Molecular bases of environmental enrichment cognitive neuroprotection in an animal model of cerebral ischemia.
Name: LARA VEZULA GONÇALVES
Type: MSc dissertation
Publication date: 07/07/2017
Advisor:
Name |
Role |
|---|---|
| CRISTINA MARTINS E SILVA | Advisor * |
Examining board:
| Name |
Role |
|---|---|
| BRENO VALENTIM NOGUEIRA | Internal Examiner * |
| CRISTINA MARTINS E SILVA | Advisor * |
| LÍVIA CARLA DE MELO RODRIGUES | External Alternate * |
| RITA GOMES WANDERLEY PIRES | Co advisor * |
| SUELY GOMES DE FIGUEIREDO | Internal Alternate * |
Summary: Stroke is considered a major cause of global morbidity. This pathological condition can result in motor, cognitive and sensory alterations. Currently, there are no effective treatments for post-stroke cognitive impairment. Among the available treatments, the use of non-pharmacological therapies has shown to be efficient in preventing and/or treating diseases of the central nervous system. One of these therapies involves the enriched environment (EE) which is a set of external stimuli that aid in the recovery of brain tissue after insult. In addition, EE may also be used as a preconditioning method to induce cerebral tolerance in an ischemic event. Animals pre-conditioned to an EE presented tolerance when submitted to ischemia with consequent improvement in motor function and in mnemonic processes, such as learning and memory. However, the molecular mechanisms involved in this tolerance are not yet clear. Therefore, it becomes relevant to the identification of the mechanisms of neuroprotection provoked by the preconditioning to the EE in murine model of AVE. In the present study, freshly weaned C57Bl/6 mice were kept for five weeks in EE or standard environment (SC). After that period they were divided into sham/standard environment (SS, n = 30), sham/enriched environment (ES, n = 18), ischemic/standard environment (SI, n = 39) and ischemic/ enriched environment (EI, n = 21). The animals in the ischemia group underwent bilateral occlusion of the common carotid arteries for 30 minutes. At the same time, the animals of the sham group underwent a similar surgical procedure, however, without the occlusion of the arteries. The infarct area was checked by staining the 2, 3, 5-triphenyltetrazolium chloride. Cognitive parameters were evaluated by means of object recognition tast (TRO) and Y-maze. The relative expression of the genes of the NMDA glutamatergic receptor subunits (GluN1, GluN2A, GluN2B and GluN2C), the cholinergic receptors muscarinic M1 and ionotropic alpha 7, inflammatory markers GFAP, IL-1β, as well as BDNF were evaluated in the hippocampus. In addition, the tissue levels of the neurotransmitter glutamate in the aforementioned regions were analyzed. The EE paradigm used prevented short-term memory deficit caused by ischemia, significantly reducing the infarct volume. Our study strongly suggests that cognitive improvement induced by the EE can be promoted by reducing inflammatory cytokine IL1-β expression and increasing GFAP in ischemic animals. The EE did not change the working memory, evaluated in the Y-maze.
Keywords: environmental enrichment, cerebral ischemia, neuroprotection, learning and memory.
