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

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

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)

Exposure of immature rats to moderate noise has shown to be able to induce hippocampus (HC)-related behavioral and molecular alterations during the peri-adolescence period. Housing of these animals for one week in an 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 to assess behavioral parameters of rats exposed to noise at two early developmental ages at different times after exposure as well as to test potential differences in HC oxidative markers (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 (N7 and N15) were exposed to noise for 2 h. After weaning, were transferred to EE, consisting of toys, a wheel, plastic tunnels and ramps, while others were placed in standard cages (S). After 1 or 2 weeks, behavioral tasks and hippocampal Trx1and Trx2 levels were executed. Results showed that N7-S1 animals increased risk assessment and exploratory behaviors and decreased anxiety-like behavior, whereas EE1 fully prevented these changes. On the other hand, N15-S1 rats increased anxiety-like behavior and associative memory and decreased habituation memory, whereas EE1 only prevented habituation 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. Finally, western blot experiments showed that N7-S1 and N15-S1 rats increased hippocampal Trx1 levels that were reversed after EE1. On the contrary, whereas N7-S2 rats showed a significant decrease in this marker and EE2 reversed it, N15-EE2 failed to normalize the increased Trx1 levels. No significant changes were observed in Trx2 levels in either group.These findings suggest that rats exposed to noise at 7 and 15 days might be differentially affected in their behavioral performances, according to the elapsed time between exposure and testing, becoming less evident as development progresses. EE was an effective strategy to reverse alterations in N7 animals whereas only a partial reversion was found in N15 animals. In addition, the reversion of behavioral alterations in N15 animals was similar after 1 or 2 weeks of housing in EE, suggesting that time after exposure and interaction with the environment seem to have an important role in the development of cognitive abilities.On the other hand, Trx1 seemed to be more sensitive to noise effects 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.