Resumen de Long term synaptic reorganization after immobilization stress: a focus on the hippocampus and the TrkB pathway
Post-traumatic stress disorder (PTSD) occurs after exposure to traumatic situations. PTSD is characterized by the development of cognitive impairments includ-ing explicit memory dysfunctions. In fact, the hippocampal formation (HF), a key structure in explicit memory formation, is one of the most affected areas in PTSD, presenting reduced volume and functional abnormalities. Despite stress effects on synaptic plasticity have been related to PTSD, long term stress-related changes in synaptic plasticity remain largely unknown. The study of animal models that mimic symptoms of PTSD patients can be an effective strategy to understand the long term consequences of stress and to find novel drug targets. In this regard, several treatments are used for PTSD, but none of them is reasonably successful. The BDNF/TrkB pathway has been suggested as a novel strategy since animal research has revealed an important role of this pathway in animal PTSD models. Moreover, stress induces important changes in BDNF. Hence, it is reasonable to believe that the use of agonists of the BDNF/TrkB pathway, such as 7,8-dihydroxyflavone (7,8-DHF), could be an effective way to ameliorate some stress effects. To address this issue we studied in rats whether immobilization on boards (IMO) may be a putative PTSD model. We first studied whether a single ex-posure to IMO presents anatomical and behavioral effects similar to those found in PTSD patients and the possible role of changes in synaptic plasticity as a substrate for memory impairment. Second, we investigated whether 7,8-DHF administered hours after stress (therapeutic window) can ameliorate the PTSD-like effect of the IMO and whether IMO-related effects on synaptic plasticity are causally related to memory impairment. IMO induced HF volume decrease and spatial memory impairment similar to those found in other PTSD models or patients. In addition, IMO increased spine density, long term potentiation (LTP), BDNF, HCN1 and Iba1 levels. Therefore, it is reasonable to assume that IMO-induced synaptic plasticity is involved in IMO-related memory impairment. We suggest that IMO induces a disconnection of the memory neural network, which is compensated by posterior reconnection through a homeostatic plasticity process, which even-tually memory. The agonist 7,8-DHF prevented spatial memory impairment and LTP increase with no effect in controls. Taken together, all these results suggest a positive role of 7,8-DHF that sup-ports the idea of a protective role of enhancing the BDNF/TrkB pathway in PTSD and hence the value of 7,8-DHF as a putative treatment for preventing long-term of exposure to traumatic situations.
