Avaliação histomorfométrica do efeito do ultrasom pulsado nas falhas ósseas provocadas em fêmures de rato: estudo experimental

SILVA, J. S. P. Avaliação histomorfométrica do efeito do ultrasom pulsado nas falhas ósseas provocadas em fêmures de rato: estudo experimental . 2000. 85 f. Dissertação (Mestrado) – Faculdade de Medicina, Universidade de São Paulo. São Paulo, 2000.

Diferenças funcionais das regiões hipocampais na formação da memória do tipo o quê", "quando" e "onde" em ratos

Episodic memory refers to the recollection of what, where and when a specific event occurred. Hippocampus is a key structure in this type of memory. Computational models suggest that the dentate gyrus (DG) and the CA3 hippocampal subregions are involved in pattern separation and the rapid acquisition of episodic memories, while CA1 is involved in memory consolidation. However there are few studies with animal models that access simultaneously the aspects ‗what-where-when . Recently, an object recognition episodic-like memory task in rodents was proposed. This task consists of two sample trials and a test phase. In sample trial one, the rat is exposed to four copies of an object. In sample trial two, one hour later, the rat is exposed to four copies of a different object. In the test phase, 1 h later, two copies of each of the objects previously used are presented. One copy of the object used in sample trial one is located in a different place, and therefore it is expected to be the most explored object.However, the short retention delay of the task narrows its applications. This study verifies if this task can be evoked after 24h and whether the pharmacological inactivation of the DG/CA3 and CA1 subregions could differentially impair the acquisition of the task described. Validation of the task with a longer interval (24h) was accomplished (animals showed spatiotemporal object discrimination and scopolamine (1 mg/kg, ip) injected pos-training impaired performance). Afterwards, the GABA agonist muscimol, (0,250 μg/μl; volume = 0,5 μl) or saline were injected in the hippocampal subregions fifteen minutes before training. Pre-training inactivation of the DG/CA3 subregions impaired the spatial discrimination of the objects (‗where ), while the temporal discrimination (‗when ) was preserved. Rats treated with muscimol in the CA1 subregion explored all the objects equally well, irrespective of place or presentation time. Our results corroborate the computational models that postulate a role for DG/CA3 in spatial pattern separation, and a role for CA1 in the consolidation process of different mnemonic episodes

Avaliação comportamental e neuroquímica de ratos em dessincronização forçada: possíveis implicações para um modelo animal de oscilações no humor

Bipolar disorder has been growing in several countries. It is a disease with high mortality and has been responsible by the social isolation of the patients. Bipolar patients have alterations in circadian timing system, showing a phase shift in various physiological variables. There are several arguments demonstrating alterations in circadian rhythms may be part of the bipolar disorder pathophysiology. Given the necessity for further elucidation, the goal of this study was to validate the forced desynchronization protocol as an animal model for bipolar disorder. To do this, Wistar rats were submitted to a forced desynchronization protocol which consists in a symmetrical light dark cycle with 22h. Under this protocol, rats dissociate the locomotor activity rhythm into two components: one synchronized to the light / dark cycle with 22h, and another component with period longer than 24 hours following the animal endogenous period. These rhythms with different periods sometimes there is coincidence, which we named CAP (Coincidence Active Phase) and the opposite phase, non-coincidence, called NCAP (Non-Concidence Active Phase). The hypothesis is that in CAP animals present a mania-like behavior and animals in NCAP depressive-like behavior. We found some evidence described in detail throughout this thesis. In sum, the animals under forced desynchronization protocol were more stressed, showed an increase in stereotypic behaviors such as grooming and reduction in other behaviors such as risk assessment and vertical exploration when compared to the control group. The CAP animals showed increased locomotor activity, especially during the dark phase when compared to controls (rats under T24) and less depressive behavior in the forced swim test. The animals in NCAP showed a higher anxiety in elevated plus maze, but they don t have ahnedonia. The animals under dissociation have more labeled 5HT1A cells at the amygdala area, which appoint that they have more amygdala inhibition. Taking these data together, we could partially validated the forced desynchronization protocol as an animal model for mood oscillations

Oscilações Teta no hipocampo do rato durante tarefa de tomada de decisão espacial

The processing of spatial and episodic information during memory tasks depends on hippocampal theta oscillations. In the present study, I investigated the relationship between theta power and choice selection during spatial decision-making. I recorded local field potentials from the CA1 region of rats retrieving reward locations in a 4-arm maze. In trained but not in naïve animals, I observed a significant increase in theta power during decision-making, which could not be explained by changes in locomotion speed. Furthermore, a Bayesian decoder based on theta power predicted choice outcomes in speed-matched trials. The decoding time course revealed that performance increased above chance before the decision moment exclusively for theta power, remaining flat for other frequency bands. These results occurred for trained animals, but no significant prediction could be made for naïve animals. Altogether, the data support a mnemonic function of theta rhythm during spatial decision-making, indicating that these oscillations correlate with the retrieval of memories required for successful decisions

Modelo animal da Doença de Parkinson baseado na expressão de alfa - sinucleína: caracterização comportamental, eletrofisiológica e avaliação dos efei tos da estimulação da medula espinhal

Parkinson disease (PD) is associated with motor symptoms and dopaminergic cell loss in the nigrostriatal pathway. Alpha-synuclein is the major component of the Lewy bodies, the biological hallmarks of disease, and has been associated with familial cases of PD. Recently, the spinal cord stimulation (SCS) showed to be effective to alleviate the Parkinson symptoms in animal models and human patients. In this project, we characterized the motor and electrophysiological effects of alpha-synuclein overexpression in the substantia nigra of rats. We further investigated the effects of spinal electrical stimulation, AMPT and L-dopa administration in this model. Method: Sprague-Dawley rats were injected with empty viral vector or the vector carrying the gene for alpha-synuclein in the substantia nigra, and were tested weekly for 10 weeks in the open field and cylinder tests. A separated group of animals implanted with bilateral electrode arrays in the motor cortex and the striatum were recorded in the open field, during the SCS sessions and the pharmacological experiments. Results: Alpha-synuclein expression resulted in motor asymmetry, observed as the reduction in use of contralateral forepaw in the cylinder test. Animals showed an increase of local field potential activity in beta band three and four weeks after the virus injection, that was not evident after the 5th week. AMPT resulted in a sever parkinsonian state, with reduction in the locomotor activity and significant peak of oscillatory activity in cortex and striatum. SCS was effective to alleviate the motor asymmetry at long term, but did not reduce the corticostriatal low frequency oscillations observed 24 hs after the AMPT administration. These oscillations were attenuated by L-dopa that, even as SCS, was not effective to restore the locomotor activity during the severe dopaminergic depletion period. Discussion: The alpha-synuclein model reproduces the motor impairment and the progressive neurodegenerative process of PD. We demonstrated, by the first time, that this model also presents the increase in low frequency oscillatory activity in the corticostriatal circuit, compatible with parkinsonian condition; and that SCS has a therapeutic effect on motor symptom of this model.

Avaliação histomorfométrica do efeito do ultrasom pulsado nas falhas ósseas provocadas em fêmures de rato: estudo experimental

SILVA, J. S. P. Avaliação histomorfométrica do efeito do ultrasom pulsado nas falhas ósseas provocadas em fêmures de rato: estudo experimental . 2000. 85 f. Dissertação (Mestrado) – Faculdade de Medicina, Universidade de São Paulo. São Paulo, 2000.