Assuntos
Colo/irrigação sanguínea , Neoplasias do Colo/cirurgia , Ligadura/métodos , Artéria Mesentérica Inferior/cirurgia , Tomografia Computadorizada Multidetectores/estatística & dados numéricos , Neoplasias Retais/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Colo/diagnóstico por imagem , Neoplasias do Colo/diagnóstico por imagem , Feminino , Humanos , Masculino , Artéria Mesentérica Inferior/diagnóstico por imagem , Pessoa de Meia-Idade , Neoplasias Retais/diagnóstico por imagem , Reprodutibilidade dos Testes , Estudos RetrospectivosRESUMO
INTRODUCTION: Spasticity is the most difficult motor disorder to be treated after an encephalic vascular accident or stroke, which interferes in the patient's selective motor functioning. AIM: To compare the involvement type of the extrinsic muscles, the functionality degree of the hand and functional independence of patients with spastic hemiplegia due to stroke after botulinum toxin A (BTA) infiltration. They were divided into a group receiving occupational therapy treatment (group I), and other who has not received it (group II). PATIENTS AND METHODS: Longitudinal study with 20 spastic hemiplegic outpatients due to stroke, both sexes, with average age of 53.1 +/- 15.3 years-old who have been attending in the botulinum toxin service. They have received BTA infiltration in the muscles responsible for the hand functional movements, and they were evaluated before and after 3-months infiltration. To collect data, these instruments were used: anamnesis questionnaire of occupational therapy, the Classification of involvement types of extrinsic muscle, according to adapted Zancolli, the adapted Hausen's Functional Classification, the Functional Independence Measure Scale, the Rivermead's Scale of Activity of Daily Life and the Barthel Index. RESULTS: In the classification, according to adapted Zancolli, group I presented higher improvement of involvement than group II. Statistical significance (p < 0.05) was observed in group I according to the other evaluations, except in the Barthel Index. CONCLUSION: Both effectiveness and importance of occupational therapy were observed in the rehabilitation of patients with spastic hemiplegia due to stroke after infiltration of BTA providing them greater abilities and functional independence in their daily life activities.
Assuntos
Antidiscinéticos/uso terapêutico , Toxinas Botulínicas/uso terapêutico , Mãos/fisiopatologia , Hemiplegia/tratamento farmacológico , Hemiplegia/reabilitação , Terapia Ocupacional , Adulto , Idoso , Feminino , Hemiplegia/etiologia , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/fisiopatologia , Reabilitação do Acidente Vascular CerebralRESUMO
AIM: To examine the level of dependence, the functional class, the most frequent type of compromise and the proprioception of the hand in spastic cerebral palsy following the application of botulinum toxin, as well as to determine the sociodemographic characteristics of the individuals involved. PATIENTS AND METHODS: We conducted a cross-sectional study of 21 spastic patients with extrinsic muscle involvement, of both sexes and a mean age of 15.4 +/- 5.6 years, who attended the neuro-rehabilitation outpatients department and were treated with botulinum toxin in the muscles responsible for the functional movements in the hand; they were evaluated after a mean period of 2.1 years. Patients were subjected to procedures such as a semi-structured interview, the FIM (Functional Independence Measurement) scale, Hausen's functional characterisation, Zancolli classification and a proprioception test. RESULTS: There was a predominance of females (57% of patients) and of a basic level of schooling. On the FIM scale, 38% of the patients presented modified independence, without help; 23.8% belonged to Hausen grade 3 (grasping and holding an object steady with the help of the other hand). On the Zancolli classification, 54% belonged to type III (the fingers can only be extended if the fist is bent more than 70 masculine); perception of movement is absent (76.2%) and the sense of position of the movement is altered (54.2%). CONCLUSIONS: Findings confirmed the existence of a high rate of modified independence, grade 3 (Hausen), together with type III involvement (Zancolli) and alterations affecting proprioception. Data from the study show the importance of occupational therapy as part of the care received by patients with cerebral palsy following the administration of botulinum toxin type A.
Assuntos
Toxinas Botulínicas Tipo A/uso terapêutico , Paralisia Cerebral , Mãos/fisiopatologia , Fármacos Neuromusculares/uso terapêutico , Adolescente , Adulto , Paralisia Cerebral/tratamento farmacológico , Paralisia Cerebral/fisiopatologia , Criança , Estudos Transversais , Feminino , Humanos , Masculino , Movimento/fisiologia , Espasticidade Muscular/tratamento farmacológico , Exame Neurológico , Modalidades de FisioterapiaRESUMO
BACKGROUND: Neurocysticercosis is a major cause of epilepsy in developing countries and is endemic in Brazil. To test the hypothesis that the aetiological profile of patients with intractable epilepsy in Brazil includes neurocysticercosis, we conducted a cross sectional study investigating the aetiology of intractable epilepsy. METHODS: A total of 512 patients evaluated at the outpatient clinic for intractable epilepsy at the Ribeirão Preto School of Medicine were included in the survey. Medical intractability was determined on the basis of seizure incidence and severity, and response to appropriate epilepsy management. Neuroimaging included brain CT with non-contrasted and contrasted phases and high resolution MRI. Patients were divided into neurocysticercosis and non-neurocysticercosis groups according to previous diagnostic criteria. RESULTS: The most common epileptogenic lesions were mesial temporal sclerosis (MTS; 56.0%), malformations of cortical development (12.1%), and brain tumours (9.9%). Neuroimaging was normal in 8.7% of patients. Calcifications were found in 27% of patients and were significantly more common in patients with MTS than in those without MTS (p<0.001). Isolated neurocysticercosis was found in only eight patients (1.56%). CONCLUSIONS: These data suggest that neurocysticercosis is an uncommon cause of intractable epilepsy, even in an endemic region such as Brazil, and that it may only represent a coexistent pathology. However, an analysis of our findings reveals that neurocysticercosis was more common in patients with MTS. This finding could suggest either that there is a cause-effect relationship between MTS and neurocysticercosis, or that MTS and neurocysticercosis co-vary with a missing variable, such as socio-economic status.
Assuntos
Calcinose/complicações , Calcinose/patologia , Epilepsia/etiologia , Neurocisticercose/complicações , Neurocisticercose/patologia , Adolescente , Adulto , Encefalopatias/complicações , Encefalopatias/patologia , Criança , Estudos Transversais , Demografia , Eletroencefalografia , Epilepsia/diagnóstico , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Neurocisticercose/parasitologia , Esclerose/complicações , Esclerose/patologia , Lobo Temporal/patologiaRESUMO
The clinical manifestations of neurocysticercosis (NC) are varied and depend on the number and location of cysts, as well as on the host immune response. Symptoms usually occur in NC when cysticerci enter a degenerative course associated with an inflammatory response. The expression of brain damage markers may be expected to increase during this phase. S100B is a calcium-binding protein produced and released predominantly by astrocytes that has been used as a marker of reactive gliosis and astrocytic death in many pathological conditions. The aim of the present study was to investigate the levels of S100B in patients in different phases of NC evolution. Cerebrospinal fluid and serum S100B concentrations were measured in 25 patients with NC: 14 patients with degenerative cysts (D), 8 patients with viable cysts (V) and 3 patients with inactive cysts. All NC patients, except 1, had five or less cysts. In most of them, symptoms had been present for at least 1 month before sample collection. Samples from 8 normal controls (C) were also assayed. The albumin quotient was used to estimate the blood-brain barrier permeability. There were no significant differences in serum (P = 0.5) or cerebrospinal fluid (P = 0.91) S100B levels among the V, D, and C groups. These findings suggest that parenchymal changes associated with a relatively small number of degenerating cysts probably have a negligible impact on glial tissue.
Assuntos
Fatores de Crescimento Neural/sangue , Fatores de Crescimento Neural/líquido cefalorraquidiano , Neurocisticercose/sangue , Neurocisticercose/líquido cefalorraquidiano , Proteínas S100/sangue , Proteínas S100/líquido cefalorraquidiano , Adolescente , Adulto , Idoso , Animais , Biomarcadores/sangue , Biomarcadores/líquido cefalorraquidiano , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Subunidade beta da Proteína Ligante de Cálcio S100RESUMO
The clinical manifestations of neurocysticercosis (NC) are varied and depend on the number and location of cysts, as well as on the host immune response. Symptoms usually occur in NC when cysticerci enter a degenerative course associated with an inflammatory response. The expression of brain damage markers may be expected to increase during this phase. S100B is a calcium-binding protein produced and released predominantly by astrocytes that has been used as a marker of reactive gliosis and astrocytic death in many pathological conditions. The aim of the present study was to investigate the levels of S100B in patients in different phases of NC evolution. Cerebrospinal fluid and serum S100B concentrations were measured in 25 patients with NC: 14 patients with degenerative cysts (D), 8 patients with viable cysts (V) and 3 patients with inactive cysts. All NC patients, except 1, had five or less cysts. In most of them, symptoms had been present for at least 1 month before sample collection. Samples from 8 normal controls (C) were also assayed. The albumin quotient was used to estimate the blood-brain barrier permeability. There were no significant differences in serum (P = 0.5) or cerebrospinal fluid (P = 0.91) S100B levels among the V, D, and C groups. These findings suggest that parenchymal changes associated with a relatively small number of degenerating cysts probably have a negligible impact on glial tissue.
Assuntos
Humanos , Animais , Masculino , Feminino , Adolescente , Adulto , Pessoa de Meia-Idade , Fatores de Crescimento Neural/sangue , Fatores de Crescimento Neural/classificação , Neurocisticercose/imunologia , /sangue , /classificação , Biomarcadores/sangue , Biomarcadores/líquido cefalorraquidiano , Estudos de Casos e Controles , Neurocisticercose/sangue , Neurocisticercose/classificaçãoRESUMO
OBJECTIVES: Although chronic calcified neurocysticercosis (NCC) has been considered a major cause of symptomatic epilepsy in developing countries, it can also be an incidental pathological finding in epileptic patients from endemic regions. The mechanisms of brain plasticity occurring in patients with NCC during and after the inflammatory process related to the parasite infection, death, degeneration, and calcification within the host brain might be an independent factor for cognitive impairment in patients with NCC and epilepsy. In order to assess this possibility cognitive performance of patients with mesial temporal lobe epilepsy related to hippocampal sclerosis (MTLE-HS) with and without NCC was investigated through structured neuropsychological testing. METHODS: Cognitive performance of long term MTLE-HS patients with (HS-NCC group, n = 32) and without NCC (HS only, n = 48) was compared. Imbalances between the two groups with respect to clinical, demographic, neuroimaging, and electrophysiological variables were adjusted by linear multiple regression analysis and Bonferroni correction for multiple tests. RESULTS AND CONCLUSIONS: There were no cognitive performance differences between HS-NCC and HS only patients, leading to the conclusion that chronic calcified NCC per se does not aggravate the cognitive performance of patients with long term MTLE-HS.
Assuntos
Encefalopatias/patologia , Encefalopatias/parasitologia , Calcinose/complicações , Calcinose/patologia , Transtornos Cognitivos/diagnóstico , Transtornos Cognitivos/etiologia , Epilepsia do Lobo Temporal/etiologia , Neurocisticercose/complicações , Neurocisticercose/patologia , Demografia , Eletroencefalografia , Epilepsia do Lobo Temporal/diagnóstico , Feminino , Cefaleia/diagnóstico , Cefaleia/epidemiologia , Cefaleia/etiologia , Humanos , Angiografia por Ressonância Magnética , Imageamento por Ressonância Magnética , Masculino , Neurocisticercose/líquido cefalorraquidiano , Testes Neuropsicológicos , Estudos Prospectivos , Índice de Gravidade de Doença , Trombose dos Seios Intracranianos/epidemiologia , Trombose dos Seios Intracranianos/etiologiaRESUMO
We report two male patients with medically intractable epilepsy and obsessive-compulsive disorder (OCD) symptoms. Both patients experienced remission of obsessive-compulsive symptoms after surgical treatment of epilepsy. Although the surgeries targeted different brain regions, the two patients had in common unilateral anterior cingulate cortex ablation. On the basis of these observations, we discuss the pathophysiology of OCD symptoms, emphasizing the role of corticosubcortical pathways in their genesis. Our data suggest that surgeries that affect neural loops associated with obsessive-compulsive symptoms can lead to an improvement of OCD; however, the structures responsible for this effect cannot be conclusively determined.
Assuntos
Transtorno da Personalidade Compulsiva/etiologia , Epilepsia/cirurgia , Procedimentos Neurocirúrgicos/efeitos adversos , Complicações Pós-Operatórias/fisiopatologia , Psicocirurgia/métodos , Adulto , Epilepsia/complicações , Epilepsia/patologia , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Resultado do TratamentoRESUMO
Studies in animals lacking the cellular prion protein (PrP(c)) gene (Prnp) showed higher neuronal excitability in vitro and increased sensitivity to seizures in vivo. The authors previously reported a rare polymorphism at codon 171 (Asn-->Ser) of human Prnp to be associated with mesial temporal lobe epilepsy related to hippocampal sclerosis. They demonstrated that the same variant allele is also associated with symptomatic epilepsies related to different forms of malformations of cortical development.
Assuntos
Substituição de Aminoácidos , Amiloide/genética , Córtex Cerebral/anormalidades , Epilepsia/genética , Polimorfismo de Nucleotídeo Único , Precursores de Proteínas/genética , Adolescente , Adulto , Alelos , Apoptose , Brasil/epidemiologia , Divisão Celular , Movimento Celular , Córtex Cerebral/patologia , Criança , Anormalidades Congênitas/epidemiologia , Anormalidades Congênitas/genética , Anormalidades Congênitas/patologia , Análise Mutacional de DNA , Epilepsia/epidemiologia , Epilepsia/patologia , Etnicidade/genética , Europa (Continente)/epidemiologia , Feminino , Frequência do Gene , Genótipo , Humanos , Masculino , Proteínas Priônicas , PríonsRESUMO
BACKGROUND: Mesial temporal lobe epilepsy related to hippocampal sclerosis (MTLE-HS) is the most common surgically remediable epileptic syndrome. Ablation of the cellular prion protein (PrP(c)) gene (PRNP) enhances neuronal excitability of the hippocampus in vitro and sensitivity to seizure in vivo, indicating that PrP(c) might be related to epilepsy. OBJECTIVE: To evaluate the genetic contribution of PRNP to MTLE-HS. METHODS: The PRNP coding sequence of DNA from peripheral blood cells of 100 consecutive patients with surgically treated MTLE-HS was compared to that from a group of healthy controls adjusted for sex, age, and ethnicity (n = 180). The presence of PRNP variant alleles was correlated with clinical and presurgical parameters as well as surgical outcome. RESULTS: A variant allele at position 171 (Asn-->Ser), absent in controls, was found in heterozygosis (Asn171Ser) in 23% of patients (p < 0.0001). The PRNP genotypes were not correlated with any clinical or presurgical data investigated. However, patients carrying the Asn171Ser variant had a five times higher chance of continuing to have seizures after temporal lobectomy (95% CI 1.65 to 17.33, p = 0.005) than those carrying the normal allele. At 18 months after surgery, 91.8% of patients with the normal allele at codon 171 were seizure free, in comparison to 68.2% of those carrying Asn171Ser (p = 0.005). CONCLUSIONS: The PRNP variant allele Asn171Ser is highly prevalent in patients with medically untreatable MTLE-HS and influences their surgical outcome. The results suggest that the PRNP variant allele at codon 171 (Asn171Ser) is associated with epileptogenesis in MTLE-HS.
Assuntos
Epilepsia do Lobo Temporal/fisiopatologia , Epilepsia do Lobo Temporal/cirurgia , Variação Genética/genética , Príons/genética , Esclerose/genética , Adulto , Substituição de Aminoácidos , Química Encefálica , DNA/análise , Intervalo Livre de Doença , Epilepsia do Lobo Temporal/complicações , Etnicidade/estatística & dados numéricos , Feminino , Frequência do Gene , Hipocampo/patologia , Humanos , Imageamento por Ressonância Magnética , Masculino , Razão de Chances , Esclerose/complicações , Esclerose/patologia , Distribuição por Sexo , Resultado do TratamentoRESUMO
OBJECTIVE: To assess whether serum S100B levels could reflect a glial response in patients with epilepsy secondary to neurocysticercosis (NCC) and with idiopathic epilepsy. SUBJECTS AND METHODS: Serum S100B levels were measured using an immunoluminometric assay in 20 patients with focal epilepsy related to chronic NCC (NCC group), and 19 patients with focal epilepsy (EPI group), matched by epidemiological and clinical data. Epileptic patients were compared with 20 healthy controls (CON group) matched by age and sex. RESULTS: No difference was observed in S100B levels among NCC, EPI and CON groups (P>0.39). Serum S100B levels were not affected by antiepileptic drugs, frequency and type of seizures. Preliminarily, significantly higher levels of S100B were observed in patients with bilateral electroencephalographic (EEG) findings than in patients with unilateral and normal EEG findings (P<0.05). CONCLUSION: Serum S100B is normal in patients with focal epilepsy related or not to chronic NCC.
Assuntos
Epilepsia/sangue , Fatores de Crescimento Neural/sangue , Neurocisticercose/sangue , Proteínas S100/sangue , Doença Aguda , Adulto , Estudos de Casos e Controles , Eletroencefalografia , Epilepsia/diagnóstico , Feminino , Humanos , Masculino , Neurocisticercose/diagnóstico , Subunidade beta da Proteína Ligante de Cálcio S100RESUMO
Neuropsychological tests were applied to 20 patients with focal epilepsy related to calcified neurocysticercosis (NCC) (mean: three lesions/patient; NCC group), 22 patients with focal epilepsy without NCC (EPI group), and 29 healthy controls matched for age, sex, and educational level. The EPI and NCC groups were matched for age at onset of epilepsy, epilepsy duration, frequency of attacks, seizure semiology, interictal EEG findings, and antiepileptic drugs used. There were no differences in the digit span, word span, calculus, and Mini-Mental State examination among the three groups studied. The NCC and EPI groups showed lower scores than controls in immediate and delayed verbal memory, famous faces test, spatial recognition span, abstractions and judgment, and visuoconstructional abilities. The EPI group, but not the NCC group, also had lower scores in a praxis tests. There were no differences between the NCC and EPI groups in any of the tests applied (P > 15), except for the spatial recognition span, which was lower in the former. Cognitive impairment is a prevalent neuropsychological feature of patients with epilepsy and NCC.
RESUMO
We evaluated the effects of infusions of the NMDA receptor antagonist D,L-2-amino-5-phosphonopentanoic acid (AP5) into the basolateral nucleus of the amygdala (BLA) on the formation and expression of memory for inhibitory avoidance. Adult male Wistar rats (215-300 g) were implanted under thionembutal anesthesia (30 mg/kg, ip) with 9.0-mm guide cannulae aimed 1.0 mm above the BLA. Bilateral infusions of AP5 (5.0 microg) were given 10 min prior to training, immediately after training, or 10 min prior to testing in a step-down inhibitory avoidance task (0.3 mA footshock, 24-h interval between training and the retention test session). Both pre- and post-training infusions of AP5 blocked retention test performance. When given prior to the test, AP5 did not affect retention. AP5 did not affect training performance, and a control experiment showed that the impairing effects were not due to alterations in footshock sensitivity. The results suggest that NMDA receptor activation in the BLA is involved in the formation, but not the expression, of memory for inhibitory avoidance in rats. However, the results do not necessarily imply that the role of NMDA receptors in the BLA is to mediate long-term storage of fear-motivated memory within the amygdala.
Assuntos
2-Amino-5-fosfonovalerato/farmacologia , Tonsila do Cerebelo/efeitos dos fármacos , Aprendizagem da Esquiva/efeitos dos fármacos , Antagonistas de Aminoácidos Excitatórios/farmacologia , Receptores de N-Metil-D-Aspartato/efeitos dos fármacos , Tonsila do Cerebelo/química , Animais , Comportamento Animal , Teste de Esforço , Medo/efeitos dos fármacos , Imobilização , Masculino , Memória/efeitos dos fármacos , Condicionamento Físico Animal , Ratos , Ratos WistarRESUMO
We evaluated the effects of infusions of the NMDA receptor antagonist D,L-2-amino-5-phosphonopentanoic acid (AP5) into the basolateral nucleus of the amygdala (BLA) on the formation and expression of memory for inhibitory avoidance. Adult male Wistar rats (215-300 g) were implanted under thionembutal anesthesia (30 mg/kg, ip) with 9.0-mm guide cannulae aimed 1.0 mm above the BLA. Bilateral infusions of AP5 (5.0 µg) were given 10 min prior to training, immediately after training, or 10 min prior to testing in a step-down inhibitory avoidance task (0.3 mA footshock, 24-h interval between training and the retention test session). Both pre- and post-training infusions of AP5 blocked retention test performance. When given prior to the test, AP5 did not affect retention. AP5 did not affect training performance, and a control experiment showed that the impairing effects were not due to alterations in footshock sensitivity. The results suggest that NMDA receptor activation in the BLA is involved in the formation, but not the expression, of memory for inhibitory avoidance in rats. However, the results do not necessarily imply that the role of NMDA receptors in the BLA is to mediate long-term storage of fear-motivated memory within the amygdala.
Assuntos
Animais , Masculino , Ratos , 2-Amino-5-fosfonovalerato/farmacologia , Tonsila do Cerebelo/efeitos dos fármacos , Aprendizagem da Esquiva/efeitos dos fármacos , Antagonistas de Aminoácidos Excitatórios/farmacologia , Medo/efeitos dos fármacos , Receptores de N-Metil-D-Aspartato/efeitos dos fármacos , Comportamento Animal , Teste de Esforço , Imobilização , Memória/efeitos dos fármacos , Condicionamento Físico Animal , Ratos WistarRESUMO
6-Chloro-3'-nitroflavone integrates a list of nearly 70 flavone derivatives synthesized in our laboratories. The effects of 6-chloro-3'-nitroflavone on the benzodiazepine binding sites (BDZ-BSs) of the GABA(A) receptor were examined in vitro and in vivo. 6-Chloro-3'-nitroflavone inhibited the [3H]flunitrazepam ([3H]FNZ) binding to rat cerebral cortex membranes with a Ki of 6.68 nM and the addition of GABA to extensively washed membranes did not modify its affinity for the BDZ-BSs (GABA-shift = 1.16+/-0.12). The binding assays performed in rat striatal and cerebellar brain membranes showed that this compound has similar affinity to different populations of BDZ-BSs. Electrophysiological experiments revealed that 6-chloro-3'-nitroflavone did not affect GABA(A)-receptors (GABA(A)-Rs) responses recorded in Xenopus oocytes expressing alpha1beta2gamma2s subunits, but blocked the potentiation exerted by diazepam (DZ) on GABA-activated chloride currents. In vivo experiments showed that 6-chloro-3'-nitroflavone did not possess anxiolytic, anticonvulsant, sedative, myorelaxant actions in mice or amnestic effects in rats; however, 6-chloro-3'-nitroflavone antagonized diazepam-induced antianxiety action, anticonvulsion, short-term, and long-term amnesia and motor incoordination. These biochemical, electrophysiological, and pharmacological results suggest that 6-chloro-3'-nitroflavone behaves as an antagonist of the BDZ-BSs.
Assuntos
Diazepam/farmacologia , Flavonoides/farmacologia , Flunitrazepam/metabolismo , Moduladores GABAérgicos/farmacologia , Aprendizagem/efeitos dos fármacos , Atividade Motora/efeitos dos fármacos , Receptores de GABA-A/efeitos dos fármacos , Animais , Anticonvulsivantes , Diazepam/uso terapêutico , Antagonistas de Receptores de GABA-A , Masculino , Camundongos , Ratos , Ratos Wistar , Convulsões/tratamento farmacológico , XenopusRESUMO
Rats with cannulae implanted in the junction between the central and the basolateral nuclei of the amygdala were trained in one-trial step-down inhibitory avoidance and tested at 3 s for working memory (WM) or 1.5 or 24 h later for short-term memory (STM) and long-term memory (LTM), respectively. Several drugs were infused 6 min prior to training in the animals in which WM was measured or 0 min posttraining in those in which STM and LTM were measured: the glutamate receptor antagonists CNQX (0.5 microg) and AP5 (5.0 microg), the indirect GABA A receptor antagonist picrotoxin (0.08 microg), the cholinergic muscarinic receptor blocker scopolamine (2. 0 microg), norepinephrine (0.3 microg), the protein kinase C inhibitor staurosporin (1.0 microg), or the calcium/calmodulin dependent protein kinase II inhibitor Kn-62 (3.5 ng). None of the drugs had any effect on either WM or STM. All had, as previously shown, strong effects on LTM: picrotoxin and norepinephrine enhanced it, and CNQX, AP5, scopolamine, Kn-62, and staurosporin inhibited it. The results do not support the idea that memory of this task is formed in the amygdala; they indicate that the amygdala is not involved in WM or STM processing and support the idea that the amygdala modulates LTM storage processes carried out elsewhere.
Assuntos
Tonsila do Cerebelo/fisiologia , Memória de Curto Prazo/fisiologia , 1-(5-Isoquinolinasulfonil)-2-Metilpiperazina/análogos & derivados , 1-(5-Isoquinolinasulfonil)-2-Metilpiperazina/farmacologia , 6-Ciano-7-nitroquinoxalina-2,3-diona/farmacologia , Tonsila do Cerebelo/efeitos dos fármacos , Animais , Aprendizagem da Esquiva/efeitos dos fármacos , Aprendizagem da Esquiva/fisiologia , Inibidores Enzimáticos/farmacologia , Antagonistas de Aminoácidos Excitatórios/farmacologia , Antagonistas GABAérgicos/farmacologia , Masculino , Memória de Curto Prazo/efeitos dos fármacos , Antagonistas Muscarínicos/farmacologia , Norepinefrina/farmacologia , Picrotoxina/farmacologia , Ratos , Ratos Wistar , Escopolamina/farmacologia , Fatores de TempoRESUMO
Rats implanted bilaterally with cannulae in the CA1 region of the dorsal hippocampus or in the amygdala were trained in one-trial step-down inhibitory (passive) avoidance using a 0.4 mA footshock. At various times after training (0, 1.5, 3, 6 or 9 h for animals implanted in the hippocampus; 0 or 3 h for those implanted in the amygdala), they received infusions of 8-Br-cAMP (cyclic adenosine monophosphate) (1.25 micrograms/side), SKF38393 (7.5 micrograms/side), SCH23390 (0.5 microgram/side), norepinephrine ClH (0.3 microgram/side), timolol ClH (0.3 microgram/side), 8-HO-DPAT (2.5 micrograms/side), NAN-190 (2.5 micrograms/side), forskolin (0.5 microgram/side) or KT5720 (0.5 microgram/side). Rats were tested for retention 24 h after training. SKF38393 is an agonist and SCH23390 an antagonist at dopamine D1 receptors, timolol is a beta-adrenoceptor antagonist, 8-HO-DPAT is an agonist and NAN-190 an antagonist at 5HT1A receptors, forskolin enhances adenylyl cyclase, and KT5720 inhibits protein kinase A. When given into the hippocampus 0 h post-training, norepinephrine enhanced memory and KT5720 was amnestic. When given 1.5 h after training, all treatments were ineffective. When given 3 or 6 h post-training, 8-Br-cAMP, forskolin, SKF 38393, noradrenaline and NAN-190 caused memory facilitation, and KT5720, SCH23390, timolol and 8-HO-DPAT caused retrograde amnesia. At 9 h from training, all treatments were again ineffective. When given into the amygdala 0 or 3 h post-training all treatments were ineffective, except for noradrenaline at 0 h, which caused retrograde facilitation. The data agree with the suggestion that in the hippocampus, but not the amygdala, a cAMP/protein kinase A pathway is involved in memory consolidation at 3 and 6 h from training, and that this is regulated by D1, beta, and 5HT1A receptors. This correlates with a previous report of increased cAMP levels, protein kinase A activity and P-CREB levels at 3-6 h from training in rat hippocampus in this task. This may be taken to suggest that the hippocampus, but not the amygdala, is involved in the long-term storage of step-down inhibitory avoidance in the rat.
Assuntos
Carbazóis , Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , AMP Cíclico/metabolismo , Memória/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , 2,3,4,5-Tetra-Hidro-7,8-Di-Hidroxi-1-Fenil-1H-3-Benzazepina/farmacologia , 8-Hidroxi-2-(di-n-propilamino)tetralina/farmacologia , Agonistas alfa-Adrenérgicos/farmacologia , Antagonistas Adrenérgicos beta/farmacologia , Tonsila do Cerebelo , Animais , Aprendizagem da Esquiva , Benzazepinas/farmacologia , Colforsina/farmacologia , Proteínas Quinases Dependentes de AMP Cíclico/efeitos dos fármacos , Agonistas de Dopamina/farmacologia , Antagonistas de Dopamina/farmacologia , Hipocampo , Indóis/farmacologia , Masculino , Norepinefrina/farmacologia , Piperazinas/farmacologia , Pirróis/farmacologia , Ratos , Ratos Wistar , Receptores Adrenérgicos beta/efeitos dos fármacos , Receptores de Dopamina D1/efeitos dos fármacos , Receptores de Serotonina/efeitos dos fármacos , Antagonistas da Serotonina/farmacologia , Agonistas do Receptor de Serotonina/farmacologia , Fatores de Tempo , Timolol/farmacologiaRESUMO
Male Wistar rats were trained in one-trial step-down inhibitory avoidance using a 0.4-mA footshock. At various times after training (0, 1.5, 3, 6 and 9 h for the animals implanted into the CA1 region of the hippocampus; 0 and 3 h for those implanted into the amygdala), these animals received microinfusions of SKF38393 (7.5 micrograms/side), SCH23390 (0.5 microgram/side), norepinephrine (0.3 microgram/side), timolol (0.3 microgram/side), 8-OH-DPAT (2.5 micrograms/side), NAN-190 (2.5 micrograms/side), forskolin (0.5 microgram/side), KT5720 (0.5 microgram/side) or 8-Br-cAMP (1.25 micrograms/side). Rats were tested for retention 24 h after training. When given into the hippocampus 0 h post-training, norepinephrine enhanced memory whereas KT5720 was amnestic. When given 1.5 h after training, all treatments were ineffective. When given 3 or 6 h post-training, 8-Br-cAMP, forskolin, SKF38393, norepinephrine and NAN-190 caused memory facilitation, while KT5720, SCH23390, timolol and 8-OH-DPAT caused retrograde amnesia. Again, at 9 h after training, all treatments were ineffective. When given into the amygdala, norepinephrine caused retrograde facilitation at 0 h after training. The other drugs infused into the amygdala did not cause any significant effect. These data suggest that in the hippocampus, but not in the amygdala, a cAMP/protein kinase A pathway is involved in memory consolidation at 3 and 6 h after training, which is regulated by D1, beta, and 5HT1A receptors. This correlates with data on increased post-training cAMP levels and a dual peak of protein kinase A activity and CREB-P levels (at 0 and 3-6 h) in rat hippocampus after training in this task. These results suggest that the hippocampus, but not the amygdala, is involved in long-term storage of step-down inhibitory avoidance in the rat.
Assuntos
Tonsila do Cerebelo/efeitos dos fármacos , Proteínas Quinases Dependentes de AMP Cíclico/efeitos dos fármacos , AMP Cíclico/análise , Hipocampo/efeitos dos fármacos , Memória/fisiologia , 8-Bromo Monofosfato de Adenosina Cíclica/farmacologia , 8-Hidroxi-2-(di-n-propilamino)tetralina/farmacologia , Animais , Benzazepinas/farmacologia , Colforsina/farmacologia , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/análise , Masculino , Norepinefrina/farmacologia , Ratos , Ratos Wistar , Transdução de SinaisRESUMO
Male Wistar rats were trained in one-trial step-down inhibitory avoidance using a 0.4-mA footshock. At various times after training (0, 1.5, 3,6 and 9 h for the animals implanted into the CA1 region of the hippocampus; 0 and 3 h for those implanted into the amygdala), these animals received microinfusions of SKF38393 (7.5 mug/side), SCH23390 (0.5 mug/side), norepinephrine (0.3 mug/side), timolol (0.3 mug/side), 8-OH-DPAT (2.5 mug/side), NAN-190 (2.5 mug/side), forskolin (0.5 mug/side), KT5720 (0.5 mug/side) or 8-Br-cAMP (1.25 mug/side). Rats were tested for retention 24 h after training. When given into the hippocampus 0 h post-training, norepinephrine enhanced memory whereas KT5720 was amnestic. When given 1.5 h after training, all treatments were ineffective. When given 3 or 6 h post-training, 8-Br-cAMP, forskolin, SKF38393, norepinephrine and NAN-190 caused memory facilitation, while KT5720, SCH23390, timolol and 8-OH-DPAT caused retrograde amnesia. Again, at 9 h after training, all treatments were inffective. When given into the amygdala, norepinephrine caused retrograde facilitation at 0 h after training. The other drugs infused into the amygdala did not cause any significant effect. These data suggest that in the hippocampus, but not in the amygdala, a cAMP/protein kinase A pathway is involved in memory cosolidation at 3 and 6 h after training, which is regulated by D1, Beta, and 5HT1A receptors. This correlates with data on increased post-training cAMP levels and a dual peak of protein kinase A activity and CREB-P levels (at 0 and 3-6 h) in rat hippocampus after training in this task. These results suggest that the hippocampus, but not the amygdala, is involved in long-term storage of step-down inhibitory avoidance in the rat.
Assuntos
Ratos , Animais , Masculino , Tonsila do Cerebelo/efeitos dos fármacos , Proteínas Quinases Dependentes de AMP Cíclico/efeitos dos fármacos , AMP Cíclico/análise , Hipocampo/efeitos dos fármacos , Memória/fisiologia , 8-Bromo Monofosfato de Adenosina Cíclica/farmacologia , 8-Hidroxi-2-(di-n-propilamino)tetralina/farmacologia , Benzazepinas/farmacologia , Colforsina/farmacologia , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/análise , Norepinefrina/farmacologia , Ratos Wistar , Transdução de SinaisRESUMO
cAMP/cAMP-dependent protein kinase (PKA) signaling pathway has been recently proposed to participate in both the late phase of long term potentiation in the hippocampus and in the late, protein synthesis-dependent phase of memory formation. Here we report that a late memory consolidation phase of an inhibitory avoidance learning is regulated by an hippocampal cAMP signaling pathway that is activated, at least in part, by D1/D5 receptors. Bilateral infusion of SKF 38393 (7.5 microg/side), a D1/D5 receptor agonist, into the CA1 region of the dorsal hippocampus, enhanced retention of a step-down inhibitory avoidance when given 3 or 6 h, but not immediately (0 h) or 9 h, after training. In contrast, full retrograde amnesia was obtained when SCH 23390 (0.5 microg/side), a D1/D5 receptor antagonist, was infused into the hippocampus 3 or 6 h after training. Intrahippocampal infusion of 8Br-cAMP (1.25 microg/side), or forskolin (0.5 microg/side), an activator of adenylyl cyclase, enhanced memory when given 3 or 6 h after training. KT5720 (0.5 microg/side), a specific inhibitor of PKA, hindered memory consolidation when given immediately or 3 or 6 h posttraining. Rats submitted to the avoidance task showed learning-specific increases in hippocampal 3H-SCH 23390 binding and in the endogenous levels of cAMP 3 and 6 h after training. In addition, PKA activity and P-CREB (phosphorylated form of cAMP responsive element binding protein) immunoreactivity increased in the hippocampus immediately and 3 and 6 h after training. Together, these findings suggest that the late phase of memory consolidation of an inhibitory avoidance is modulated cAMP/PKA signaling pathways in the hippocampus.