, hippocampus, basal ganglia, olfactory bulb and other central nervous tissue, can also be found in the lung tissue endures peripheral tissues. The role of substance P involve various body systems, it is involved in nerve wound healing, pain transmission, neuroendocrine, bone metabolism, and a variety of neurological disorders such as process and its impact on learning and memory. Whether inject SP into rat peripherally or intracranially, they showed substance P can enhance learning and memory. Substance P fragment, SP1-7, retains the function of substance P on learning and memory. Tomaz trained the rat with passive response and intraperitoneally injected SP (0.05μg/g), SPN 1-7 (0.167μg/g) and SPC 7-11 (0.134μg/g) into rats, showed that SP and SPN1-7 significantly enhanced memory retention. The signal transduction of substance P and NK1 receptor has:1, AC-cAMP-PKA; 2, PLC-IP3/DG-PKC; 3, mitogen-activated protein kinase (MAPK) pathway.MAPK family has four pathways:extracellular signal-regulated kinase (ERK, including ERK1 and ERK2), c-Jun N-terminal kinase (JNK, also known SAPK1), P38 mitogen-activated protein kinase (38 P) and extracellular signal regulated kinase 5 (ERK5). When activated, these receptors trigger the sequential activation of the core classes of kinase in this pathway:the MAP kinase kinase kinases (MAPKKKs), which activates the MAPK kinase (MAPKK), MEK and finally, MEK phosphorylates the MAPKs ERK 1 and 2, both on a threonine and a tyrosine residue. The p-MAPK is transferred to the nucleus, so that some transcription factors phosphorylation, induce intracellular gene expression, and complete of signal transduction. ERK pathway is an important MAPK pathway, that has an important role in the regulation of cell proliferation and differentiation. ERK pathway has an important role in cancer, inflammation, obesity and diabetes and other diseases; involved in ischemia-reperfusion injury in the regulation of apoptosis and autophagy; have a key role in learning and memory. By inducing LTP and behavioral research, confirming the role of ERK in learning and memory. After binding of substance P and its receptor NK1 by ERK signal transduction pathway to complete its physiological functions, such as increased neuronal survival, involved in inflammation, accelerate wound healing, and promote vomiting and analgesic effects. And others such as Amadoro by rat cerebellar granule cells (CGCa) in vitro experiments show granulosa cells NK1 receptor activation can enhance survival of neurons, and by activating AKT and ERK pathway and inhibition of the delayed rectifier potassium current (IK) to achieve.Therefore, this study train rats with passive response, test the memory retention, to further confirmed infancy forgotten phenomenon. After train with passive response, rats were given intraperitoneal injection of substance P fragment SP1-7. Then observed the memory retention, and ERK were detected by immunohistochemistry. Influence of substance P fragment SP1-7 and ERK on infantile amnesia was discussed.Studies include the following two parts:Part I:Study on memory differences of passive avoidance reaction in different age ratsObjectiveUse step-through task to train rats, and test their memory retention, in order to further confirmed infantile amnesia phenomenon.MethodsIt included two group according to age of male SD rat(17-day-old and 60-day-old), each group was 24 cases. Rats were trained in step-through task, test in half an hour after training,2 day and 7 day for memory retention.ResultsThe latent reaction time of adaptive training was no significant difference between P17 and P60(P> 0.05). The latent reaction time of three detection time for one-way ANOVA were significantly different (P<0.05).7 day after training, latent reaction time of P17 and P60 was significant difference (P<0.05); however, half an hour and 2 day after training, latent reaction time of P17 and P60 was no significant difference (P> 0.05).Conclusions7 days after training, memory retention of P17 was significantly reduced reaching the level of adaptive training, while memory retention of P60 was more than P17, showing infantile amnesia phenomenon.Part II:Effect of substance P fragment SP1-7 and ERK pathway in infantile amnesiaObjectiveUse step-through task to train rats, discuss the effect of substance P fragment SP1-7 and ERK pathway in infantile amnesia.MethodsForty-eight 17-day-old male SD rats were divided into three groups, P substance fragment SP1-7 group (1μg/g group, hereinafter referred to SP1 group), P fragment substance SP1-7 group (0.1μg/g group, hereinafter SP0.1 group) and normal saline (NS group). Intraperitoneal inject drug immediately post-training, memory retention were in 2 day and 7 day after training, and ERK were detected by immunohistochemistry.ResultsThe latent reaction time of adaptive training has no significant difference (P> 0.05). LSD multiple comparisons between groups, each two groups has no significant difference (P> 0.05). T test was use to compare P17 and P 60 of three different detection time. The latent reaction time of 2 day after training was significantly longer t than 7 day(P<0.05); There was no significant difference of SP0.1 group (P> 0.05); The latent reaction time of 2 day after training was significantly shorter than 7 day(P<0.05). Groups of each detection time were compared with ANOVA. There was no significant difference in groups of 2 day after training (F=1.29, P> 0.05), each two groups has no significant difference (P> 0.05). There was significant difference in groups of 7 day after training (F= 72.70, P<0.05), each two groups has significant difference (P< 0.05), the sequence of latent reaction time is NS<SP0.1<SP1.ConclusionsSubstance P fragment SP1-7 can enhance memory retention of 7 day after training, SP1-7 and ERK pathway influence learning and memory and infantile amnesia.