masterThesis
Alterações comportamentais induzidas pela administração intrahipocampal de pilocarpina: relevância para o estudo das comorbidades em modelos animais de epilepsia do lobo temporal
Fecha
2018-08-31Registro en:
ARAÚJO, Caroline Pereira de. Alterações comportamentais induzidas pela administração intrahipocampal de pilocarpina: relevância para o estudo das comorbidades em modelos animais de epilepsia do lobo temporal. 2018. 78f. Dissertação (Mestrado em Neurociências) - Instituto do Cérebro, Universidade Federal do Rio Grande do Norte, Natal, 2018.
Autor
Araújo, Caroline Pereira de
Resumen
Temporal Lobe Epilepsy (TLE) is the most common form of focal
epilepsy. The human condition can be modeled in animals by the systemic
administration of pilocarpine (PILO) or kainic acid (KA). The experimental
approach involves an initial insult (status epilepticus - SE) resulting in widespread cell death, structural reorganization, chronic spontaneous seizures and,
impaired performance in memory tasks and anhedonia. The identification of the
anatomical substrates related to the cognitive impairments in those models is
not entirely known, since systemic administration may lead to multiple epileptic
foci. To minimize the impact of spatially distributed, numerous epileptic foci, on
cognitive performance, we present a protocol in which the convulsant agent is
administered directly in the target structure of interest (i.e., straight into the
hippocampus). This approach has been used for KA in mice, but no systematic
study has evaluated the effects of intrahippocampal administration of PILO.
Here, we described the acute and chronic behavioral effects of the
intrahippocampal administration of PILO (4 doses: 70, 245, 400 e 700 µg, in 1
µL) in mice during isoflurane anesthesia. KA (20 mM, 50 nL) and saline (0.9 %)
were used as positive and negative controls, respectively. The results show a
correlation between the severity of the SE and the dose of PILO given
(measured acutely by behavioral scores and indirectly through the evolution of
weight). Interestingly, intrahippocampal PILO injection (N=62) did not elicit tonic
seizures, as commonly observed after systemic administration which
contributed to the low mortality rate of the model (4 out of 63 and 10 out of 11,
respectively). In the chronic phase (1 month after SE), mice treated with high
doses of PILO and KA presented spontaneous seizures. Behavioral tests
revealed that epileptic animals (independent of the convulsive drug used)
present higher stereotyped ambulation (in the open-field) than animals from the
control group. In hippocampal-dependent memory tests, PILO treatment,
especially at high doses, impaired performance in the object recognition task,
but not in the Barnes maze. Animals from the KA group presented impaired
performance in all memory tests compared with the PILO group (high dose).
Taken together, our results demonstrate that ihpc administration of PILO in
mice results in spontaneous and recurrent seizures, as well as moderate cognitive impairment (compatible with comorbidities observed in humans with TLE), and low mortality rate. We believe that the present model has face validity for human TLE, and may serve as an alternative to KA models (which are
expensive) and to the route of administration (high mortality when PILO is
administered systemically).