An important step for cholinergic transmission involves the vesicular storage of acetylcholine (ACh), a process mediated by the vesicular acetylcholine transporter (VAChT). In order to understand the physiological roles of the VAChT, we developed a genetically altered strain of mice with reduced expression of this transporter. Heterozygous and homozygous VAChT knockdown mice have a 45% and 65% decrease in VAChT protein expression, respectively. VAChT deficiency alters synaptic vesicle filling and affects ACh release. Whereas VAChT homozygous mutant mice demonstrate major neuromuscular deficits, VAChT heterozygous mice appear normal in that respect and could be used for analysis of central cholinergic function. Behavioral analyses revealed that aversive learning and memory are not altered in mutant mice; however, performance in cognitive tasks involving object and social recognition is severely impaired. These observations suggest a critical role of VAChT in the regulation of ACh release and physiological functions in the peripheral and central nervous system.

The vesicular acetylcholine (ACh) transporter (VAChT) mediates ACh storage by synaptic vesicles. However, the VAChT-independent release of ACh is believed to be important during development. Here we generated VAChT knockout mice and tested the physiological relevance of the VAChT-independent release of ACh. Homozygous VAChT knockout mice died shortly after birth, indicating that VAChT-mediated storage of ACh is essential for life. Indeed, synaptosomes obtained from brains of homozygous knockouts were incapable of releasing ACh in response to depolarization. Surprisingly, electrophysiological recordings at the skeletalneuromuscular junction show that VAChT knockout mice present spontaneous miniature end-plate potentials with reduced amplitude and frequency, which are likely the result of a passive transport of ACh into synaptic vesicles. Interestingly, VAChT knockouts exhibit substantial increases in amounts of choline acetyltransferase, high-affinity choline transporter, and ACh. However, the development of the neuromuscular junction in these mice is severely affected. Mutant VAChT mice show increases in motoneuron and nerve terminal numbers. End plates are large, nerves exhibit abnormal sprouting, and muscle is necrotic. The abnormalities are similar to those of mice that cannot synthesize ACh due to a lack of choline acetyltransferase. Our results indicate that VAChT is essential to the normal development of motor neurons and the release of ACh.

No abstract

A hanseníase ainda é considerada um problema de saúde pública no Brasil. O objetivo deste estudo é analisar a situação epidemiológica da hanseníase na microrregião de Almenara/MG segundo sua distribuição espacial e suas relações com as condições socioeconômicas da população. Trata-se de um estudo ecológico. Os resultados colocam a microrregião como uma área hiperendêmica e indicam que os serviços de saúde não estão sendo capazes de detectar todos os casos existentes, contribuindo para manter a cadeia de transmissão da doença. A análise espacial identificou dois clusters, sendo um com coeficientes de detecção acima e outro abaixo do esperado. Acredita-se que os resultados obtidos servirão para balizar a elaboração e implementação de medidas de prevenção e controle da hanseníase na região.

Hansen's disease has a slow evolution, which mostly affects the adult population. Detecting cases in children shows that the endemic continues and there is early exposure of the population to the bacillus. This is an ecological study with the objective of analyzing the occurrence of Hansen's disease in children under fifteen in the Jequitinhonha Valley through epidemiological and operational indicators. The results show that the endemic continues in the region, demonstrating that the health services are not proactive and must implement specific prevention and control measures for this age group in order to reduce the transmission of the disease and the possible damage it can bring to the life of individuals, especially when it affects them in their childhood.