O presente estudo demonstrou que no modelo de indução do abrasamento por NIC as fêmeas apresentam uma maior susceptibilidade aos efeitos farmacológicos desta substância, resultante de:
• Desenvolver precocemente as alterações comportamentais inerentes ao abrasamento;
• Apresentar elevada taxa de mortes decorrentes do abrasamento em relação aos animais machos, evidenciando uma maior vulnerabilidade;
• Apresentar níveis elevados do neurotransmissor NE em hipocampo ao longo do desenvolvimento do fenômeno;
• Apresentar um aumento na atividade da enzima Acetilcolinesterase em corpo estriado no fenômeno;
• No abrasamento foi identificado um aumento na imunoexpressão da subunidade NR1 fosforilada de receptor glutamatérgico do tipo NMDA em corpo estriado; • Apresentar um aumento na imunoexpressão do fator de transcrição CREB fosforilado em corpo estriado no fenômeno;
• Ter sido evidenciado elevado níveis do fator neurotrófico BDNF em corpo estriado ao comparar-se com os animais machos no abrasamento.
7 CONCLUSÃO
Os nossos resultados mostram que as fêmeas são mais susceptíveis ao modelo de abrasamento induzido por nicotina, fato este observado através do desenvolvimento precoce das convulsões. Sugere-se que esta susceptibilidade esteja relacionada à hiperexcitabilidade neuronal, decorrente da hiperatividade enzimática de AChE associdada a ativação aumentada de subunidades NMDA-NR1, desencadeando um possível influxo excessivo de Ca2+, que consequentemente, medeia sinalização de
fosfolipases e capaz de ativar p-CREB iniciando a expressão de BDNF, intensificando assim, a neurotoxicidade. Todas estas alterações encontradas favorecem ao aumento da excitabilidade neuronal, e consequentemente, dano celular durante a progressão temporal do fenômeno (Figura 28).
Figura 28: Desenho do mecanismo sugerido à susceptibilidade das fêmeas ao desenvolvimento do abrasamento por NIC.
Fonte: elaborado pelo autor.
Em relação aos machos, novos estudos acerca de mecanismos relacionados ao desenvolvimento do abrasamento deverão ser realizados, a fim de compreender o porquê de serem comportamentalmente mais resistentes, visto que poucas alterações foram encontradas.
Contudo, tornam-se pertinentes estratégias terapêuticas que visem a reversão destas características, uma vez que os mecanismos de abrasamento estão relacionados com alguns distúrbios psiquiátricos.
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