Thiamine deficiency contributes to synapse and neural circuit defects

BACKGROUND: The previous studies have demonstrated the reduction of thiamine diphosphate is specific to Alzheimer's disease (AD) and causal factor of brain glucose hypometabolism, which is considered as a neurodegenerative index of AD and closely correlates with the degree of cognitive impairment. The reduction of thiamine diphosphate may contribute to the dysfunction of synapses and neural circuits, finally leading to cognitive decline. RESULTS: To demonstrate this hypothesis, we established abnormalities in the glucose metabolism utilizing thiamine deficiency in vitro and in vivo, and we found dramatically reduced dendrite spine density. We further detected lowered excitatory neurotransmission and impaired hippocampal long-term potentiation, which are induced by TPK RNAi in vitro. Importantly, via treatment with benfotiamine, Aß induced spines density decrease was considerably ameliorated. CONCLUSIONS: These results revealed that thiamine deficiency contributed to synaptic dysfunction which strongly related to AD pathogenesis. Our results provide new insights into pathogenesis of synaptic and neuronal dysfunction in AD.

Dehydroascorbic Acid Attenuates Ischemic Brain Edema and Neurotoxicity in Cerebral Ischemia: An in vivo Study

Ischemic stroke results in the diverse phathophysiologies including blood brain barrier (BBB) disruption, brain edema, neuronal cell death, and synaptic loss in brain. Vitamin C has known as the potent anti-oxidant having multiple functions in various organs, as well as in brain. Dehydroascorbic acid (DHA) as the oxidized form of ascorbic acid (AA) acts as a cellular protector against oxidative stress and easily enters into the brain compared to AA. To determine the role of DHA on edema formation, neuronal cell death, and synaptic dysfunction following cerebral ischemia, we investigated the infarct size of ischemic brain tissue and measured the expression of aquaporin 1 (AQP-1) as the water channel protein. We also examined the expression of claudin 5 for confirming the BBB breakdown, and the expression of bcl 2 associated X protein (Bax), caspase-3, inducible nitric oxide synthase (iNOS) for checking the effect of DHA on the neurotoxicity. Finally, we examined postsynaptic density protein-95 (PSD-95) expression to confirm the effect of DHA on synaptic dysfunction following ischemic stroke. Based on our findings, we propose that DHA might alleviate the pathogenesis of ischemic brain injury by attenuating edema, neuronal loss, and by improving synaptic connection.

A patogênese genética e molecular da síndrome de Angelman / The genetic and molecular pathogenesis of the Angelman syndrome

Objetivo: Fornecer uma revisão atualizada em língua portuguesa sobre a síndrome de Angelman, com ênfase nos mecanismos genéticos e moleculares dessa patologia, uma causa de deficiência mental severa que em alguns casos pode apresentar recorrência familiar. Método: Foi feita uma revisão bibliográfica utilizando a base de dados do PubMed, tendo como critérios de busca o termo "Angelman syndrome" isoladamente e combinado com "UBE3A", "clinical", "genetics" e "molecular" no título dos artigos. Dentre esses, foram selecionados artigos de revisão e artigos originais sobre a fisiopatologia da síndrome, com ênfase nos últimos dez anos. Resultados: Utilizando-se "Angelman syndrome" na busca, apareceram cerca de 1.100 artigos, incluindo 240 de revisão. Nos últimos dez anos são mais de 600 artigos, aproximadamente 120 de revisão, 50 por cento dos quais publicados nos últimos cinco anos. Na base de dados SciELO, são apenas nove artigos sobre a síndrome, dos quais três em português e nenhum artigo atual de revisão. Conclusão: Após ter sido uma das principais causas que atraíram atenção ao estudo e ao entendimento dos mecanismos do imprinting genômico, a síndrome de Angelman está agora se revelando como uma patologia das sinapses. Apesar de o entendimento da fisiopatologia molecular da síndrome de Angelman ainda estar longe de ser compreendida, seu estudo está fornecendo uma visão extraordinária sobre os mecanismos que regem a plasticidade sináptica, novamente atraindo a atenção de pesquisadores que trabalham na fronteira do conhecimento.

Objective: The aim of this work is to provide an actualized review in Portuguese language of the main clinical and behavioral features and in particular of the genetic and molecular aspects of Angelman syndrome, a cause of severe intellectual disability, which in rare cases can be recurrent in the family. Method: This paper is a literature review that used as a source of research, scientific papers with the terms "Angelman syndrome" or combined with UBE3A, clinical, genetics, and molecular in their title, retrieved trough the PubMed database. Among those, mainly review articles and original papers about cellular and molecular aspects of the pathology were selected, prioritarily, those published in the last ten years. Results: The term Angelman syndrome retrieved about 1100 papers, including close to 240 review articles. During the last ten years there were over 600 publications, with approximately 120 reviews, 50 percent of whom published in the last five years. The SciELO database was also searched and nine publications about the syndrome were found, three of which in Portuguese and no recent review article. Conclusion: After being one of the main causes to attract attention and stimulate studies to unravel the mechanisms of the genetic imprinting, Angelman syndrome is again in the spotlight because it is revealing itself as pathology of synaptic dysfunction. Albeit still long from understood, the molecular and cellular alterations in Angelman syndrome are allowing an extraordinary insight into the mechanisms which control synaptic plasticity.

EEG Characteristics in Frequency Domain in Synaptic Dysfunction Rat Model / 现代生物医学进展

EEG characteristics in frequency domain were investigated in the frontal lobe, occipital lobe and hippocampus, i.e. cognition - related cortex of synaptic dysfunction model rat, providing electrophysiological basis for further study on plastic extent and nerve regeneration of the damaged neurons. Synaptic dysfunction model was made via microinjecting β - amyloid protein1 - 40 (Aβ1 - 40) into hippocampal CA1 area of rat. Morris water maze behavioral test was performed to evaluate the learning and memory function of model group. Then EEG in the above areas for two groups were recorded. The spectrum for two groups was performed and the characteristics in frequency domain were analyzed. The results showed: (1) The average escape latency in 3rd, 4th, 5th and 6th training times of model group are higher than those of normal. The average escape latency of normal group in 5th training time decreased more markedly than that in 2nd training time, while that of model group in 7th training time decreased more remarkably than that in 2nd training time (P ＜0.05). Without platform, the platform quadrant time percentage of model group was lower than the control (P ＜0.05). (2) Alpha rhythm in EEG of model rat was slowing down; alpha- band power decreased with peek frequency left shifted nearly 2Hz. And the power of delta - band and theta - band in frontal lobe, occipital and hippocampus all increased with different extent. The synaptic dysfunction model rats were made successfully by microinjecting Aβ1 - 40 method. The model rats show the decreased learning and memory dysfunction. EEG frequency spectrum features in model rat show slower alpha rhythm with power amplitude lower or loss, slow waves (delta and theta wave) increasing with higher power amplitude. These can be consistent with the EEG of Alzheimer's disease patients, which can provide electrophysiological basis for further plasticity and nerve regeneration study on the impaired cortex with synaptic dysfunction.

EEG Characteristics in Frequency Domain in Synaptic Dysfunction Rat Model / 现代生物医学进展

EEG characteristics in frequency domain were investigated in the frontal lobe, occipital lobe and hippocampus, i.e. cognition - related cortex of synaptic dysfunction model rat, providing electrophysiological basis for further study on plastic extent and nerve regeneration of the damaged neurons. Synaptic dysfunction model was made via microinjecting β - amyloid protein1 - 40 (Aβ1 - 40) into hippocampal CA1 area of rat. Morris water maze behavioral test was performed to evaluate the learning and memory function of model group. Then EEG in the above areas for two groups were recorded. The spectrum for two groups was performed and the characteristics in frequency domain were analyzed. The results showed: (1) The average escape latency in 3rd, 4th, 5th and 6th training times of model group are higher than those of normal. The average escape latency of normal group in 5th training time decreased more markedly than that in 2nd training time, while that of model group in 7th training time decreased more remarkably than that in 2nd training time (P ＜0.05). Without platform, the platform quadrant time percentage of model group was lower than the control (P ＜0.05). (2) Alpha rhythm in EEG of model rat was slowing down; alpha- band power decreased with peek frequency left shifted nearly 2Hz. And the power of delta - band and theta - band in frontal lobe, occipital and hippocampus all increased with different extent. The synaptic dysfunction model rats were made successfully by microinjecting Aβ1 - 40 method. The model rats show the decreased learning and memory dysfunction. EEG frequency spectrum features in model rat show slower alpha rhythm with power amplitude lower or loss, slow waves (delta and theta wave) increasing with higher power amplitude. These can be consistent with the EEG of Alzheimer's disease patients, which can provide electrophysiological basis for further plasticity and nerve regeneration study on the impaired cortex with synaptic dysfunction.

EEG Characteristics in Frequency Domain in Synaptic Dysfunction Rat Model / 现代生物医学进展

EEG characteristics in frequency domain were investigated in the frontal lobe, occipital lobe and hippocampus, i.e. cognition - related cortex of synaptic dysfunction model rat, providing electrophysiological basis for further study on plastic extent and nerve regeneration of the damaged neurons. Synaptic dysfunction model was made via microinjecting β - amyloid protein1 - 40 (Aβ1 - 40) into hippocampal CA1 area of rat. Morris water maze behavioral test was performed to evaluate the learning and memory function of model group. Then EEG in the above areas for two groups were recorded. The spectrum for two groups was performed and the characteristics in frequency domain were analyzed. The results showed: (1) The average escape latency in 3rd, 4th, 5th and 6th training times of model group are higher than those of normal. The average escape latency of normal group in 5th training time decreased more markedly than that in 2nd training time, while that of model group in 7th training time decreased more remarkably than that in 2nd training time (P ＜0.05). Without platform, the platform quadrant time percentage of model group was lower than the control (P ＜0.05). (2) Alpha rhythm in EEG of model rat was slowing down; alpha- band power decreased with peek frequency left shifted nearly 2Hz. And the power of delta - band and theta - band in frontal lobe, occipital and hippocampus all increased with different extent. The synaptic dysfunction model rats were made successfully by microinjecting Aβ1 - 40 method. The model rats show the decreased learning and memory dysfunction. EEG frequency spectrum features in model rat show slower alpha rhythm with power amplitude lower or loss, slow waves (delta and theta wave) increasing with higher power amplitude. These can be consistent with the EEG of Alzheimer's disease patients, which can provide electrophysiological basis for further plasticity and nerve regeneration study on the impaired cortex with synaptic dysfunction.