Lafora's disease in a free-ranging toco toucan (Ramphastos toco) with neurologic disease

Lafora's disease is a genetic disease associated to mutations in genes that encodes laforin and malin, which results in intracellular polyglucan storage. The present report describes a case of Lafora's disease in a toco toucan with episodes of incoordination and myoclonus that resulted in traumatic lesions and fracture of the left hindlimb. The bird was euthanized and submitted to necropsy. Microscopically there were abundant PAS-positive and diastasis-resistant Lafora's inclusion bodies in neurons in the cerebellum, supporting the diagnosis of Lafora's disease.(AU)

Potential of marine compounds in the treatment of neurodegenerative diseases: a review / Potencial de compostos marinhos no tratamento de doenças neurodegenerativas: uma revisão

Neurodegenerative diseases (ND) are characterized, especially, by the progressive loss of neurons, resulting in neuropsychomotor dysfunctions. Even with a high prevalence, NDs are treated with drugs that alleviate the symptoms of patients, but which develop adverse events and still do not inhibit the progression of the disease. Thus, within a new pharmacological perspective, this review aimed to verify the therapeutic potential of natural compounds of marine origin against ND. For this, an integrative review was carried out, according to the PRISMA methodology, which included steps such as: search, pre-selection and inclusion of articles. The results described revealed species such as Acaudina malpodioides, Holothuria scabra and Xylaria sp., which presented important evidence in relation to Alzheimer's, reducing the generation of ROS, presenting neuroprotective effects and reducing the concentration of Aß peptide. Regarding Parkinson's disease (PD), another example of ND, the bioactive compounds from Holothuria scabra and Xylaria sp., showed to be able to reduce the degeneration of dopaminergic neurons, reduce the deposition of alpha synuclein and reduce the formation of Mutant Huntingtin protein (Mhtt). The other marine compounds and bioactive substances are also described in this review. In conclusion, the evaluated studies indicate that compounds of marine origin emerge as a promising source of bioactive compounds, revealing an important therapeutic potential for the treatment of ND.

As doenças neurodegenerativas (ND) são caracterizadas, especialmente, pela perda progressiva de neurônios, resultando em disfunções neuropsicomotoras. Mesmo apresentando uma alta prevalência, as DN são tratadas com medicamentos que aliviam os sintomas dos pacientes, mas que desenvolvem eventos adversos e ainda não inibem a progressão da doença. Assim, dentro de uma nova perspectiva farmacológica, esta revisão teve como objetivo verificar o potencial terapêutico de compostos naturais de origem marinha frente às DN. Para tal, foi realizada uma revisão integrativa, segundo a metodologia PRISMA que compreendeu etapas como: busca, pré-seleção e inclusão dos artigos. Os resultados descritos revelaram espécies como, Acaudina malpodioides, Holothuria scabra e Xylaria sp., que apresentaram importantes evidências em relação ao Alzheimer, reduzindo a geração de ROS, apresentando efeitos neuroprotetores e reduzindo a concentração de peptídeo Aß. Sobre a doença de Parkinson (PD), outro exemplo de ND, os compostos bioativos da Holothuria scabra e da Xylaria sp., mostraram ser capazes de diminuir a degeneração de neurônios dopaminérgicos, reduzir a deposição de alfa sinucleína e reduzir a formação de agregados da proteína Huntingtina mutante (Mhtt). Os outros compostos marinhos e substâncias bioativas também são descritos nesta revisão. Em conclusão, os estudos avaliados indicam que os compostos de origem marinha despontam como uma promissora fonte de compostos bioativos, revelando um importante potencial terapêutico para o tratamento das ND.

Physiological gait test: an effective method for analyzing balance, locomotion, and neuromuscular disorders in rats and a comparison to the elevated beam test / Teste de marcha fisiológica: um método eficaz para analisar distúrbios de equilíbrio, locomoção e neuromusculares em roedores

The evaluation of animal locomotor activity is a behavioral tool widely used to measure the mechanisms underlying a particular disease, disorder, or injury, as well as the effects of exposure to a xenobiotic. The elevated beam test is one of the most used tests in rodents to assess balance and motor coordination. Despite being inexpensive and utilizing a simple apparatus, the high beam test requires a long period of animal training and habituation. The development and characterization of an alternative test, namely the gait test, has the potential to circumvent the time and effort required for animal training, deeming it an effective, inexpensive, and fast method for the analysis of behaviors that are comparably assessed by the high beam test. Therefore, the present study focused on determining the effectiveness and feasibility of the gait test for assessing rodent locomotion and balance as a replacement for the elevated beam test. For this purpose, male rats were divided into three groups: one control group exposed to a saline solution (NaCl 0.9%) and two experimental groups exposed to a single dose of either 0.2 or 1.0 mg/kg of ivermectin intraperitoneally for induction of locomotor disturbance. The high beam and gait tests were performed 15 min and 24 h after drug administration. Results show that the experimental groups had difficulty performing the tasks of either test at both time points analyzed compared to the control groups. At the high beam, experimental animals had trouble maintaining balance and walking. At the gait test, experimental animals showed alterations in gait, which were quantitated by: (a) shortening of step length, (b) decrease of stride, (c) altered step symmetry, and (d) altered stride area. Such results are indicative of compensatory efforts and were comparable between both tests. Altogether, the data indicate that the gait test meets all requirements for assessing motor coordination in rodents. The gait test is therefore validated as a complement to the elevated beam test for the study and analysis of neurodegenerative impairment and other disorders involving neuromuscular disturbances.(AU)

A avaliação da atividade locomotora animal é uma ferramenta comportamental bastante utilizada para mensurar os mecanismos subjacentes a uma determinada doença, distúrbio ou lesão e efeitos da exposição a um xenobiótico. Um dos testes mais utilizados em roedores para avaliar o equilíbrio e coordenação motora é o teste da trave elevada que, apesar de ser um teste barato e que exige um aparato simples, é necessário um longo período de treino e habituação dos animais. O desenvolvimento e caracterização de um teste alternativo, chamado de teste da marcha, tem o potencial de contornar o tempo e o esforço necessários ao treino dos animais, considerando-o um método eficaz, barato e rápido para a análise de comportamentos avaliados comparativamente pelo alto teste de feixe. Portanto, o presente estudo concentrou-se em determinar a eficácia e viabilidade do teste de marcha para avaliação da locomoção e equilíbrio de roedores em substituição ao teste da trave elevada. Para isso, ratos machos foram divididos em 3 grupos, sendo 1 grupo controle exposto à solução salina (NaCl 0,9%) e 2 grupos experimentais expostos à dose única de 0,2 e 1,0 mg/kg de ivermectina por via intraperitoneal para indução da alteração locomotora. Os testes de trave elevada e marcha foram realizados 15 min e 24 h após a administração da droga. Os resultados mostram que os grupos experimentais tiveram dificuldade em realizar as tarefas de qualquer teste em ambos os momentos analisados em comparação com os grupos de controle. Na trave elevada, os animais experimentais tiveram dificuldade em manter o equilíbrio e andar. No teste de marcha, os animais experimentais apresentaram alterações na marcha, que foram quantificadas por: (a) encurtamento do comprimento da passada, (b) diminuição da passada, (c) alteração da simetria da passada e (d) alteração da área da passada. Tais resultados são indicativos de esforços compensatórios e foram comparáveis entre os dois testes. Em conjunto, os dados indicam que o teste de marcha atende a todos os requisitos para avaliação da coordenação motora em roedores. O teste de marcha é, portanto, validado como um complementar para o teste da trave elevada e para o estudo e análise de comprometimento neurodegenerativo e outros distúrbios envolvendo distúrbios neuromusculares.(AU)

Comparative analysis of PRNP 12-bp and 23-bp indels in healthy Aberdeen Angus, Aberdeen Angus x Hereford, Holstein Friesian and Uruguayan Creole cattle / Análise comparativa de PRNP 12bp e 23bp indels em bovinos Aberdeen Angus, Aberdeen Angus x Hereford, Holstein Friesian e Crioulo Uruguaio saudáveis

Bovine spongiform encephalopathy (BSE) is a transmissible progressive neurodegenerative disease characterized by the accumulation of a pathological isoform (PrpSC) of the cellular prion protein (PrpC) in the brain of cattle. Two insertion/deletion polymorphisms in the PRNP gene (23bp in the promoter and 12bp in intron 1) have been associated with resistance or susceptibility to the disease. The aim of this study was to analyze the distribution of these polymorphisms in 214 healthy bovines belonging to four different breed groups (Aberdeen Angus, Aberdeen Angus x Hereford, Holstein Friesian and Uruguayan Creole cattle). DNA samples were amplified by end-point PCR. A high frequency of the alleles and haplotype associated with susceptibility to BSE (del12 and del23, and del12-del23, respectively) were found in the Aberdeen Angus, Aberdeen Angus x Hereford and Holstein Friesian animals. At the same time, the Uruguayan Creole cattle presented a higher frequency of the alleles and haplotype associated with resistance to BSE (ins12 and ins23, and ins12-ins23, respectively). These data could indicate a greater genetic resistance of the Uruguayan Creole cattle to BSE compared to other analyzed breeds, reinforcing its value as a zoogenetic resource.

A encefalopatia espongiforme bovina (EEB) é uma doença neurodegenerativa progressiva transmissível dos bovinos, caracterizada pelo acúmulo no cérebro de uma isoforma patológica (PrpSC) da proteína priônica celular (PrpC). Dois polimorfismos de inserção/deleção no gene PRNP (23bp no promotor e 12bp no íntron 1) foram associados à resistência ou suscetibilidade à doença. O objetivo deste trabalho foi analisar a distribuição desses polimorfismos em 214 bovinos sadios, pertencentes a quatro diferentes grupos raciais (Aberdeen Angus, Aberdeen Angus x Hereford, Holstein Friesian e Crioulo Uruguaio). As amostras de DNA foram amplificadas por PCR de tempo final. Uma alta frequência dos alelos e haplótipos associados à suscetibilidade à BSE (del12 e del23 e del12-del23, respectivamente) foram encontrados nos animais Aberdeen Angus, Aberdeen Angus x Hereford e Holstein Friesian, enquanto o gado Crioulo Uruguaio apresentou maior frequência dos alelos e haplótipos associados à resistência à BSE (ins12 e ins23 e ins12-ins23, respectivamente). Esses dados podem indicar uma maior resistência genética do gado Crioulo Uruguaio à BSE em comparação com as outras raças analisadas, reforçando seu valor como recurso zoogenético.

Neuroactive venom compounds obtained from Phlogiellus bundokalbo as potential leads for neurodegenerative diseases: insights on their acetylcholinesterase and beta-secretase inhibitory activities in vitro

Spider venom is a rich cocktail of neuroactive compounds designed to prey capture and defense against predators that act on neuronal membrane proteins, in particular, acetylcholinesterases (AChE) that regulate synaptic transmission through acetylcholine (ACh) hydrolysis - an excitatory neurotransmitter - and beta-secretases (BACE) that primarily cleave amyloid precursor proteins (APP), which are, in turn, relevant in the structural integrity of neurons. The present study provides preliminary evidence on the therapeutic potential of Phlogiellus bundokalbo venom against neurodegenerative diseases. Methods Spider venom was extracted by electrostimulation and fractionated by reverse-phase high-performance liquid chromatography (RP-HPLC) and characterized by matrix-assisted laser desorption ionization-time flight mass spectrometry (MALDI-TOF-MS). Neuroactivity of the whole venom was observed by a neurobehavioral response from Terebrio molitor larvae in vivo and fractions were screened for their inhibitory activities against AChE and BACE in vitro. Results The whole venom from P. bundokalbo demonstrated neuroactivity by inducing excitatory movements from T. molitor for 15 min. Sixteen fractions collected produced diverse mass fragments from MALDI-TOF-MS ranging from 900-4500 Da. Eleven of sixteen fractions demonstrated AChE inhibitory activities with 14.34% (± 2.60e-4) to 62.05% (± 6.40e-5) compared with donepezil which has 86.34% (± 3.90e-5) inhibition (p > 0.05), while none of the fractions were observed to exhibit BACE inhibition. Furthermore, three potent fractions against AChE, F1, F3, and F16 displayed competitive and uncompetitive inhibitions compared to donepezil as the positive control. Conclusion The venom of P. bundokalbo contains compounds that demonstrate neuroactivity and anti-AChE activities in vitro, which could comprise possible therapeutic leads for the development of cholinergic compounds against neurological diseases.(AU)

Neuroactive venom compounds obtained from Phlogiellus bundokalbo as potential leads for neurodegenerative diseases: insights on their acetylcholinesterase and beta-secretase inhibitory activities in vitro

Spider venom is a rich cocktail of neuroactive compounds designed to prey capture and defense against predators that act on neuronal membrane proteins, in particular, acetylcholinesterases (AChE) that regulate synaptic transmission through acetylcholine (ACh) hydrolysis - an excitatory neurotransmitter - and beta-secretases (BACE) that primarily cleave amyloid precursor proteins (APP), which are, in turn, relevant in the structural integrity of neurons. The present study provides preliminary evidence on the therapeutic potential of Phlogiellus bundokalbo venom against neurodegenerative diseases. Methods Spider venom was extracted by electrostimulation and fractionated by reverse-phase high-performance liquid chromatography (RP-HPLC) and characterized by matrix-assisted laser desorption ionization-time flight mass spectrometry (MALDI-TOF-MS). Neuroactivity of the whole venom was observed by a neurobehavioral response from Terebrio molitor larvae in vivo and fractions were screened for their inhibitory activities against AChE and BACE in vitro. Results The whole venom from P. bundokalbo demonstrated neuroactivity by inducing excitatory movements from T. molitor for 15 min. Sixteen fractions collected produced diverse mass fragments from MALDI-TOF-MS ranging from 900-4500 Da. Eleven of sixteen fractions demonstrated AChE inhibitory activities with 14.34% (± 2.60e-4) to 62.05% (± 6.40e-5) compared with donepezil which has 86.34% (± 3.90e-5) inhibition (p > 0.05), while none of the fractions were observed to exhibit BACE inhibition. Furthermore, three potent fractions against AChE, F1, F3, and F16 displayed competitive and uncompetitive inhibitions compared to donepezil as the positive control. Conclusion The venom of P. bundokalbo contains compounds that demonstrate neuroactivity and anti-AChE activities in vitro, which could comprise possible therapeutic leads for the development of cholinergic compounds against neurological diseases.(AU)

Conduta diagnóstica em equino da raça Crioula com síndrome de Cushing / Diagnostic process in a crioulo horse with Cushing’s syndrome

Background: Equine pituitary pars intermedia dysfunction, also known as equine Cushing’s syndrome, is a neurodegenerative disease. An important risk factor for Cushing’s is advanced aging and it is the most common endocrine disorder inolder horses. The prevalence in horses aged over 10 and 15 years is reported as 9.3% and 21%, respectively. Due to the slowprogressive nature of the disease, seasonal variation in hormone output and overlapping endocrine response to other events,accurate diagnosis is challenging. The diagnosis requires the combination of anamnesis, clinical signs, in addition to laboratory tests results. This study aimed to report Cushing’s syndrome in a Crioulo breed horse focusing on diagnostic methods.Case: A 13-year-old male Crioulo breed, orchiectomized, was attended at the Universidade de Passo Fundo (UPF), in PassoFundo, RS, Brazil. The owner reported that the animal had progressive weight loss and coat abnormal growth, with curlyappearance. From visual inspection, body condition score was 4 (1-9) bulging abdomen was noticed, hirsutism, depressionand lethargy. Also, there was a large neoplastic mass on the left side of gluteal region. Later, this mass was classified inhistopathological examination as a fibroblastic sarcoid and was treated. The animal presented physical parameters withinthe physiological limits of the specie. Normochromic normocytic anemia and neutrophilic leukocytosis were reported in thehematologic evaluation. In coproparasitological examination, there were 300 eggs per gram of feaces. Hyperadrenocorticismwas suspected in the clinical examination and dexamethasone suppression test was performed to confirm the fact. Basal serumwas collected at 17 h (M0) and subsequently 40 µg/kg of dexamethasone was administered intramuscular...

Conduta diagnóstica em equino da raça Crioula com síndrome de Cushing / Diagnostic process in a crioulo horse with Cushings syndrome

Background: Equine pituitary pars intermedia dysfunction, also known as equine Cushings syndrome, is a neurodegenerative disease. An important risk factor for Cushings is advanced aging and it is the most common endocrine disorder inolder horses. The prevalence in horses aged over 10 and 15 years is reported as 9.3% and 21%, respectively. Due to the slowprogressive nature of the disease, seasonal variation in hormone output and overlapping endocrine response to other events,accurate diagnosis is challenging. The diagnosis requires the combination of anamnesis, clinical signs, in addition to laboratory tests results. This study aimed to report Cushings syndrome in a Crioulo breed horse focusing on diagnostic methods.Case: A 13-year-old male Crioulo breed, orchiectomized, was attended at the Universidade de Passo Fundo (UPF), in PassoFundo, RS, Brazil. The owner reported that the animal had progressive weight loss and coat abnormal growth, with curlyappearance. From visual inspection, body condition score was 4 (1-9) bulging abdomen was noticed, hirsutism, depressionand lethargy. Also, there was a large neoplastic mass on the left side of gluteal region. Later, this mass was classified inhistopathological examination as a fibroblastic sarcoid and was treated. The animal presented physical parameters withinthe physiological limits of the specie. Normochromic normocytic anemia and neutrophilic leukocytosis were reported in thehematologic evaluation. In coproparasitological examination, there were 300 eggs per gram of feaces. Hyperadrenocorticismwas suspected in the clinical examination and dexamethasone suppression test was performed to confirm the fact. Basal serumwas collected at 17 h (M0) and subsequently 40 µg/kg of dexamethasone was administered intramuscular...(AU)

Achados clínicos, histopatológicos e moleculares da mielopatia degenerativa canina: relato de caso / Clinical, histopathological and molecular findings of canine degenerative myelopathy: case report

Objetivou-se descrever os achados clínicos, histopatológicos e moleculares associados à MDC em um cão da raça Pastor-Suiço. O cão possuía uma paraparesia progressiva em membros pélvicos e foi submetido a avaliações clínicas, pelas quais se obteve, entre outros diferenciais, o diagnóstico presuntivo de MDC. Com a evolução dos sinais, o tutor optou pela eutanásia. Os achados histopatológicos da medula espinhal foram compatíveis com uma degeneração segmentar axonal e mielínica. O diagnóstico molecular foi realizado por meio da extração do DNA obtido por swab oral. Uma PCR foi otimizada utilizando-se primers descritos em literatura para amplificar a região do gene SOD1. A amostra foi, então, submetida a sequenciamento unidirecional, que revelou que o animal em questão era homozigoto para o alelo A para a mutação c.118G>A no éxon 2 do gene SOD1. O diagnóstico clínico presuntivo da MDC no presente caso foi esclarecido por meio dos achados histopatológicos, associados aos achados clínicos, e da sua caracterização molecular. Ressalta-se a contribuição deste relato, que traz aspectos clínicos, histopatológicos e moleculares associados à MDC na raça Pastor-Suíço, para a qual, até o presente momento, na literatura consultada, não há relato dessa enfermidade.(AU)

The objective of this study was to describe the clinical, histopathological and molecular findings associated with MDC in a Swiss Shepherd dog. The dog had a progressive paraparesis in pelvic limbs and was submitted to clinical evaluations where, among other differentials, the presumptive diagnosis of MDC was obtained. With the progression of the nervous deficits tutor opted for euthanasia. The histopathological findings of the spinal cord were compatible with axonal and myelinic segmental degeneration. Molecular diagnosis was performed by extracting the DNA obtained by oral swab. PCR was optimized using primers described in the literature to amplify the SOD1 gene region. The sample was then subjected to one-way sequencing which revealed that the animal in question was homozygous for the A allele for the c.118G>A mutation in exon 2 of the SOD1 gene. The presumptive diagnosis of MDC in the present case was clarified by histopathological findings, as well as by its molecular characterization. The contribution of this report brings clinical, histopathological and molecular aspects associated with canine degenerative myelopathy in the Swiss Shepherd breed, that until this moment, in the literature consulted, there is no report of this disease in the breed mentioned.(AU)

Achados clínicos, histopatológicos e moleculares da mielopatia degenerativa canina: relato de caso / Clinical, histopathological and molecular findings of canine degenerative myelopathy: case report

Objetivou-se descrever os achados clínicos, histopatológicos e moleculares associados à MDC em um cão da raça Pastor-Suiço. O cão possuía uma paraparesia progressiva em membros pélvicos e foi submetido a avaliações clínicas, pelas quais se obteve, entre outros diferenciais, o diagnóstico presuntivo de MDC. Com a evolução dos sinais, o tutor optou pela eutanásia. Os achados histopatológicos da medula espinhal foram compatíveis com uma degeneração segmentar axonal e mielínica. O diagnóstico molecular foi realizado por meio da extração do DNA obtido por swab oral. Uma PCR foi otimizada utilizando-se primers descritos em literatura para amplificar a região do gene SOD1. A amostra foi, então, submetida a sequenciamento unidirecional, que revelou que o animal em questão era homozigoto para o alelo A para a mutação c.118G>A no éxon 2 do gene SOD1. O diagnóstico clínico presuntivo da MDC no presente caso foi esclarecido por meio dos achados histopatológicos, associados aos achados clínicos, e da sua caracterização molecular. Ressalta-se a contribuição deste relato, que traz aspectos clínicos, histopatológicos e moleculares associados à MDC na raça Pastor-Suíço, para a qual, até o presente momento, na literatura consultada, não há relato dessa enfermidade.(AU)

The objective of this study was to describe the clinical, histopathological and molecular findings associated with MDC in a Swiss Shepherd dog. The dog had a progressive paraparesis in pelvic limbs and was submitted to clinical evaluations where, among other differentials, the presumptive diagnosis of MDC was obtained. With the progression of the nervous deficits tutor opted for euthanasia. The histopathological findings of the spinal cord were compatible with axonal and myelinic segmental degeneration. Molecular diagnosis was performed by extracting the DNA obtained by oral swab. PCR was optimized using primers described in the literature to amplify the SOD1 gene region. The sample was then subjected to one-way sequencing which revealed that the animal in question was homozygous for the A allele for the c.118G>A mutation in exon 2 of the SOD1 gene. The presumptive diagnosis of MDC in the present case was clarified by histopathological findings, as well as by its molecular characterization. The contribution of this report brings clinical, histopathological and molecular aspects associated with canine degenerative myelopathy in the Swiss Shepherd breed, that until this moment, in the literature consulted, there is no report of this disease in the breed mentioned.(AU)

Spongiform leukoencephalopathy in an adult mixed breed female dog

Leukoencephalomyelopathy is a nonspecific lesion characterized by widespread vacuolation of central nervous system white matter. It is mainly of genetic basis, occurring in young pure breed dogs. This report describes a neurodegenerative disease associated to demyelination in an adult mixed breed female dog. After 20 days in a kennel with12 other dogs, the dog showed progressive nervous signs with ataxia and inability to maintain balance. No other dog was affected. After 15 days, the animal was euthanized in extremis and necropsied. No macroscopic lesions of diagnostic relevance were present. Microscopically, status espongiosus was observed in white matter throughout the length of theneuroaxis, from frontal brain lobe to lumbar spinal cord. Specific stains of Kluver Barrera and immunohistochemistry for the detection of phosphorylated and non-phosphorylated neurofilaments, microglia, astrocytosis, oligodendrocytosis and myelin proteins in brain and spinal cord sections showed demyelination, axonal fragmentation and degeneration, microgliosis and decrease of oligodendrocytes. The anatomopathological study and epidemiological data suggests a primary demyelination due to decrease in number and function of oligodendrocytes, which is probably of genetic basis with lateonset.

Neurobehavioral and neuroprotector effects of caffeine in animal models

This review aims to analyze and contrast the neurological effects associated with the use of caffeine on neurobehavior and neuroprotection in animal models. Caffeine belongs to the group of methylxanthines that exert a direct effect on adenosine receptors associated with inhibitory or excitatory G proteins, generating modification of cyclic AMP activity and intracellular calcium flow which produces alterations in the modulation system of the neurotransmitters dopamine and glutamate. The regulation of the neurotransmission systems generates protection against the inflammation of the central nervous system, by activation of the microglia and reinforcement of the blood-brain barrier. This drug will also restore cognition or prevent memory loss in Parkinson's or Alzheimer's diseases. It is important to establish new study models in other species to assess whether the behavior of the molecule is similar and to obtain other clinical applications in its behavioral and neuroprotective effects.(AU)

Neurobehavioral and neuroprotector effects of caffeine in animal models

This review aims to analyze and contrast the neurological effects associated with the use of caffeine on neurobehavior and neuroprotection in animal models. Caffeine belongs to the group of methylxanthines that exert a direct effect on adenosine receptors associated with inhibitory or excitatory G proteins, generating modification of cyclic AMP activity and intracellular calcium flow which produces alterations in the modulation system of the neurotransmitters dopamine and glutamate. The regulation of the neurotransmission systems generates protection against the inflammation of the central nervous system, by activation of the microglia and reinforcement of the blood-brain barrier. This drug will also restore cognition or prevent memory loss in Parkinson's or Alzheimer's diseases. It is important to establish new study models in other species to assess whether the behavior of the molecule is similar and to obtain other clinical applications in its behavioral and neuroprotective effects.

Spongiform leukoencephalopathy in an adult mixed breed female dog

Leukoencephalomyelopathy is a nonspecific lesion characterized by widespread vacuolation of central nervous system white matter. It is mainly of genetic basis, occurring in young pure breed dogs. This report describes a neurodegenerative disease associated to demyelination in an adult mixed breed female dog. After 20 days in a kennel with12 other dogs, the dog showed progressive nervous signs with ataxia and inability to maintain balance. No other dog was affected. After 15 days, the animal was euthanized in extremis and necropsied. No macroscopic lesions of diagnostic relevance were present. Microscopically, status espongiosus was observed in white matter throughout the length of theneuroaxis, from frontal brain lobe to lumbar spinal cord. Specific stains of Kluver Barrera and immunohistochemistry for the detection of phosphorylated and non-phosphorylated neurofilaments, microglia, astrocytosis, oligodendrocytosis and myelin proteins in brain and spinal cord sections showed demyelination, axonal fragmentation and degeneration, microgliosis and decrease of oligodendrocytes. The anatomopathological study and epidemiological data suggests a primary demyelination due to decrease in number and function of oligodendrocytes, which is probably of genetic basis with lateonset.(AU)

Dalbergia ecastaphyllum leaf extracts: in vitro inhibitory potential against enzymes related to metabolic syndrome, inflammation and neurodegenerative diseases

For the first time, the anti-hemolytic activity and the enzyme inhibitory activities of Dalbergia ecastaphyllum leaves extracts were tested against α-amylase, α-glucosidase, lipase, acetylcholinesterase, butyrylcholinesterase, tyrosinase and hyaluronidase. The phenolic profile of the obtained extracts was also investigated by high-performance liquid chromatography with photodiode array detection (HPLC-PAD). The extracts showed inhibitory activity against all enzymes evaluated, with the highest inhibitory activity reported for the enzyme hyaluronidase (28.28 ± 2.43 to 72.19 ± 1.40 μg mL-1). The obtained extracts also demonstrate anti-hemolytic activity (52.22 ± 1.62 to 71.17 ± 1.82%). Among the phenolic compounds identified, protocatechuic, vanillic and β-resorcylic acids were the most abundant (1.13 ± 0.06 to 2.53 ± 0.06, 0.90 ± 0.06 to 2.19 ± 0.06 and 1.03 ± 1.62 to 22.11 ± 1.62 mg L-1, respectively). In the statistical analysis, a significant correlation was found between the flavonoids content and all enzymes inhibitory activities. The present study showed that D. ecastaphyllum leaves extracts may have the potential to be used in the therapeutic treatment of several diseases such as Alzheimer, Parkinson, type 2 diabetes mellitus, hyperglycemia, and pigmentation, as well as those associated with oxidative stress.

Uso de modelos animais no estudo de doenças neurológicas / Use of animal models for the study of neurological diseases

A expectativa de vida aumentou consideravelmente no século XX. Este fato é consequência da queda das taxas de mortalidade em função não só dos avanços da pesquisa e da medicina, mas também da melhoria nas condições gerais de vida. Com isso, houve um aumento na incidência de doenças ligadas ao envelhecimento, como por exemplo, as demências degenerativas, consideradas atualmente um dos principais problemas de saúde pública pois são em sua maioria incuráveis. Nesse sentido, há uma necessidade urgente de desenvolver novas estratégias terapêuticas para combater tais doenças. Modelos animais provaram ser uma ferramenta útil para auxiliar a pesquisa, pois reproduzem diferentes aspectos da doença que não podem ser analisados em seres humanos. Desta forma, eles contribuem para o conhecimento sobre a fisiopatologia e causas das enfermidades neurológicas, permitindo com que a comunidade científica entenda quais os mecanismos que podem iniciar e desenvolver a perda de função neural, fornecendo assim terapias promissoras para o tratamento. Neste artigo de revisão, nós descrevemos alguns dos modelos animais utilizados no estudo das principais doenças que acometem o sistema nervoso.

Life expectancy increased considerably in the 20th century. This is consequence of the decrease in mortality rates due not only to advances in research and medicine, but also to improvements in general life conditions. As a result, there has been an increase in the incidence of diseases associated to aging, such as degenerative dementias, which are currently considered one of the main public health problems due to the lack of effective treatments. In this sense, there is an urgent need to develop new therapeutic strategies to combat such diseases. Animal models have proved to be a useful tool to research as they reproduce different aspects of the disease that cannot be analyzed in humans. In this way, they contribute to the knowledge about the pathophysiology and causes of neurological diseases, allowing the scientific community to understand the mechanisms that can initiate and develop the loss of neural function, providing promising new therapies. In this review article, we describe some of the animal models used in the study of the major diseases that affect the nervous system.

Uso de modelos animais no estudo de doenças neurológicas / Use of animal models for the study of neurological diseases

A expectativa de vida aumentou consideravelmente no século XX. Este fato é consequência da queda das taxas de mortalidade em função não só dos avanços da pesquisa e da medicina, mas também da melhoria nas condições gerais de vida. Com isso, houve um aumento na incidência de doenças ligadas ao envelhecimento, como por exemplo, as demências degenerativas, consideradas atualmente um dos principais problemas de saúde pública pois são em sua maioria incuráveis. Nesse sentido, há uma necessidade urgente de desenvolver novas estratégias terapêuticas para combater tais doenças. Modelos animais provaram ser uma ferramenta útil para auxiliar a pesquisa, pois reproduzem diferentes aspectos da doença que não podem ser analisados em seres humanos. Desta forma, eles contribuem para o conhecimento sobre a fisiopatologia e causas das enfermidades neurológicas, permitindo com que a comunidade científica entenda quais os mecanismos que podem iniciar e desenvolver a perda de função neural, fornecendo assim terapias promissoras para o tratamento. Neste artigo de revisão, nós descrevemos alguns dos modelos animais utilizados no estudo das principais doenças que acometem o sistema nervoso.(AU)

Life expectancy increased considerably in the 20th century. This is consequence of the decrease in mortality rates due not only to advances in research and medicine, but also to improvements in general life conditions. As a result, there has been an increase in the incidence of diseases associated to aging, such as degenerative dementias, which are currently considered one of the main public health problems due to the lack of effective treatments. In this sense, there is an urgent need to develop new therapeutic strategies to combat such diseases. Animal models have proved to be a useful tool to research as they reproduce different aspects of the disease that cannot be analyzed in humans. In this way, they contribute to the knowledge about the pathophysiology and causes of neurological diseases, allowing the scientific community to understand the mechanisms that can initiate and develop the loss of neural function, providing promising new therapies. In this review article, we describe some of the animal models used in the study of the major diseases that affect the nervous system.(AU)

Efeitos da hipercolesterolemia sobre as desordens neurológicas associadas à integridade do hipocampo / Effects of hyperercolesterolemia on neurological disorders associated with the integrity of hypocampus

O colesterol é um componente lipofílico essencial para o organismo, devido a suas diversas funcionalidades, como participação na síntese de vitamina D, metabolismo de hormônios esteroides e sexuais, auxilia na absorção de vitaminas lipossolúveis;além disso, participa da manutenção da fluidez e da permeabilidade da membrana plasmática. Esta função é extremamente importante, para regularizar o potencial de ação e consequente plasticidade sináptica. No entanto, níveis elevados de colesterol, decorrente de uma dieta hiperlipidêmica, ou devido a uma disfunção genética está relacionado com diversas patologias cardiovasculares e metabólicas, como Diabetes. Além disso, altos níveis de colesterol participam da fisiopatologia de neuropatias, como Azheimer e Parkinson. Levando em consideração que algumas neuropatias possuem como um dos eventos as alterações hipocampais, este trabalho objetivou investigar, através de revisão da literatura, utilizando ensaios pré-clínicos, a possível relação entre a hipercolesterolemia, o hipocampo e a fisiopatologia de desordens neurológicas. Buscou-se informações em fevereiro de 2018, nas bases de dados Pubmed e Lilacs, utilizando-se os descritores: “hypercholesterolemia” e “hippocampus”. Utilizou-se como critérios de inclusão: trabalhos pré-clínicos (entre 2013 e 2017) em idioma inglês. Foram critério de exclusão: artigos de revisão, sem haver uma relação com a hipercolesterolemia e as desordens neurológicase o hipocampo.O aumento de colesterol sérico foi associado, tanto às alterações bioquímicas,destacando-se estresse oxidativo, inflamação e metabolismo da proteína amiloide, quanto aos processos neurodegenerativ os a nível hipocampal. Além disto, foi observado que fármacos que modulam os níveis de colesterol sérico também influenciaram a cognição e a integridade hipocampal.

Cholesterol is a lipophilic component essential for the body due to its diverse functionalities, such as participation in vitamin D synthesis, metabolism of steroids and sex hormones, help in the absorption of fat soluble vitamins, besides participating in the maintenance of the fluidity and permeability of plasma membrane. This function is extremely important to regularize the action potential and the consequent synaptic plasticity. However, high cholesterol levels due to a hyperlipidemic diet or genetic dysfunction are related to various cardiovascular and metabolic pathologies, such as diabetes. In addition, elevated cholesterol levels participate in the pathophysiology of neuropathies, such as Azheimer and Parkinson. Considering that some neuropathies have hippocampal alterations as one of the events, this study aimed to investigate the possible relationship between hypercholesterolemia, hippocampus and the pathophysiology of neurological disorders through a review of theliterature using preclinical studies. During the month of February 2018, we searched the databases Pubmed and Lilacs, using "hypercholesterolemia" and "hippocampus". Inclusion criteria: Preclinical studies published between 2013 and 2017 were selected. Exclusion criteria: review articles, articles that did not correlate hypercholesterolemia with neurological disorders and hippocampus. Increased serum cholesterol was associated with biochemical changes, especially oxidative stress, inflammation and metabolism of the amyloid protein, as well as neurodegenerative processes at the hippocampus level. In addition, drugs that modulate serum cholesterol levels have also been found to influence cognition and hippocampal integrity. Preclinical studies indicate that the hippocampus was susceptible to hypercholesterolemia. Therefore, hypercholesterolemia may contribute to neurological disorders with hippocampal disorders.

Efeitos da hipercolesterolemia sobre as desordens neurológicas associadas à integridade do hipocampo / Effects of hyperercolesterolemia on neurological disorders associated with the integrity of hypocampus

O colesterol é um componente lipofílico essencial para o organismo, devido a suas diversas funcionalidades, como participação na síntese de vitamina D, metabolismo de hormônios esteroides e sexuais, auxilia na absorção de vitaminas lipossolúveis;além disso, participa da manutenção da fluidez e da permeabilidade da membrana plasmática. Esta função é extremamente importante, para regularizar o potencial de ação e consequente plasticidade sináptica. No entanto, níveis elevados de colesterol, decorrente de uma dieta hiperlipidêmica, ou devido a uma disfunção genética está relacionado com diversas patologias cardiovasculares e metabólicas, como Diabetes. Além disso, altos níveis de colesterol participam da fisiopatologia de neuropatias, como Azheimer e Parkinson. Levando em consideração que algumas neuropatias possuem como um dos eventos as alterações hipocampais, este trabalho objetivou investigar, através de revisão da literatura, utilizando ensaios pré-clínicos, a possível relação entre a hipercolesterolemia, o hipocampo e a fisiopatologia de desordens neurológicas. Buscou-se informações em fevereiro de 2018, nas bases de dados Pubmed e Lilacs, utilizando-se os descritores: “hypercholesterolemia” e “hippocampus”. Utilizou-se como critérios de inclusão: trabalhos pré-clínicos (entre 2013 e 2017) em idioma inglês. Foram critério de exclusão: artigos de revisão, sem haver uma relação com a hipercolesterolemia e as desordens neurológicase o hipocampo.O aumento de colesterol sérico foi associado, tanto às alterações bioquímicas,destacando-se estresse oxidativo, inflamação e metabolismo da proteína amiloide, quanto aos processos neurodegenerativ os a nível hipocampal. Além disto, foi observado que fármacos que modulam os níveis de colesterol sérico também influenciaram a cognição e a integridade hipocampal.(AU)

Cholesterol is a lipophilic component essential for the body due to its diverse functionalities, such as participation in vitamin D synthesis, metabolism of steroids and sex hormones, help in the absorption of fat soluble vitamins, besides participating in the maintenance of the fluidity and permeability of plasma membrane. This function is extremely important to regularize the action potential and the consequent synaptic plasticity. However, high cholesterol levels due to a hyperlipidemic diet or genetic dysfunction are related to various cardiovascular and metabolic pathologies, such as diabetes. In addition, elevated cholesterol levels participate in the pathophysiology of neuropathies, such as Azheimer and Parkinson. Considering that some neuropathies have hippocampal alterations as one of the events, this study aimed to investigate the possible relationship between hypercholesterolemia, hippocampus and the pathophysiology of neurological disorders through a review of theliterature using preclinical studies. During the month of February 2018, we searched the databases Pubmed and Lilacs, using "hypercholesterolemia" and "hippocampus". Inclusion criteria: Preclinical studies published between 2013 and 2017 were selected. Exclusion criteria: review articles, articles that did not correlate hypercholesterolemia with neurological disorders and hippocampus. Increased serum cholesterol was associated with biochemical changes, especially oxidative stress, inflammation and metabolism of the amyloid protein, as well as neurodegenerative processes at the hippocampus level. In addition, drugs that modulate serum cholesterol levels have also been found to influence cognition and hippocampal integrity. Preclinical studies indicate that the hippocampus was susceptible to hypercholesterolemia. Therefore, hypercholesterolemia may contribute to neurological disorders with hippocampal disorders.(AU)

X-ray dynamic observation of cervical degenerative disease induced by unbalanced dynamic and static forces in rats

Purpose: To investigate dynamically the X-ray appearance of cervical degenerative disease induced by unbalanced dynamic and static forces in rats. Methods: A total of 60 Sprague Dawley rats were randomized into test (n=45) and control (n=15) groups, which were randomly subdivided into the one-, three- and six-month post-operative groups. The test group included 10, 15 and 20 rats at the respective corresponding post-operative stage and the control group included five rats at each time-point. By excising cervicodorsal muscles, interspinous ligaments and supraspinous ligament of rats in the test group, the balance of dynamic and static forces on cervical vertebrae was disrupted to establish a rat model of cervical degeneration. Spinal X-ray images were acquired, and intervertebral disc space and intervertebral foramen size were measured at one, three and six months post-operation. The results were analyzed and compared among groups. Results: Cervical dynamic and static imbalance accelerated the appearance of cervical degenerative disease on X-ray. Conclusion: Cervical degenerative disease may be induced by unbalanced dynamic and static forces in rats.(AU)