title: Pharmacological alterations that could underlie radiation-induced changes in associative memory and anxiety.
abstract: It is widely known that ionizing radiation is a physical agent broadly used to kill tumor cells during human cancer therapy. Unfortunately, adjacent normal tissues can concurrently undergo undesirable cell injury. Previous data of our laboratory demonstrated that exposure of developing rats to ionizing radiations induced a variety of behavioral differences respect to controls, including changes in associative memory and in anxiety state. However, there is a lack of data concerning modifications in different related pharmacological intermediaries. Therefore, the aim of the present study was to investigate whether the behavioral differences observed in young animals irradiated at birth might be underlain by early changes in PKCß1 levels which, in turn, could lead to changes in hippocampal GABAergic neurotransmission. Male Wistar rats were irradiated with 5Gy of X rays between 24 and 48 h after birth. Different pharmacological markers related to the affected behavioral tasks were assessed in control and irradiated hippocampus at 15 and 30 days, namely GABAA receptor, GAD65-67, ROS and PKCß1. Results showed that all measured parameters were increased in the hippocampus of 30-days-old irradiated animals. In contrast, in the hippocampus of 15-days-old irradiated animals only the levels of PKCß1 were decreased. These data suggest that PKCß1 might constitute a primary target for neonatal radiation damage on the hippocampus. Therefore, it could be hypothesized that an initial decrease in the levels of this protein can trigger a subsequent compensatory increase that, in turn, could be responsible for the plethora of biochemical changes that might underlie the previously observed behavioral alterations.
authors: 1ª Cátedra de Farmacología, Facultad de Medicina, UBA-CEFyBO-CONICET, Paraguay 2155, piso 15, (1121) Buenos Aires, Argentina.
authors: L G
authors: LG
authors: Caceres
authors: M P
authors: MP
authors: Cid
authors: S L
authors: SL
authors: Uran
authors: M A
authors: MA
authors: Zorrilla Zubilete
authors: N A
authors: NA
authors: Salvatierra
authors: L R
authors: LR
authors: Guelman
mesh_terms: D000818:Animals; D001007:Anxiety / Q000209:etiology*; D005260:Female; D006624:Hippocampus / Q000201:enzymology / Q000378:metabolism / Q000528:radiation effects; D008297:Male; D008568:Memory / Q000528:radiation effects*; D064546:Protein Kinase C beta / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D011963:Receptors, GABA-A / Q000378:metabolism
chemical_list: D017382:Reactive Oxygen Species; D011963:Receptors, GABA-A; D064546:Protein Kinase C beta
keywords: CNS; Ct; EPM; GABA; GAD; HC; Hippocampus; IA; Ionizing radiations; OD; OF; PK; PKCß1; PND; ROS; Rx; central nervous system; control; elevated plus maze; glutamic acid decarboxylase; hippocampus; inhibitory avoidance; irradiated; open field; optical density; postnatal day; protein kinases; reactive oxygen species