Hippocampus-related behavioral and biochemical alterations during the peri-adolescence period after an early noise exposure: Interactions with environmental stimulation.

BUJAN, GE; GUELMAN LR; RODRIGUEZ GONZÁLEZ, M; MOLINA, SJ; CAPANI, F

Cancún

Congreso; 6th international Symposium on Metabolic Programming and Microbiome and 3rd Meeting of Ibero-American DOHaD chapter; 2018

International Society of Developmental Origins of Health and Disease (DOHAD)

We have previously showed that exposure of immature rats to moderate noise was able to induce hippocampus (HC)-related behavioral and molecular alterations during the peri-adolescence period. Housing of these animals for one week in a standard (S1) or enriched environment (EE1) reversed most behavioral alterations. However, comparative data of HC-related alterations between animals housed during longer intervals and tested at later ages were not obtained yet. Thus, the aim of the present work was the assessment of behavioral parameters of rats exposed to noise at two early developmental ages at different times post exposure as well as to test potential differences in HC oxidative markers (thioredoxins Trx1 and Trx2). In addition, housing in an EE during different intervals was also studied to evaluate the possible reversal of these changes.Male Wistar rats of 7 and 15 days of age (N7 and N15) were exposed to noise (95-97 dB) for 2 hours. After weaning, rats were transferred to an EE, consisting of toys, a wheel, plastic tunnels and ramps, while others were placed in standard cages (S). After one or two weeks, different behavioral tasks were performed and the levels of Trx1and Trx2 were tested through Western blot experiments. Results showed that N7-S1 animals had an increase in risk assessment and exploratory behaviors and a decrease in anxiety-like behaviors, whereas N7-EE1 animals showed a full prevention of these changes. On the other hand, N15-S1 rats showed an increase in anxiety-like behavior and associative memory and a decrease in habituation memory, whereas N15-EE1 only prevented habituation memory alterations. In contrast, behavioral changes found in N7-S1 were not observed in N7-S2. However, the deficit in habituation memory found in N15-S1 animals was still observed in N15-S2 and was reversed by two weeks of EE (N15-EE2).Finally, western blot experiments showed that N7-S1 and N15-S1 rats had an increase in hippocampal Trx1 levels that was reversed when animals were housed in EE1. On the contrary, N15-EE2 failed to normalize Trx1 levels, whereas N7-S2 rats showed a significant decrease in this marker. Finally, no significant changes were observed in Trx2 levels in either group.These findings suggest that rats exposed to noise at different developmental ages might be differentially affected in their behavioral performances, according to the elapsed time between exposure and testing, becoming less evident as development progresses. Furthermore, EE was an effective strategy to reverse alterations in N7 animals whereas only a partial reversion was found in N15 animals. In addition, the ability of EE to reverse behavioral alterations in N15 animals was similar after 1 or 2 weeks of housing in this environment, suggesting that time after exposure and interaction with the environment seem to have a very important role in the development of different cognitive abilities.On the other hand, Trx1 seemed to be more sensitive to the effects of noise exposure than Trx2, being increased in N7 and N15 animals and normalized after one week of EE. Finally, N15 animals continued to show increased levels of Trx1 for one additional week, while N7 rats showed a decrease at this age. Interestingly, no reversion was observed in N15-EE2, whereas normalization was observed in N7-EE2. This difference could be due to the action of compensatory mechanisms triggered in N7 rats that attempt to counteract the imbalance caused by an earlier exposure to noise.