Glycogen synthase kinase-3 (GSK-3) a magic enzyme: its role in diabetes mellitus and glucose homeostasis, interactions with fluroquionlones. A mini-review

Abstract Diabetes mellitus (DM) is a non-communicable disease throughout the world in which there is persistently high blood glucose level from the normal range. The diabetes and insulin resistance are mainly responsible for the morbidities and mortalities of humans in the world. This disease is mainly regulated by various enzymes and hormones among which Glycogen synthase kinase-3 (GSK-3) is a principle enzyme and insulin is the key hormone regulating it. The GSK-3, that is the key enzyme is normally showing its actions by various mechanisms that include its phosphorylation, formation of protein complexes, and other cellular distribution and thus it control and directly affects cellular morphology, its growth, mobility and apoptosis of the cell. Disturbances in the action of GSK-3 enzyme may leads to various disease conditions that include insulin resistance leading to diabetes, neurological disease like Alzheimers disease and cancer. Fluoroquinolones are the most common class of drugs that shows dysglycemic effects via interacting with GSK-3 enzyme. Therefore, it is the need of the day to properly understand functions and mechanisms of GSK-3, especially its role in glucose homeostasis via effects on glycogen synthase.

Resumo O diabetes mellitus (DM) é uma doença não transmissível em todo o mundo, na qual existe nível glicêmico persistentemente alto em relação à normalidade. O diabetes e a resistência à insulina são os principais responsáveis pelas morbidades e mortalidades de humanos no mundo. Essa doença é regulada principalmente por várias enzimas e hormônios, entre os quais a glicogênio sintase quinase-3 (GSK-3) é uma enzima principal e a insulina é o principal hormônio que a regula. A GSK-3, que é a enzima-chave, normalmente mostra suas ações por vários mecanismos que incluem sua fosforilação, formação de complexos de proteínas e outras distribuições celulares e, portanto, controla e afeta diretamente a morfologia celular, seu crescimento, mobilidade e apoptose do célula. Perturbações na ação da enzima GSK-3 podem levar a várias condições de doença que incluem resistência à insulina que leva ao diabetes, doenças neurológicas como a doença de Alzheimer e câncer. As fluoroquinolonas são a classe mais comum de drogas que apresentam efeitos disglicêmicos por meio da interação com a enzima GSK-3. Portanto, é necessário hoje em dia compreender adequadamente as funções e mecanismos da GSK-3, principalmente seu papel na homeostase da glicose via efeitos na glicogênio sintase.

Glycogen synthase kinase-3 (GSK-3) a magic enzyme: it’s role in diabetes mellitus and glucose homeostasis, interactions with fluroquionlones. A mini-review / Glicogênio sintase quinase-3 (GSK-3), uma enzima mágica: seu papel no diabetes mellitus e na homeostase da glicose: interações com fluoroquinolonas. Uma mini-revisão

Diabetes mellitus (DM) is a non-communicable disease throughout the world in which there is persistently high blood glucose level from the normal range. The diabetes and insulin resistance are mainly responsible for the morbidities and mortalities of humans in the world. This disease is mainly regulated by various enzymes and hormones among which Glycogen synthase kinase-3 (GSK-3) is a principle enzyme and insulin is the key hormone regulating it. The GSK-3, that is the key enzyme is normally showing its actions by various mechanisms that include its phosphorylation, formation of protein complexes, and other cellular distribution and thus it control and directly affects cellular morphology, its growth, mobility and apoptosis of the cell. Disturbances in the action of GSK-3 enzyme may leads to various disease conditions that include insulin resistance leading to diabetes, neurological disease like Alzheimer’s disease and cancer. Fluoroquinolones are the most common class of drugs that shows dysglycemic effects via interacting with GSK-3 enzyme. Therefore, it is the need of the day to properly understand functions and mechanisms of GSK-3, especially its role in glucose homeostasis via effects on glycogen synthase.

O diabetes mellitus (DM) é uma doença não transmissível em todo o mundo, na qual existe nível glicêmico persistentemente alto em relação à normalidade. O diabetes e a resistência à insulina são os principais responsáveis pelas morbidades e mortalidades de humanos no mundo. Essa doença é regulada principalmente por várias enzimas e hormônios, entre os quais a glicogênio sintase quinase-3 (GSK-3) é uma enzima principal e a insulina é o principal hormônio que a regula. A GSK-3, que é a enzima-chave, normalmente mostra suas ações por vários mecanismos que incluem sua fosforilação, formação de complexos de proteínas e outras distribuições celulares e, portanto, controla e afeta diretamente a morfologia celular, seu crescimento, mobilidade e apoptose do célula. Perturbações na ação da enzima GSK-3 podem levar a várias condições de doença que incluem resistência à insulina que leva ao diabetes, doenças neurológicas como a doença de Alzheimer e câncer. As fluoroquinolonas são a classe mais comum de drogas que apresentam efeitos disglicêmicos por meio da interação com a enzima GSK-3. Portanto, é necessário hoje em dia compreender adequadamente as funções e mecanismos da GSK-3, principalmente seu papel na homeostase da glicose via efeitos na glicogênio sintase.

Glycogen synthase kinase-3 (GSK-3) a magic enzyme: its role in diabetes mellitus and glucose homeostasis, interactions with fluroquionlones. A mini-review / Glicogênio sintase quinase-3 (GSK-3), uma enzima mágica: seu papel no diabetes mellitus e na homeostase da glicose: interações com fluoroquinolonas. Uma mini-revisão

Diabetes mellitus (DM) is a non-communicable disease throughout the world in which there is persistently high blood glucose level from the normal range. The diabetes and insulin resistance are mainly responsible for the morbidities and mortalities of humans in the world. This disease is mainly regulated by various enzymes and hormones among which Glycogen synthase kinase-3 (GSK-3) is a principle enzyme and insulin is the key hormone regulating it. The GSK-3, that is the key enzyme is normally showing its actions by various mechanisms that include its phosphorylation, formation of protein complexes, and other cellular distribution and thus it control and directly affects cellular morphology, its growth, mobility and apoptosis of the cell. Disturbances in the action of GSK-3 enzyme may leads to various disease conditions that include insulin resistance leading to diabetes, neurological disease like Alzheimers disease and cancer. Fluoroquinolones are the most common class of drugs that shows dysglycemic effects via interacting with GSK-3 enzyme. Therefore, it is the need of the day to properly understand functions and mechanisms of GSK-3, especially its role in glucose homeostasis via effects on glycogen synthase.(AU)

O diabetes mellitus (DM) é uma doença não transmissível em todo o mundo, na qual existe nível glicêmico persistentemente alto em relação à normalidade. O diabetes e a resistência à insulina são os principais responsáveis pelas morbidades e mortalidades de humanos no mundo. Essa doença é regulada principalmente por várias enzimas e hormônios, entre os quais a glicogênio sintase quinase-3 (GSK-3) é uma enzima principal e a insulina é o principal hormônio que a regula. A GSK-3, que é a enzima-chave, normalmente mostra suas ações por vários mecanismos que incluem sua fosforilação, formação de complexos de proteínas e outras distribuições celulares e, portanto, controla e afeta diretamente a morfologia celular, seu crescimento, mobilidade e apoptose do célula. Perturbações na ação da enzima GSK-3 podem levar a várias condições de doença que incluem resistência à insulina que leva ao diabetes, doenças neurológicas como a doença de Alzheimer e câncer. As fluoroquinolonas são a classe mais comum de drogas que apresentam efeitos disglicêmicos por meio da interação com a enzima GSK-3. Portanto, é necessário hoje em dia compreender adequadamente as funções e mecanismos da GSK-3, principalmente seu papel na homeostase da glicose via efeitos na glicogênio sintase.(AU)

Oocytes, embryos and pluripotent stem cells from a biomedical perspective

The veterinary and animal science professions are rapidly developing and their inherent and historical connection to agriculture is challenged by more biomedical and medical directions of research. While some consider this development as a risk of losing identity, it may also be seen as an opportunity for developing further and more sophisticated competences that may ultimately feed back to veterinary and animal science in a synergistic way. The present review describes how agriculture-related studies on bovine in vitro embryo production through studies of putative bovine and porcine embryonic stem cells led the way to more sophisticated studies of human induced pluripotent stem cells (iPSCs) using e.g. gene editing for modeling of neurodegeneration in man. However, instead of being a blind diversion from veterinary and animal science into medicine, these advanced studies of human iPSC-derived neurons build a set of competences that allowed us, in a more competent way, to focus on novel aspects of more veterinary and agricultural relevance in the form of porcine and canine iPSCs. These types of animal stem cells are of biomedical importance for modeling of iPSC-based therapy in man, but in particular the canine iPSCs are also important for understanding and modeling canine diseases, as e.g. canine cognitive dysfunction, for the benefit and therapy of dogs.

Oocytes, embryos and pluripotent stem cells from a biomedical perspective

The veterinary and animal science professions are rapidly developing and their inherent and historical connection to agriculture is challenged by more biomedical and medical directions of research. While some consider this development as a risk of losing identity, it may also be seen as an opportunity for developing further and more sophisticated competences that may ultimately feed back to veterinary and animal science in a synergistic way. The present review describes how agriculture-related studies on bovine in vitro embryo production through studies of putative bovine and porcine embryonic stem cells led the way to more sophisticated studies of human induced pluripotent stem cells (iPSCs) using e.g. gene editing for modeling of neurodegeneration in man. However, instead of being a blind diversion from veterinary and animal science into medicine, these advanced studies of human iPSC-derived neurons build a set of competences that allowed us, in a more competent way, to focus on novel aspects of more veterinary and agricultural relevance in the form of porcine and canine iPSCs. These types of animal stem cells are of biomedical importance for modeling of iPSC-based therapy in man, but in particular the canine iPSCs are also important for understanding and modeling canine diseases, as e.g. canine cognitive dysfunction, for the benefit and therapy of dogs.(AU)

Passion fruit and apple: from residues to antioxidant, antimicrobial and anti-Alzheimers potential / Maracujá e maçã: de resíduos ao potencial antioxidante, antimicrobiano e anti-Alzheimer

The waste in the fruit production chain, including the juice and pulp industries, produces large quantities of leftover husks, seeds and bagasse. This volume of waste generates huge environmental and economic impact. The objective of this research was to determine the potential of using residues from passion fruit (Passiflora edulis) and apple (Malus domestica) varieties in the production of functional flours. Passion fruit flour showed greater reduction of DPPH (EC50%: 50.4μg/mL) radicals, showing antioxidant potential, as well as a more efficient inhibition of Staphylococcus aureus (71.3±1.2μg/mL), with a modest; however efficient, inhibition of acetylcholinesterase (10%). All Apple flours were good antioxidants and the fuji apple flour stood out inhibiting Pseudomonas aeruginosa (78.6±3.1μg/mL). All the residues showed potential for use as a functional product either as a source of antioxidants, a natural (antimicrobial) preservative for dry foods or supplementary use by patients with Alzheimers disease.(AU)

O desperdício na cadeia produtiva de frutos, incluindo as indústrias de suco e polpa, produz grandes quantidades de resíduos, como cascas, sementes e bagaços. Esse volume de resíduos gera impacto ambiental e econômico. O objetivo deste trabalho foi determinar o potencial de aproveitamento de resíduos de maracujá (Passiflora edulis) e de variedades de maçã (Malus domestica) na produção de farinhas funcionais. A farinha de maracujá apresentou maior redução de radicais DPPH (EC50%: 50,4μg/mL), demonstrando potencial antioxidante, maior inibição de Staphylococcus aureus (71,3±1,2μg/mL) e da acetilcolinesterase (10%). Todas as farinhas de maçã foram boas antioxidantes e a fuji destacou-se inibindo Pseudomonas aeruginosa (78,6±3,1μg/mL). Todos os resíduos mostraram potencial para aproveitamento como produto funcional, seja como fonte de antioxidantes, conservante natural (antimicrobiano) para alimentos secos ou uso suplementar no tratamento de Alzheimer.(AU)

In silico analysis of binding interaction of conantokins with NMDA receptors for potential therapeutic use in Alzheimers disease

Abstract Background The N-methyl-D-aspartate (NMDA) receptors are glutamate receptors that play vital roles in central nervous system development and are involved in synaptic plasticity, which is an essential process for learning and memory. The subunit N-methyl D-aspartate receptor subtype 2B (NR2B) is the chief excitatory neurotransmitter receptor in the mammalian brain. Disturbances in the neurotransmission mediated by the NMDA receptor are caused by its overexposure to glutamate neurotransmitter and can be treated by its binding to an antagonist. Among several antagonists, conantokins from cone snails are reported to bind to NMDA receptors. Methods This study was designed to analyze the binding mode of conantokins with NMDA receptors in both humans and rats. To study interactions, dockings were performed using AutoDock 4.2 and their results were further analyzed using various computational tools. Results Detailed analyses revealed that these ligands can bind to active site residues of both receptors as reported in previous studies. Conclusions In light of the present results, we suggest that these conantokins can act as antagonists of those receptors and play an important role in understanding the importance of inhibition of NMDA receptors for treatment of Alzheimers disease.

Calcium homeostasis modulator 1 ( CALHM1 ) polymorphisms in cattle

ABSTRACT: The calcium homeostasis modulator 1 gene (CALHM1), which is located on chromosome 10 in humans and on chromosome 26 in cattle, is a transmembrane glycoprotein that controls the cytosolic calcium concentrations. Altered calcium homeostasis has been associated with several neurodegenerative disorders, including Alzheimers disease (AD). In a recent study, single nucleotide polymorphisms (SNPs) of CALHM1 have been associated with sporadic Creutzfeldt-Jakob disease (CJD). The protein sequence of human CALHM1 shows 93% homology with bovine CALHM1. Although SNPs of human CALHM1 have been correlated with human prion disease, polymorphisms of the bovine CALHM1 gene have not been reported in cattle thus far. To investigate polymorphisms of the bovine CALHM1 gene in Korean native cattle, we analyzed the open reading frame (ORF) of this gene in 175 Hanwoo and 141 Holstein cattle. We observed five SNPs: c.219C>T (rs380966453), c.357C>T (rs385969338), and c.869A>G (rs516301908) within the ORF region of two exons; and c.552+92A>G (rs481706737) and c.553-3A>C (rs448524869) in the intron of bovine CALHM1. Among the three SNPs that are in the ORF region of bovine CALHM1, the genotype and allele frequencies of the c.869A>G (p.His290Arg) and c.219C>T (p.Asn73Asn) SNPs were significantly different between Hanwoo and Holstein cattle (P 0.0001). Haplotype analysis showed that haplotypes ht2, ht3 and ht5 were also significantly different in these two cattle breeds. This study provides the first genetic analysis of the bovine CALHM1 gene in cattle.

In silico analysis of binding interaction of conantokins with NMDA receptors for potential therapeutic use in Alzheimer's disease

Background The N-methyl-D-aspartate (NMDA) receptors are glutamate receptors that play vital roles in central nervous system development and are involved in synaptic plasticity, which is an essential process for learning and memory. The subunit N-methyl D-aspartate receptor subtype 2B (NR2B) is the chief excitatory neurotransmitter receptor in the mammalian brain. Disturbances in the neurotransmission mediated by the NMDA receptor are caused by its overexposure to glutamate neurotransmitter and can be treated by its binding to an antagonist. Among several antagonists, conantokins from cone snails are reported to bind to NMDA receptors. Methods This study was designed to analyze the binding mode of conantokins with NMDA receptors in both humans and rats. To study interactions, dockings were performed using AutoDock 4.2 and their results were further analyzed using various computational tools. Results Detailed analyses revealed that these ligands can bind to active site residues of both receptors as reported in previous studies. Conclusions In light of the present results, we suggest that these conantokins can act as antagonists of those receptors and play an important role in understanding the importance of inhibition of NMDA receptors for treatment of Alzheimer's disease.(AU)

In silico analysis of binding interaction of conantokins with NMDA receptors for potential therapeutic use in Alzheimer's disease

Background The N-methyl-D-aspartate (NMDA) receptors are glutamate receptors that play vital roles in central nervous system development and are involved in synaptic plasticity, which is an essential process for learning and memory. The subunit N-methyl D-aspartate receptor subtype 2B (NR2B) is the chief excitatory neurotransmitter receptor in the mammalian brain. Disturbances in the neurotransmission mediated by the NMDA receptor are caused by its overexposure to glutamate neurotransmitter and can be treated by its binding to an antagonist. Among several antagonists, conantokins from cone snails are reported to bind to NMDA receptors. Methods This study was designed to analyze the binding mode of conantokins with NMDA receptors in both humans and rats. To study interactions, dockings were performed using AutoDock 4.2 and their results were further analyzed using various computational tools. Results Detailed analyses revealed that these ligands can bind to active site residues of both receptors as reported in previous studies. Conclusions In light of the present results, we suggest that these conantokins can act as antagonists of those receptors and play an important role in understanding the importance of inhibition of NMDA receptors for treatment of Alzheimer's disease.(AU)

Potencial inibitório in vitro de chás comerciais e da quercetina sobre a atividade de acetilcolinesterase cerebral em cães / The inhibitory potential in vitro of commercial teas and quercetin on cerebral acetylcholinesterase activity in dogs

Com o aumento na expectativa de vida dos animais de companhia há um maior aparecimento de doenças neurodegenerativas, como a Disfunção Cognitiva Canina (DCC). A DCC apresenta diversas semelhanças à Doença de Alzheimer (DA) presente em seres humanos. Entre estas semelhanças é possível citar o nível reduzido de acetilcolina, o que justifica a busca por tratamentos que tenham como foco, a inibição da acetilcolinesterase (AChE), enzima responsável pela degradação deste neurotransmissor. Neste trabalho foi avaliado o potencial inibitório dos chás de maçã, de hortelã e de chá verde sobre a atividade de AChE presente em cérebro de cães. O chá verde foi o chá mais eficaz na inibição desta enzima, apresentando uma IC50 de aproximadamente 1.7 mg/mL. A quercetina, flavonol que segundo a literatura está presente no chá verde e ausente nos chás de maçã e hortelã, pode ser um dos constituintes responsáveis por esta inibição. Desta forma, também foi avaliado o potencial anticolinesterásico da quercetina em cérebro canino, obtendo-se uma IC50 de 0,41 mM. Uma vez que a quercetina já tem sido utilizada na medicina veterinária para outros fins, o potencial anticolinesterásico deste flavonol em cérebro canino mostra-se de grande relevância para os estudos da DCC.

Canine Cognitive Dysfunction (CCD) is a neuodegenerative disease with very similar characteristics to humans Alzhemer’s disease. Currently, the increase of pets life expectancy leads to the more frequent appearance of neurodegenerative diseases in these species. Among the main hypotheses for the appearance of CCD has the reduction of acetylcholine levels in the synaptic cleft. This hypothesis justifies many researches that search CCD treatment based on acetylcholinesterase (AChE) inhibition, an acetylcholine degrading enzyme. In this work, inhibitory potential of some commecial teas (apple tea, peppermint tea and green tea) toward brain AChE activity of dogs was evaluated. Green tea is tea more effective to inhibit this enzyme, getting a IC 50 of approximately 1.7 mg / mL. Quercetin, flavonol which according to the literature is present in green tea and absent in apple and peppermint teas, may be one of the molecules that contribute to AChE inhibition. In this way, quercetn anticholinesterase potential in canine brain was also evaluated, obtaining an IC 50 of 0.41 mM. Since quercetin has already been used in veterinary medicine for other fins, the anticholinesterase potential of this flavonol toward canine brain is of great relevance for CCD studies.

Potencial inibitório in vitro de chás comerciais e da quercetina sobre a atividade de acetilcolinesterase cerebral em cães / The inhibitory potential in vitro of commercial teas and quercetin on cerebral acetylcholinesterase activity in dogs

Com o aumento na expectativa de vida dos animais de companhia há um maior aparecimento de doenças neurodegenerativas, como a Disfunção Cognitiva Canina (DCC). A DCC apresenta diversas semelhanças à Doença de Alzheimer (DA) presente em seres humanos. Entre estas semelhanças é possível citar o nível reduzido de acetilcolina, o que justifica a busca por tratamentos que tenham como foco, a inibição da acetilcolinesterase (AChE), enzima responsável pela degradação deste neurotransmissor. Neste trabalho foi avaliado o potencial inibitório dos chás de maçã, de hortelã e de chá verde sobre a atividade de AChE presente em cérebro de cães. O chá verde foi o chá mais eficaz na inibição desta enzima, apresentando uma IC50 de aproximadamente 1.7 mg/mL. A quercetina, flavonol que segundo a literatura está presente no chá verde e ausente nos chás de maçã e hortelã, pode ser um dos constituintes responsáveis por esta inibição. Desta forma, também foi avaliado o potencial anticolinesterásico da quercetina em cérebro canino, obtendo-se uma IC50 de 0,41 mM. Uma vez que a quercetina já tem sido utilizada na medicina veterinária para outros fins, o potencial anticolinesterásico deste flavonol em cérebro canino mostra-se de grande relevância para os estudos da DCC.(AU)

Canine Cognitive Dysfunction (CCD) is a neuodegenerative disease with very similar characteristics to humans Alzhemers disease. Currently, the increase of pets life expectancy leads to the more frequent appearance of neurodegenerative diseases in these species. Among the main hypotheses for the appearance of CCD has the reduction of acetylcholine levels in the synaptic cleft. This hypothesis justifies many researches that search CCD treatment based on acetylcholinesterase (AChE) inhibition, an acetylcholine degrading enzyme. In this work, inhibitory potential of some commecial teas (apple tea, peppermint tea and green tea) toward brain AChE activity of dogs was evaluated. Green tea is tea more effective to inhibit this enzyme, getting a IC 50 of approximately 1.7 mg / mL. Quercetin, flavonol which according to the literature is present in green tea and absent in apple and peppermint teas, may be one of the molecules that contribute to AChE inhibition. In this way, quercetn anticholinesterase potential in canine brain was also evaluated, obtaining an IC 50 of 0.41 mM. Since quercetin has already been used in veterinary medicine for other fins, the anticholinesterase potential of this flavonol toward canine brain is of great relevance for CCD studies.(AU)

Use of clinical form for recognition of cognitive disturbance in elderly dogs / Utilização de formulário clínico para reconhecimento de distúrbio cognitivo em cães idosos

The canine cognitive disorders (DCC) is a neurobehavioral syndrome that affects elderly animals, characterized by deficiencies in learning, memory and space perception, as well as changes in social interactions and sleep pattern. In spite of its common occurrence, it is not diagnosed and treated, since the neu­rocognitive behavioral changes are commonly considered as part of the normal aging process by the owners. This study evaluated the cognitive function in 30 dogs over than 8 years old, through a behavioral form, it was observed that 93% of the animals showed alteration in more than one category. The categories most affected were Category B (relationships and social behavior) with 78,6% (n= 22) of the total of cases and Category C (activity level) also in 78,6% of cases. No differences were observed between gender nor between the age and the pre­sence of signs of DCC.

O distúrbio cognitivo canino (DCC) é uma síndrome neurocomportamental que acomete animais idosos, caracterizado por deficiências na aprendizagem, memória e percepção espacial, bem como alterações em interações sociais e padrão de sono. Apesar de ocorrência comum é pouco diagnosticado e tratado, uma vez que as mudanças comportamentais neuro cognitivas são comumente considerados como parte do processo normal de envelhecimento pelos proprietários. Este estudo avaliou a função cognitiva de 30 cães com mais de oito anos de idade, através de um formulário comportamental, observou-se que 93% dos animais apresentaram alteração em mais de uma categoria. As categorias mais acometidas foram Categoria B (relacionamentos e comportamento social) com 78,6% (n=22) dos casos e Categoria C (nível de atividade) também com 78,6% dos casos. Não foram observadas diferenças entre gênero ou na correção entre idade e presença de sinais de DCC.

Use of clinical form for recognition of cognitive disturbance in elderly dogs / Utilização de formulário clínico para reconhecimento de distúrbio cognitivo em cães idosos

The canine cognitive disorders (DCC) is a neurobehavioral syndrome that affects elderly animals, characterized by deficiencies in learning, memory and space perception, as well as changes in social interactions and sleep pattern. In spite of its common occurrence, it is not diagnosed and treated, since the neu­rocognitive behavioral changes are commonly considered as part of the normal aging process by the owners. This study evaluated the cognitive function in 30 dogs over than 8 years old, through a behavioral form, it was observed that 93% of the animals showed alteration in more than one category. The categories most affected were Category B (relationships and social behavior) with 78,6% (n= 22) of the total of cases and Category C (activity level) also in 78,6% of cases. No differences were observed between gender nor between the age and the pre­sence of signs of DCC.(AU)

O distúrbio cognitivo canino (DCC) é uma síndrome neurocomportamental que acomete animais idosos, caracterizado por deficiências na aprendizagem, memória e percepção espacial, bem como alterações em interações sociais e padrão de sono. Apesar de ocorrência comum é pouco diagnosticado e tratado, uma vez que as mudanças comportamentais neuro cognitivas são comumente considerados como parte do processo normal de envelhecimento pelos proprietários. Este estudo avaliou a função cognitiva de 30 cães com mais de oito anos de idade, através de um formulário comportamental, observou-se que 93% dos animais apresentaram alteração em mais de uma categoria. As categorias mais acometidas foram Categoria B (relacionamentos e comportamento social) com 78,6% (n=22) dos casos e Categoria C (nível de atividade) também com 78,6% dos casos. Não foram observadas diferenças entre gênero ou na correção entre idade e presença de sinais de DCC.(AU)

Redução do uso de animais através da bioinformática: técnicas in-silico apontam alvos moleculares / Reduction in the utilization of animals through bioinformatics: in-silico techniques point towards molecular targets

Model animals are indispensable in the advancement of life sciences. Computational analyses can save time and reduce the number of animals needed. Bioinformatics offer tools that support research through in-silico evaluations. Our aim was to study the function of exercise-linked genes, focusing on disease pathways, envisaging the discovery of new molecular targets for the use in animal model studies. This research was part of two projects approved by the local Ethics Committee (CEUA/UECE) in 04/2014 (1592060/2014) and 07/2015 (2542310/2015). Human genes linked to physical exercise were classified by the pathways using the enrichment tool Enrichnet. Statistical analyses (ANOVA) were used using the Fisher test (q-value). Strong correlations were found with neurodegenerative, cardiovascular and immunologic diseases. Within neurodegenerative diseases, physical exercise was found to be linked to Parkinson’s (q-value 1.6 X10-17), Alzheimer’s (q-value 3.9 X10-16) and Huntington disease (q-value 1.9 X10-15). Within cardiovascular diseases linked to exercise there is hypertrophic cardiomyopathy (q-value 8.5 X10-15). A large number of genes linked to exercise were found to participate in disease linked metabolic pathways. Concluding, after evaluating genes linked to physical exercise and disease pathways, new molecular targets for the use in model animal studies were revealed.

Redução do uso de animais através da bioinformática: técnicas in-silico apontam alvos moleculares / Reduction in the utilization of animals through bioinformatics: in-silico techniques point towards molecular targets

Model animals are indispensable in the advancement of life sciences. Computational analyses can save time and reduce the number of animals needed. Bioinformatics offer tools that support research through in-silico evaluations. Our aim was to study the function of exercise-linked genes, focusing on disease pathways, envisaging the discovery of new molecular targets for the use in animal model studies. This research was part of two projects approved by the local Ethics Committee (CEUA/UECE) in 04/2014 (1592060/2014) and 07/2015 (2542310/2015). Human genes linked to physical exercise were classified by the pathways using the enrichment tool Enrichnet. Statistical analyses (ANOVA) were used using the Fisher test (q-value). Strong correlations were found with neurodegenerative, cardiovascular and immunologic diseases. Within neurodegenerative diseases, physical exercise was found to be linked to Parkinsons (q-value 1.6 X10-17), Alzheimers (q-value 3.9 X10-16) and Huntington disease (q-value 1.9 X10-15). Within cardiovascular diseases linked to exercise there is hypertrophic cardiomyopathy (q-value 8.5 X10-15). A large number of genes linked to exercise were found to participate in disease linked metabolic pathways. Concluding, after evaluating genes linked to physical exercise and disease pathways, new molecular targets for the use in model animal studies were revealed.(AU)

Neuroactive compounds obtained from arthropod venoms as new therapeutic platforms for the treatment of neurological disorders

The impact of neurological disorders in society is growing with alarming estimations for an incidence increase in the next decades. These disorders are generally chronic and can affect individuals early during productive life, imposing real limitations on the performance of their social roles. Patients can have their independence, autonomy, freedom, self-image, and self-confidence affected. In spite of their availability, drugs for the treatment of these disorders are commonly associated with side effects, which can vary in frequency and severity. Currently, no effective cure is known. Nowadays, the biopharmaceutical research community widely recognizes arthropod venoms as a rich source of bioactive compounds, providing a plethora of possibilities for the discovery of new neuroactive compounds, opening up novel and attractive opportunities in this field. Several identified molecules with a neuropharmacological profile can act in the central nervous system on different neuronal targets, rendering them useful tools for the study of neurological disorders. In this context, this review aims to describe the current main compounds extracted from arthropod venoms for the treatment of five major existing neurological disorders: stroke, Alzheimers disease, epilepsy, Parkinsons disease, and pathological anxiety.(AU)

Neuroactive compounds obtained from arthropod venoms as new therapeutic platforms for the treatment of neurological disorders

The impact of neurological disorders in society is growing with alarming estimations for an incidence increase in the next decades. These disorders are generally chronic and can affect individuals early during productive life, imposing real limitations on the performance of their social roles. Patients can have their independence, autonomy, freedom, self-image, and self-confidence affected. In spite of their availability, drugs for the treatment of these disorders are commonly associated with side effects, which can vary in frequency and severity. Currently, no effective cure is known. Nowadays, the biopharmaceutical research community widely recognizes arthropod venoms as a rich source of bioactive compounds, providing a plethora of possibilities for the discovery of new neuroactive compounds, opening up novel and attractive opportunities in this field. Several identified molecules with a neuropharmacological profile can act in the central nervous system on different neuronal targets, rendering them useful tools for the study of neurological disorders. In this context, this review aims to describe the current main compounds extracted from arthropod venoms for the treatment of five major existing neurological disorders: stroke, Alzheimers disease, epilepsy, Parkinsons disease, and pathological anxiety.

Déficit de memória em ratos submetidos à indução a doença de alzheimer por infusão intracerebral de beta-amiloide1-42 / Memory deficit in rats submitted to induction alzheimer's disease in infusion of intracerebral beta-amiloide1-42

Alzheimer's disease (AD) was established as the neurodegenerative dementia, which leads to progressive and irreversible cognitive decline, memory loss, attention and judgment. It is characterized by molecular injuries resulting from the accumulation of charged neuritic plaques of β-amyloid and neurofibrillary tangles causing oxidative damage and inflammatory. Thus, the aim of this study was to evaluate the learning and memory of rats seven days after infusion of β-amiloide1-42. The β-amiloide1-42 was prepared in saline protein (1ug / uL) and incubated at 37 ° C for three days to form the aggregate. The animals were anesthetized with the combination of ketamine (100 mg / kg) and xylazine (10 mg / kg) intraperitoneally, and fixed in a stereotaxic route. The aggregate was infused directly in the hippocampus (5UL bilaterally) in the coordinates, AP: -3.5 mm; LL: ± 2.0 mm; DV: -3.5. The learning and memory was assessed using the Morris water maze. The apparatus consists of a circular water tank (120 cm diameter and 60 cm high) with an escape platform (12.5 cm in diameter and 38 cm high) positioned invisible to the mice 2 cm below the water level. The tank was divided by imaginary lines (N, S, L, and O) in four quadrants (1, 2, 3 and 4) and identified by the same geometrical symbols, which remained the same throughout the study. The animals were placed facing the geometric shapes and the exhaust time measured during four consecutive days (training). In the fifth and final day it was taken to the escape platform and computed the total residence time in the target quadrant (test). The maximum time for each step was 60s. This study was approved by Ethics Committee for Animal Use (CEUA) of the State University of Ceará (UECE) by the number 2542310/2015. To analyze the learning we used the ANOVA two way with Bonferroni post-test. To verify differences in memory between the groups we used the Student t test. P <0.05 significance level was adopted[...]

Déficit de memória em ratos submetidos à indução a doença de alzheimer por infusão intracerebral de beta-amiloide1-42 / Memory deficit in rats submitted to induction alzheimer's disease in infusion of intracerebral beta-amiloide1-42

Alzheimer's disease (AD) was established as the neurodegenerative dementia, which leads to progressive and irreversible cognitive decline, memory loss, attention and judgment. It is characterized by molecular injuries resulting from the accumulation of charged neuritic plaques of β-amyloid and neurofibrillary tangles causing oxidative damage and inflammatory. Thus, the aim of this study was to evaluate the learning and memory of rats seven days after infusion of β-amiloide1-42. The β-amiloide1-42 was prepared in saline protein (1ug / uL) and incubated at 37 ° C for three days to form the aggregate. The animals were anesthetized with the combination of ketamine (100 mg / kg) and xylazine (10 mg / kg) intraperitoneally, and fixed in a stereotaxic route. The aggregate was infused directly in the hippocampus (5UL bilaterally) in the coordinates, AP: -3.5 mm; LL: ± 2.0 mm; DV: -3.5. The learning and memory was assessed using the Morris water maze. The apparatus consists of a circular water tank (120 cm diameter and 60 cm high) with an escape platform (12.5 cm in diameter and 38 cm high) positioned invisible to the mice 2 cm below the water level. The tank was divided by imaginary lines (N, S, L, and O) in four quadrants (1, 2, 3 and 4) and identified by the same geometrical symbols, which remained the same throughout the study. The animals were placed facing the geometric shapes and the exhaust time measured during four consecutive days (training). In the fifth and final day it was taken to the escape platform and computed the total residence time in the target quadrant (test). The maximum time for each step was 60s. This study was approved by Ethics Committee for Animal Use (CEUA) of the State University of Ceará (UECE) by the number 2542310/2015. To analyze the learning we used the ANOVA two way with Bonferroni post-test. To verify differences in memory between the groups we used the Student t test. P <0.05 significance level was adopted[...](AU)