Abstract:
A memória é um fenômeno decorrente de um conjunto de processos fisiológicos denominado
plasticidade. Várias formas de plasticidade são necessárias no processo de formação da
memória e também são responsáveis pelo gerenciamento do comportamento. O fenômeno
eletrofisiológico chamado potencialização de longa duração (PLD), cuja ocorrência no
hipocampo merece destaque, foi proposto como sendo o mecanismo de plasticidade
constitutivo das bases da consolidação da memória nesta região encefálica. A importância da
plasticidade na região CA1 do hipocampo se manifesta em diversas formas de aprendizado,
como espacial e condicionamento clássico. Os eventos bioquímicos que culminam na
plasticidade e formação da memória sofrem influência de diversos sistemas de
neurotransmissores e evidências indicam também a participação do sistema purinérgico,
provavelmente através dos receptores ionotrópicos P2X. Receptores purinérgicos do subtipo
P2X7 (P2X7R), largamente distribuídos no sistema nervoso central (SNC), além de possuírem
várias características que os distinguem de outros subtipos de receptores P2X, estão
envolvidos na regulação da liberação de neurotransmissores cruciais para a promoção da PLD
na região hipocampal e formação da memória. Assim, este trabalho objetivou avaliar a
participação dos P2X7R em camundongos geneticamente modificados (KO), que não
expressam o receptor P2X7, e ratos através da exposição destes a diferentes tarefas
comportamentais, bem como avaliar o efeito do enriquecimento ambiental sobre possíveis
déficits mnemônicos resultantes da supressão gênica sobre o receptor P2X7. Os resultados
sugerem que os P2X7R participam tanto da memória aversiva como da memória espacial: o
bloqueio farmacológico com o antagonista específico de P2X7R A-740003 em diferentes
janelas temporais causou prejuízos mnemônicos em ratos submetidos à tarefa do medo
condicionado contextual (MCC), enquanto a deleção do P2X7R causou déficits mnemônicos a
camundongos nas tarefas do labirinto aquático de Morris e no MCC, indicando prejuízos nas
memórias espacial e aversiva, respectivamente. Experimentos com enriquecimento ambiental
sugerem que esta forma de estimulação contribui na reversão dos déficits mnemônicos
causado pela ausência do P2X7R. Por fim, nenhuma alteração na memória de habituação foi
observada em animais com deleção gênica para o P2X7R.
Memory is a phenomenon ensued by a set of physiological processes known as plasticity.
Several forms of plasticity are necessary in the process of memory formation and are also
responsible for the management of the behavior. The electrophysiological phenomenon called
long-term potentiation (LTP), whose occurrence in the hippocampus is generally highlighted,
was proposed to be the underlying plastic mechanism involved in the basis of memory
consolidation in this brain region. The importance of plasticity in the CA1 region of the
hippocampus is observed in several sorts of cognition, such as spatial learning and classic
conditioning. The biochemical events that culminate in plasticity and memory formation are
subject to the influence of several neurotransmission system and evidences suggest also the
participation of the purinergic system in this process, likely through P2X receptors. Purinergic
P2X7 ionotropic receptors (P2X7R), widely distributed through the central nervous system,
possess a number of distinctive characteristics when compared to other P2X receptors and are
involved in the regulation of the release of neurotransmitters that are crucial in the promotion
of hippocampal LTP and memory formation. So, this work aimed to evaluate the participation
of the P2X7R in genetically modified (KO) mice with suppressed expression of the P2X7R and
rats through different behavioral paradigms, as well as to evaluate the effect of environmental
enrichment on potential mnemonic deficits resulting from genetic suppression on the P2X7R.
The results suggest that P2X7R participate on both aversive and spatial memory:
pharmacological blockage with specific P2X7R antagonist A-740003 in different time-frames
elicited mnemonic impairments in rats submitted to the contextual fear conditioning (CFC)
task, and the deletion of P2X7R hampered both spatial and aversive memory of mice subjected
to the Morris water maze and CFC paradigms, respectively. Experiments using mice subjected
to environmental enrichment suggest that this form of stimulation reverses mnemonic
impairments ascribed to the absence of P2X7R. Finally, no alterations were observed in the
habituation memory of P2X7R KO mice.
Innovative studies carried out 50-30 years ago demonstrated that ATP plays a role in cell
signaling. It was soon proposed that ATP activates ionotripic P2X, exerting influence on
neurons as well as on glial cells. Also, ATP release has been implicated in hippocampal long
term potentiation (LTP), whose molecular mechanisms in the hippocampal CA1 region are
much alike those involved in the consolidation of long-term memory (LTM). Evidences show
the presence of moderate-high expression of the P2X7 purinergic receptor (P2X7R) in
presynaptic terminals in the central nervous system, mainly in hippocampal neurons,
contributing to the modulation of neurotransmission in this region. This study aimed to
investigate the participation of the P2X7R in genetically modified (KO) mice with suppressed
expression of the P2X7R and rats through different behavioral paradigms, as well as to
evaluate the effect of environmental enrichment on potential mnemonic deficits resulting
from genetic suppression on the P2X7R. The results suggest that P2X7R participate on both
aversive and spatial memory: pharmacological blockage with specific P2X7R antagonist A-
740003 in different time-frames elicited mnemonic impairments in rats submitted to the
contextual fear conditioning (CFC) task, and the deletion of P2X7R hampered both spatial and
aversive memory of mice subjected to the Morris water maze and CFC paradigms, respectively.
Experiments using mice subjected to environmental enrichment suggest that this form of
stimulation reverses mnemonic impairments ascribed to the absence of P2X7R. Finally, no
alterations were observed in the habituation memory of P2X7R KO mice.
