The Gene Expression Change Of Histamine Receptors In Hippocampus Of Rat Led By Agkistrodon Acutus Venom And Its Relationship With Learning And Memory Deficit

Objectives: With the extensive application of molecular biology technique to thelearning and memory research , people can survey the function of a given gene and itsreceptor in learning and memory by the methods of knocking out a gene or transgene.There are various functionary sites of stimulative factors in the brain .Hippocampus is akey target area affected by various neurotransmitters. The previous study demonstratedthat learning and memory deficit is one of the main characteristics of the centralnervous system injured by animal toxin,but its mechanism is still not clear. Therefore,itis very important to elucidate the relationship between the change of the protein andmRNA expression of histamine receptors in rat hippocampus and learning and memorydeficit after injection of Agkistrodon acutus venom.The research will provide someexperimental evidences to further clarify the brain function impairment of the patientswho are bitten by Agkistrodon acutus.Methods: (1)Setting up 5 different time phases after injection into rats with0.65 mg / ml Agkistrodon acutus venom in order to observe the whole behavior of ratsat different time phases.(2)Adopting the Morris water maze to test the spatial learningand memory abilities(.3)The protein and mRNA expression of histamine H1 , H2 and H3receptors in rat hippocampus were examined at different time phases after injection ofAgkistrodon acutus venom by semi-quantitative RT-PCR and Western blot methods.Main results and conclusions: (1)The experimental results of Morris water mazeindicated that Agkistrodon acutus venom induced learning and memory deficit.(2)Theexpression of mRNA and protein of histamine receptors H1, H2, and H3 in rathippocampus were very sensitive to Agkistrodon acutus venom.(3)The proteinexpression of histamine H1 receptor was down-regulation first and then up-regulationled by Agkistrodon acutus venom that meant decrease firstly and increase secondly thenumber of histamine H1 receptor in hippocampus.And this hinted that the density andfunction of histamine H1 receptor had influenced by Agkistrodon acutus venom. Thechange of density and function of histamine H1 receptor protein expression may be oneof the main molecular foundations of learning and memory deficit caused byAgkistrodon acutus venom.(4)The acute up-regulation of histamine H2 receptorexpression after injection of Agkistrodon acutus venom increased the number andfunction of histamine H2 receptor in hippocampus, and which made the formation ofmemory imprint strengthen effectively. The down-regulation of histamine H2 receptorexpression subsequently decreased its density and function which led to learning andmemory deficit. This presented direct evidence that histamine H2 receptor was related tothe learning and memory deficit caused by Agkistrodon acutus venom. The change ofthe number and function of histamine receptors resulted in the protein expression ofhistamine H2 receptor may be one of the main molecular foundations of learning andmemory deficit caused by Agkistrodon acutus venom.(5)The protein expression ofhistamine H3 receptor was down-regulation first and then up-regulation led byAgkistrodon acutus venom,and it indicated that the density of histamine H3 receptordecreased firstly and increased secondly. And it also indicated that the change ofcombinative chance between the cells and histamine in rat hippocampus was decreasedfirstly and increased secondly. The increased density and function of histamine H3receptor enhanced the inhibition of cognitive acquirement in learning andmemory,which resulted in learning and memory deficit consequently. The change of thenumber and function of histamine receptors led by the protein expression up-regulationof histamine H3 receptor may be one of the primary molecular foundations of learningand memory deficit caused by Agkistrodon acutus venom.