RESUMEN
The relationship between serotonin dysfunction and schizophrenia commenced with the discovery of the effects of lysergic acid diethylamide (LSD) that has high affinity for 5-HT2A receptors. Activation of these receptors produces perceptual and behavioural changes such as illusions, visual hallucinations and locomotor hyperactivity. Using prepulse inhibition (PPI) of the acoustic startle, which is impaired in schizophrenia,we aimed to investigate:i) the existence of a direct and potentially inhibitory neural pathway between the inferior colliculus (IC) and the pedunculopontine tegmental nucleus (PPTg) involved in the mediation of PPI responses by a neural tract tracing procedure;ii) if the microinjection of the 5-HT2A receptors agonist DOI in IC would activate neurons in this structure and in the PPTg by a c-Fos protein immunohistochemistry study;iii) whether the deficits in PPI responses, observed after the administration of DOI in the IC, could be prevented by the concomitant microinjection of the GABAA receptor antagonist bicuculline in the PPTg.Male Wistar rats were used in this study. An IC-PPTg reciprocated neuronal pathway was identified by neurotracing. The number of c-Fos labelled cells was lower in the DOI group in IC and PPTg, suggesting that this decrease could be due to the high levels of GABA in both structures. The concomitant microinjections of bicuculline in PPTg and DOI in IC prevented the PPI deficit observed after the IC microinjection of DOI. Our findings suggest that IC 5-HT2A receptors may be at least partially involved in the regulation of inhibitory pathways mediating PPI response in IC and PPTg structures.
Asunto(s)
Colículos Inferiores , Núcleo Tegmental Pedunculopontino , Ratas , Animales , Masculino , Inhibición Prepulso/fisiología , Reflejo de Sobresalto/fisiología , Receptores de GABA-A , Receptor de Serotonina 5-HT2A , Bicuculina/farmacología , Serotonina/farmacología , Ratas WistarRESUMEN
Resumen La patología del sistema nervioso central, habitualmente, no provoca síntomas auditivos unilaterales, ya que la vía auditiva central está formada por una red de conexiones cruzadas entre los diferentes núcleos que la forman. Además, hay que considerar que una lesión pequeña puede extenderse a más de una estructura provocando varios déficits neurológicos debido a la proximidad de los tractos y núcleos nerviosos. Las lesiones unilaterales circunscritas en el colículo inferior son infrecuentes. No obstante, se han descrito casos en los que lesiones unilaterales de diversas etiologías en esta localización causaban síntomas auditivos. Ya que la vía auditiva central es cruzada, síntomas auditivos detectados con más frecuencia afectaban concretamente a la capacidad de localización del sonido o la comprensión verbal. Presentamos el caso de un hombre de 44 años con acúfeno unilateral derecho de larga evolución, sin otra clínica asociada quien fue diagnosticado de un tumor en el colículo inferior derecho mediante resonancia magnética cerebral. Se exponen los hallazgos clínicos y radiológicos del caso.
Abstract Central nervous system diseases usually do not cause auditory symptoms because the central auditory pathway consists on a network of crossed connections between the different nuclei that form it. In addition, we must consider that a small lesion might extend to more than one structure producing many neurologic symptoms due to the proximity of tracts and nuclei in the midbrain. Unilateral circumscribed lesions at inferior colliculus are rare. Nevertheless, lesions at this location causing auditory symptoms have been described. Because of the crossed central auditory pathway, the most commonly detected auditory symptoms specifically affected the ability to locate sound or verbal comprehension. We present the case of a 44-year-old man with a long-term monoaural right-sided tinnitus without other complaints who was diagnosed of a tumour at right inferior colliculus by neuroimaging. Clinical and radiological findings of this case are discussed.
Asunto(s)
Humanos , Masculino , Adulto , Acúfeno/complicaciones , Colículos Inferiores/patología , Espectroscopía de Resonancia Magnética , Enfermedades del Sistema Nervioso Central , NeoplasiasRESUMEN
Three new species of Microlaimus are described from the continental shelf of the Campos Basin, southwest Atlantic, Brazil. Microlaimus campiensis sp. n. differs from all other species in the presence of two anterior testes, slender spicules with enlarged proximal ends, 7-11 pre-cloacal papilliform supplements, and females with a pair of constriction structures, one on each branch of the ovary. Microlaimus alexandri sp. n. shows sexual dimorphism in the size of the amphidial fovea, which occupies 100% of the diameter of the corresponding area in the male; the buccal cavity provided with five teeth and a slightly cuticularized cuticular ring. Microlaimus vitorius sp. n. has four longitudinal-lateral rows of glands associated with small pores, one seta and three pores small pre-cloacal, and the gubernaculum has a triangular base. An amendment to the diagnosis of the genus is proposed, where the number of teeth was modified.
Asunto(s)
Colículos Inferiores , Nematodos , Animales , Femenino , Masculino , Chromadorea , Brasil , Suplementos DietéticosRESUMEN
Hypomyelination with atrophy of the basal ganglia and cerebellum (H-ABC) is a neurodegenerative disease due to mutations in TUBB4A. Patients suffer from extrapyramidal movements, spasticity, ataxia, and cognitive deficits. Magnetic resonance imaging features are hypomyelination and atrophy of the striatum and cerebellum. A correlation between the mutations and their cellular, tissue and organic effects is largely missing. The effects of these mutations on sensory functions have not been described so far. We have previously reported a rat carrying a TUBB4A (A302T) mutation and sharing most of the clinical and radiological signs with H-ABC patients. Here, for the first time, we did a comparative study of the hearing function in an H-ABC patient and in this mutant model. By analyzing hearing function, we found that there are no significant differences in the auditory brainstem response (ABR) thresholds between mutant rats and WT controls. Nevertheless, ABRs show longer latencies in central waves (II-IV) that in some cases disappear when compared to WT. The patient also shows abnormal AEPs presenting only Waves I and II. Distortion product of otoacoustic emissions and immunohistochemistry in the rat show that the peripheral hearing function and morphology of the organ of Corti are normal. We conclude that the tubulin mutation severely impairs the central hearing pathway most probably by progressive central white matter degeneration. Hearing function might be affected in a significant fraction of patients with H-ABC; therefore, screening for auditory function should be done on patients with tubulinopathies to evaluate hearing support therapies.
Asunto(s)
Discapacidades del Desarrollo/genética , Trastornos Distónicos/genética , Pérdida Auditiva Sensorineural/genética , Tubulina (Proteína)/deficiencia , Sustitución de Aminoácidos , Animales , Percepción Auditiva , Preescolar , Núcleo Coclear/patología , Enfermedades Desmielinizantes/genética , Modelos Animales de Enfermedad , Oído Interno/fisiopatología , Potenciales Evocados Auditivos , Femenino , Pérdida Auditiva Sensorineural/fisiopatología , Humanos , Colículos Inferiores/patología , Masculino , Mutación Missense , Vaina de Mielina/patología , Mutación Puntual , Ratas , Ratas Mutantes , Ratas Sprague-Dawley , Tubulina (Proteína)/genéticaRESUMEN
It has been shown that fear conditioning improves the steady-state evoked potentials driven by a long lasting amplitude modulated tone in the inferior colliculus. In this work we tested the hypothesis that the amygdala modulates this effect, since it plays a crucial role in assessing the biological relevance of environmental stimuli. We inhibited the basolateral nucleus of the amygdala of rats by injecting a GABAa receptor agonist (muscimol) before the recall test session of an auditory fear conditioning paradigm and recorded the evoked activity in the central nucleus of the inferior colliculus. According to our results, the treatment with muscimol decreased the expression of freezing behavior during the recall test session, but did not impair the entrainment of the evoked activity in the inferior colliculus induced by fear conditioning. We repeated the injection protocol with another group of rats but without pairing the tone to an aversive stimulus and observed that the inhibition of the basolateral amygdala enhances the stimulus-driven activity in the inferior colliculus regardless of the conditioning task. Our findings suggest that the basolateral amygdala exerts a tonic modulation over the encoding of sensory information at the early stages of the sensory pathway.
Asunto(s)
Amígdala del Cerebelo/fisiología , Condicionamiento Clásico/fisiología , Potenciales Evocados/fisiología , Miedo/fisiología , Colículos Inferiores/fisiología , Estimulación Acústica , Amígdala del Cerebelo/efectos de los fármacos , Animales , Conducta Animal/efectos de los fármacos , Conducta Animal/fisiología , Condicionamiento Clásico/efectos de los fármacos , Potenciales Evocados/efectos de los fármacos , Agonistas de Receptores de GABA-A/farmacología , Colículos Inferiores/efectos de los fármacos , Masculino , Muscimol/farmacología , Ratas , Ratas WistarRESUMEN
BACKGROUND: Gamma-aminobutyric acid (GABA)ergic and opioid systems play a crucial role in the neural modulation of innate fear organised by the inferior colliculus (IC). In addition, the IC is rich in GABAergic fibres and opioid neurons, which are also connected to other mesencephalic structures, such as the superior colliculus and the substantia nigra. However, the contribution of distinct opioid receptors (ORs) in the IC during the elaboration and expression of innate fear and panic-like responses is unclear. The purpose of the present work was to investigate a possible integrated action exerted by ORs and the GABAA receptor-mediated system in the IC on panic-like responses. METHODS: The effect of the blockade of either µ1- or κ-ORs in the IC was evaluated in the unconditioned fear-induced responses elicited by GABAA antagonism with bicuculline. Microinjections of naloxonazine, a µ1-OR antagonist, or nor-binaltorphimine (nor-BNI), a κ-OR antagonist, were made into the IC, followed by intramesencephalic administration of the GABAA-receptor antagonist bicuculline. The defensive behaviours elicited by the treatments in the IC were quantitatively analysed, recording the number of escapes expressed as running (crossing), jumps, and rotations, over a 30-min period in a circular arena. The exploratory behaviour of rearing was also recorded. RESULTS: GABAA-receptor blockade with bicuculline in the IC increased defensive behaviours. However, pretreatment of the IC with higher doses (5 µg) of naloxonazine or nor-BNI followed by bicuculline resulted in a significant decrease in unconditioned fear-induced responses. CONCLUSIONS: These findings suggest a role played by µ1- and κ-OR-containing connexions and GABAA receptor-mediated neurotransmission on the organisation of panic attack-related responses elaborated by the IC neurons.
Asunto(s)
Conducta Animal/efectos de los fármacos , Colículos Inferiores/efectos de los fármacos , Mesencéfalo/efectos de los fármacos , Antagonistas de Narcóticos/farmacología , Pánico/efectos de los fármacos , Receptores Opioides kappa/antagonistas & inhibidores , Receptores Opioides mu/antagonistas & inhibidores , Animales , Bicuculina/farmacología , Conducta Exploratoria/efectos de los fármacos , Antagonistas de Receptores de GABA-A/farmacología , Masculino , Naloxona/análogos & derivados , Naloxona/farmacología , Naltrexona/análogos & derivados , Naltrexona/farmacología , Neuronas/efectos de los fármacos , Ratas , Ratas WistarRESUMEN
BACKGROUND: The endogenous opioid peptide system has been implicated in the neural modulation of fear and anxiety organised by the dorsal midbrain. Furthermore, previous results indicate a fundamental role played by inferior colliculus (IC) opioid mechanisms during the expression of defensive behaviours, but the involvement of the IC µ1-opioid receptor in the modulation of anxiety- and panic attack-related behaviours remains unclear. Using a prey-versus-snake confrontation paradigm, we sought to investigate the effects of µ1-opioid receptor blockade in the IC on the defensive behaviour displayed by rats in a dangerous situation. METHODS: Specific pathogen-free Wistar rats were treated with microinjection of the selective µ1-opioid receptor antagonist naloxonazine into the IC at different concentrations (1.0, 3.0 and 5.0 µg/0.2 µL) and then confronted with rattlesnakes ( Crotalus durissus terrificus). The defensive behavioural repertoire, such as defensive attention, flat back approach (FBA), startle, defensive immobility, escape or active avoidance, displayed by rats either during the confrontations with wild snakes or during re-exposure to the experimental context without the predator was analysed. RESULTS: The blockade of µ1-opioid receptors in the IC decreased the expression of both anxiety-related behaviours (defensive attention, FBA) and panic attack-related responses (startle, defensive immobility and escape) during the confrontation with rattlesnakes. A significant decrease in defensive attention was also recorded during re-exposure of the prey to the experimental apparatus context without the predator. CONCLUSION: Taken together, these results suggest that a decrease in µ1-opioid receptor signalling activity within the IC modulates anxiety- and panic attack-related behaviours in dangerous environments.
Asunto(s)
Ansiedad/prevención & control , Conducta Animal/efectos de los fármacos , Miedo , Colículos Inferiores/efectos de los fármacos , Antagonistas de Narcóticos/farmacología , Trastorno de Pánico/prevención & control , Receptores Opioides mu/antagonistas & inhibidores , Transducción de Señal/efectos de los fármacos , Animales , Crotalus , Modelos Animales de Enfermedad , Cadena Alimentaria , Naloxona/análogos & derivados , Naloxona/farmacología , Ratas , Ratas WistarRESUMEN
It has been established that chemical stimulation of the inferior colliculus (IC) of laboratory animals evokes fear-related defensive responses, which are considered panic attack-like behaviours. In addition, there is evidence that defensive reactions provoked by chemical stimulation of midbrain tectum neurons may induce an antinociceptive response. Morphologically, the IC receives projections from other mesencephalic structures, such as the dorsal raphe nucleus (DRN), a region rich in serotonergic neurons that play a critical role in the control of defensive behaviours. Moreover, this monoaminergic brainstem reticular nucleus is suggested to comprise the endogenous pain modulatory system. The aim of the present study was to investigate the role of DRN 5-hydroxytryptamine 2A (5-HT2A) receptors in Wistar rats by local microinjection of R-96544 (a selective antagonist of the 5-HT2A receptor) at doses of 5, 10 or 15â¯nM on defensive reactions and fear-induced antinociception evoked by chemical stimulation of the central nucleus of the IC with NMDA (6, 9 or 12 nmol). Behavioural responses were analysed for 10â¯min, and then the nociceptive threshold was measured at 10â¯min intervals for 70â¯min. The dose of 12â¯nmol of NMDA was the most effective in causing panic attack-like defensive behaviours and much higher hypoalgesia. In addition, both effects were attenuated by pretreatment of the DRN with R-96544. These findings suggest the critical participation of DRN 5-HT2A receptors in the modulation of panic attack-like defensive behaviour and unconditioned fear-induced antinociception organised by neurons in the central nucleus of the IC.
Asunto(s)
Miedo/psicología , Colículos Inferiores/citología , Neuronas/fisiología , Nocicepción/fisiología , Dolor/psicología , Receptor de Serotonina 5-HT2A/metabolismo , Animales , Condicionamiento Psicológico/fisiología , Modelos Animales de Enfermedad , Núcleo Dorsal del Rafe , Relación Dosis-Respuesta a Droga , Agonistas de Aminoácidos Excitadores/farmacología , Reacción Cataléptica de Congelación/efectos de los fármacos , Masculino , N-Metilaspartato/farmacología , Neuronas/efectos de los fármacos , Nocicepción/efectos de los fármacos , Dolor/tratamiento farmacológico , Umbral del Dolor/efectos de los fármacos , Umbral del Dolor/fisiología , Pirrolidinas/farmacología , Ratas , Ratas Wistar , Estadísticas no ParamétricasRESUMEN
BACKGROUND: There is a controversy regarding the key role played by opioid peptide neurotransmission in the modulation of panic-attack-related responses. AIMS: Using a prey versus rattlesnakes paradigm, the present work investigated the involvement of the endogenous opioid peptide-mediated system of the inferior colliculus in the modulation of panic attack-related responses. METHODS: Wistar rats were pretreated with intracollicular administration of either physiological saline or naloxone at different concentrations and confronted with rattlesnakes ( Crotalus durissus terrificus). The prey versus rattlesnake confrontations were performed in a polygonal arena for snakes. The defensive behaviors displayed by prey (defensive attention, defensive immobility, escape response, flat back approach and startle) were recorded twice: firstly, over a period of 15 min the presence of the predator and a re-exposure was performed 24 h after the confrontation, when animals were exposed to the experimental enclosure without the rattlesnake. RESULTS: The intramesencephalic non-specific blockade of opioid receptors with microinjections of naloxone at higher doses decreased both anxiety- (defensive attention and flat back approach) and panic attack-like (defensive immobility and escape) behaviors, evoked in the presence of rattlesnakes and increased non-defensive responses. During the exposure to the experimental context, there was a decrease in duration of defensive attention. CONCLUSIONS: These findings suggest a panicolytic-like effect of endogenous opioid receptors antagonism in the inferior colliculus on innate (panic attack) and conditioned (anticipatory anxiety) fear in rats threatened by rattlesnakes.
Asunto(s)
Miedo/efectos de los fármacos , Colículos Inferiores/efectos de los fármacos , Naloxona/farmacología , Péptidos Opioides/fisiología , Trastorno de Pánico/tratamiento farmacológico , Animales , Reacción de Prevención/efectos de los fármacos , Crotalus , Mecanismos de Defensa , Reacción de Fuga/efectos de los fármacos , Miedo/psicología , Colículos Inferiores/fisiología , Masculino , Péptidos Opioides/antagonistas & inhibidores , Ratas , Ratas WistarRESUMEN
Auditory-evoked potentials (AEPs) can be modified by associative learning, where the appearance of learned compensatory responses (CCRs) may result in the emergence of drug withdrawal symptoms and relapse. Although CCRs' influence on later attentive and cognitive domains has been extensively examined, contextual conditioned tolerance occurring in preattentive mechanisms operating at earlier stages of information processing has remained largely unexplored. To extend our knowledge on this subject, compensatory changes on the motor and emotional aspects of behavior evoked by contextual cues were investigated with an electronic open field in morphine-pretreated rats challenged with two morphine overdoses (40 and 80â¯mg/kg). CCRs influence on the AEPs recorded in the central nucleus of the inferior colliculus (CIC) was analyzed with the help of a field potential recording device and a two-chamber shuttle box placed inside a Faraday cage system. The emergence of electrophysiological CCRs was analyzed by recording AEP latency and amplitude elicited in the central nucleus of the IC (CIC) with the aid of a field potential recording device and a two-chamber shuttle box placed inside a Faraday cage system. Behavioral analysis indicated that CCRs ensue in non-familiar contexts. Electrophysiological data revealed increases in the amplitude of AEPs evoked in a non-familiar context. Our results indicate that behavioral learning responses emerge following Pavlovian conditioning even with the use of low and regular doses of morphine over a short-term treatment. Changes in the CIC electrophysiology may indicate that the development of drug dependence occurs covertly in the early stages of sensory information processing.
Asunto(s)
Condicionamiento Clásico/efectos de los fármacos , Potenciales Evocados Auditivos/efectos de los fármacos , Colículos Inferiores/efectos de los fármacos , Colículos Inferiores/fisiología , Morfina/administración & dosificación , Refuerzo en Psicología , Animales , Conducta Animal/efectos de los fármacos , Señales (Psicología) , Masculino , Ratas WistarRESUMEN
BACKGROUND: Canine visceral leishmaniasis (CVL) is endemic in São Luís Maranhão/Brazil and it leads a varied clinical picture, including neurological signs. RESULTS: Histopathological evaluation showed that 14 dogs exhibited pathological alterations in at least one of the analyzed areas. Of these, mononuclear inflammatory reaction was the most frequent, although other lesions, such as hemorrhage, chromatolysis and gliosis were also observed. The presence of L. infantum amastigotes was confirmed in eight dogs, identified in four regions: telencephalon, hippocampus, thalamus and caudal colliculus, but only one presented neurological signs. Polymerase chain reaction results detected the DNA of the parasite in 11 samples from seven dogs. The positive areas were the telencephalon, thalamus, hippocampus, cerebellum, caudal and rostral colliculus. CONCLUSION: These results reveal that during canine visceral leishmaniasis, the central nervous system may display some alterations, without necessarily exhibiting clinical neurological manifestations. In addition, the L. infantum parasite has the ability to cross the blood brain barrier and penetrate the central nervous system.
Asunto(s)
Sistema Nervioso Central/parasitología , Enfermedades de los Perros/parasitología , Leishmania infantum , Leishmaniasis Visceral/veterinaria , Animales , Sistema Nervioso Central/patología , ADN Protozoario/genética , Enfermedades de los Perros/patología , Perros , Femenino , Hipocampo/parasitología , Hipocampo/patología , Colículos Inferiores/parasitología , Colículos Inferiores/patología , Leishmania infantum/genética , Leishmaniasis Visceral/parasitología , Leishmaniasis Visceral/patología , Masculino , Reacción en Cadena de la Polimerasa/veterinaria , Telencéfalo/parasitología , Telencéfalo/patología , Tálamo/parasitología , Tálamo/patologíaRESUMEN
The rat inferior colliculus (IC) is a major midbrain relay for ascending inputs from the auditory brain stem and has been suggested to play a key role in the processing of aversive sounds. Previous studies have demonstrated that auditory fear conditioning (AFC) potentiates transient responses to brief tones in the IC, but it remains unexplored whether AFC modifies responses to sustained periodic acoustic stimulation-a type of response called the steady-state evoked potential (SSEP). Here we used an amplitude-modulated tone-a 10-kHz tone with a sinusoidal amplitude modulation of 53.7 Hz-as the conditioning stimulus (CS) in an AFC protocol (5 CSs per day in 3 consecutive days) while recording local field potentials (LFPs) from the IC. In the preconditioning session (day 1), the CS elicited prominent 53.7-Hz SSEPs. In the training session (day 2), foot shocks occurred at the end of each CS (paired group) or randomized in the inter-CS interval (unpaired group). In the test session (day 3), SSEPs markedly differed from preconditioning in the paired group: in the first two trials the phase to which the SSEP coupled to the CS amplitude envelope shifted ~90°; in the last two trials the SSEP power and the coherence of SSEP with the CS amplitude envelope increased. LFP power decreased in frequency bands other than 53.7 Hz. In the unpaired group, SSEPs did not change in the test compared with preconditioning. Our results show that AFC causes dissociated changes in the phase and power of SSEP in the IC.NEW & NOTEWORTHY Local field potential oscillations in the inferior colliculus follow the amplitude envelope of an amplitude-modulated tone, originating a neural response called the steady-state evoked potential. We show that auditory fear conditioning of an amplitude-modulated tone modifies two parameters of the steady-state evoked potentials in the inferior colliculus: first the phase to which the evoked oscillation couples to the amplitude-modulated tone shifts; subsequently, the evoked oscillation power increases along with its coherence with the amplitude-modulated tone.
Asunto(s)
Condicionamiento Clásico , Potenciales Evocados Auditivos , Miedo/fisiología , Colículos Inferiores/fisiología , Estimulación Acústica , Animales , Ondas Encefálicas , Masculino , Ratas WistarRESUMEN
Abstract Introduction: Salicylate at high doses induces tinnitus in humans and experimental animals. However, the mechanisms and loci of action of salicylate in inducing tinnitus are still not well known. The expression of Immediate Early Genes (IEG) is traditionally associated with long-term neuronal modifications but it is still not clear how and where IEGs are activated in animal models of tinnitus. Objectives: Here we investigated the expression of c-fos and Egr-1, two IEGs, in the Dorsal Cochlear Nucleus (DCN), the Inferior Colliculus (IC), and the Posterior Ventral Cochlear Nucleus (pVCN) of rats. Methods: Rats were treated with doses known to induce tinnitus in rats (300 mg/kg i.p. daily, for 3 days), and c-fos and Egr-1 protein expressions were analyzed using western blot and immunocytochemistry. Results: After administration of salicylate, c-fos protein expression increased significantly in the DCN, pVCN and IC when assayed by western blot. Immunohistochemistry staining showed a more intense labeling of c-fos in the DCN, pVCN and IC and a significant increase in c-fos positive nuclei in the pVCN and IC. We did not detect increased Egr-1 expression in any of these areas. Conclusion: Our data show that a high dose of salicylate activates neurons in the DCN, pVCN and IC. The expression of these genes by high doses of salicylate strongly suggests that plastic changes in these areas are involved in the genesis of tinnitus.
Resumo Introdução: Salicilato em doses elevadas induz zumbido nos seres humanos e em animais experimentais. No entanto, os mecanismos e loci de ação do salicilato na indução de zumbido ainda não são bem conhecidos. A expressão dos genes precoces imediatos (GPIs) está tradicionalmente associada a alterações neuronais em longo prazo, mas ainda não está claro como e onde os GPIs são ativados em modelos animais de zumbido. Objetivos: No presente estudo investigamos a expressão de c-fos e Egr-1, dois GPIs, no núcleo coclear dorsal (NCD), colículo inferior (CI) e núcleo coclear ventral posterior (NCVp) de ratos. Métodos: Os ratos foram tratados com doses que, conhecidamente, induzem zumbido em ratos (300 mg/kg IP/dia, por três dias) e as expressões das proteínas c-fos e Egr-1 foram analisadas por meio de Western blot e imunoistoquímica. Resultados: Após a administração de salicilato, a expressão da proteína c-fos aumentou significativamente no NCD, NCVp e CI, quando analisados por Western blot. A coloração imunoistoquímica mostrou uma marcação mais intensa de c-fos no NCD, NCVp e CI e um aumento significativo de núcleos positivos de c-fos no NCVp e CI. Não detectamos aumento da expressão de Egr-1 em qualquer dessas áreas. Conclusão: Nossos dados mostram que uma dose alta de salicilato ativa neurônios no NCD, NCVp e CI. A expressão desses genes por doses altas de salicilato sugere que as alterações plásticas nessas áreas estão envolvidas na gênese do zumbido.
Asunto(s)
Animales , Masculino , Ratas , Colículos Inferiores/efectos de los fármacos , Salicilatos/farmacología , Regulación de la Expresión Génica/efectos de los fármacos , Genes Inmediatos-Precoces/efectos de los fármacos , Núcleo Coclear/efectos de los fármacos , Salicilatos/administración & dosificación , Western Blotting , Genes fos/efectos de los fármacos , Ratas Wistar , Relación Dosis-Respuesta a Droga , Proteína 1 de la Respuesta de Crecimiento Precoz/efectos de los fármacosRESUMEN
Epilepsy is a neurological disease related to the occurrence of pathological oscillatory activity, but the basic physiological mechanisms of seizure remain to be understood. Our working hypothesis is that specific sensory processing circuits may present abnormally enhanced predisposition for coordinated firing in the dysfunctional brain. Such facilitated entrainment could share a similar mechanistic process as those expediting the propagation of epileptiform activity throughout the brain. To test this hypothesis, we employed the Wistar audiogenic rat (WAR) reflex animal model, which is characterized by having seizures triggered reliably by sound. Sound stimulation was modulated in amplitude to produce an auditory steady-state-evoked response (ASSR; -53.71Hz) that covers bottom-up and top-down processing in a time scale compatible with the dynamics of the epileptic condition. Data from inferior colliculus (IC) c-Fos immunohistochemistry and electrographic recordings were gathered for both the control Wistar group and WARs. Under 85-dB SLP auditory stimulation, compared to controls, the WARs presented higher number of Fos-positive cells (at IC and auditory temporal lobe) and a significant increase in ASSR-normalized energy. Similarly, the 110-dB SLP sound stimulation also statistically increased ASSR-normalized energy during ictal and post-ictal periods. However, at the transition from the physiological to pathological state (pre-ictal period), the WAR ASSR analysis demonstrated a decline in normalized energy and a significant increase in circular variance values compared to that of controls. These results indicate an enhanced coordinated firing state for WARs, except immediately before seizure onset (suggesting pre-ictal neuronal desynchronization with external sensory drive). These results suggest a competing myriad of interferences among different networks that after seizure onset converge to a massive oscillatory circuit.
Asunto(s)
Corteza Auditiva/fisiopatología , Potenciales Evocados Auditivos , Colículos Inferiores/fisiopatología , Convulsiones/fisiopatología , Estimulación Acústica , Animales , Corteza Auditiva/metabolismo , Sincronización Cortical , Modelos Animales de Enfermedad , Electroencefalografía , Colículos Inferiores/metabolismo , Vías Nerviosas/fisiopatología , Proteínas Proto-Oncogénicas c-fos/metabolismo , Ratas , Ratas WistarRESUMEN
Dysfunctions of the serotonergic system have been suggested to be important in the neurobiology of schizophrenia. Patients with schizophrenia exhibit deficits in an operational measure of sensorimotor gating: prepulse inhibition (PPI) of startle. PPI is the normal reduction in the startle response caused by a low intensity non-startling stimulus (prepulse) which is presented shortly before the startle stimulus (pulse). The hallucinogen 2,5-dimethoxy-4-iodoamphetamine (DOI), a 5-hydroxytryptamine(HT)2 receptor agonist disrupted PPI in rats. The inferior colliculus (IC) is a critical nucleus of the auditory pathway mediating acoustic PPI. The activation of the IC by the acoustic prepulse reduces startle magnitude. The present study investigated the role of serotonergic transmission in the IC on the expression of acoustic PPI. For that we investigated whether 5-HT2A receptor activation or blockade would affect this response. Unilateral microinjection of DOI (10µg/0.3µl) into the IC disrupted PPI, while microinjection of the 5-HT2A receptor antagonist ritanserin (4µg/0.3µl), into this structure did not alter PPI. We also examined the ability of the atypical antipsychotic clozapine (5.0mg/kg; I.P.) to reverse the disruption of PPI produced by unilateral microinjections of DOI into the IC of rats. Pretreatment with clozapine blocked DOI-induced disruption of PPI. Altogether, these results suggest that serotonin-mediated mechanisms of the IC are involved in the expression of PPI in rodents and that this response is sensitive to atypical antipsychotic clozapine.
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Anfetaminas/administración & dosificación , Antipsicóticos/administración & dosificación , Clozapina/administración & dosificación , Colículos Inferiores/efectos de los fármacos , Colículos Inferiores/fisiología , Inhibición Prepulso/efectos de los fármacos , Animales , Masculino , Microinyecciones , Ratas Wistar , Receptor de Serotonina 5-HT2A/fisiología , Ritanserina/administración & dosificación , Agonistas del Receptor de Serotonina 5-HT2/administración & dosificación , Antagonistas del Receptor de Serotonina 5-HT2/administración & dosificaciónRESUMEN
INTRODUCTION: Salicylate at high doses induces tinnitus in humans and experimental animals. However, the mechanisms and loci of action of salicylate in inducing tinnitus are still not well known. The expression of Immediate Early Genes (IEG) is traditionally associated with long-term neuronal modifications but it is still not clear how and where IEGs are activated in animal models of tinnitus. OBJECTIVES: Here we investigated the expression of c-fos and Egr-1, two IEGs, in the Dorsal Cochlear Nucleus (DCN), the Inferior Colliculus (IC), and the Posterior Ventral Cochlear Nucleus (pVCN) of rats. METHODS: Rats were treated with doses known to induce tinnitus in rats (300mg/kg i.p. daily, for 3 days), and c-fos and Egr-1 protein expressions were analyzed using western blot and immunocytochemistry. RESULTS: After administration of salicylate, c-fos protein expression increased significantly in the DCN, pVCN and IC when assayed by western blot. Immunohistochemistry staining showed a more intense labeling of c-fos in the DCN, pVCN and IC and a significant increase in c-fos positive nuclei in the pVCN and IC. We did not detect increased Egr-1 expression in any of these areas. CONCLUSION: Our data show that a high dose of salicylate activates neurons in the DCN, pVCN and IC. The expression of these genes by high doses of salicylate strongly suggests that plastic changes in these areas are involved in the genesis of tinnitus.
Asunto(s)
Núcleo Coclear/efectos de los fármacos , Regulación de la Expresión Génica/efectos de los fármacos , Genes Inmediatos-Precoces/efectos de los fármacos , Colículos Inferiores/efectos de los fármacos , Salicilatos/farmacología , Animales , Western Blotting , Relación Dosis-Respuesta a Droga , Proteína 1 de la Respuesta de Crecimiento Precoz/efectos de los fármacos , Genes fos/efectos de los fármacos , Masculino , Ratas , Ratas Wistar , Salicilatos/administración & dosificaciónRESUMEN
OBJECTIVES: To assess the incidence of testicular appendices (Tas), epididymal anomalies (EAs), and processus vaginalis (PV) patency in patients with undescended testis (UT) according to testicular position and to compare them with human fetuses. METHODS: We studied 85 patients (108 testes) with cryptorchidism and compared the features with those of 15 fetuses (30 testes) with scrotal testes. We analyzed the relationships among the testis and epididymis, patency of PV, and the presence of TAs. We used the Chi-square test for statistical analysis (p < 0.05). RESULTS: In 108 UT, 72 (66.66%) had PV patent, 67 (62.03%) had TAs, and 39 (36.12%) had EAs. Of the 108 UT, 14 were abdominal (12.96%; 14 had PV patency, 9 TAs, and 7 EAs); 81 were inguinal (75%; 52 had PV patency, 45 TAs, and 31 EAs), and 13 were suprascrotal (12.03%; 6 had PV patency, 13 TAs, and 1 EAs). The patency of PV was more frequently associated with EAs (p = 0.00364). The EAs had a higher prevalence in UT compared with fetuses (p = 0.0005). CONCLUSIONS: Undescended testis has a higher risk of anatomical anomalies and the testes situated in abdomen and inguinal canal have a higher risk of presenting patency of PV and EAs.
Asunto(s)
Criptorquidismo/fisiopatología , Epidídimo/anomalías , Peritoneo/anomalías , Testículo/anomalías , Niño , Preescolar , Epidídimo/fisiopatología , Feto , Humanos , Lactante , Colículos Inferiores/anomalías , Colículos Inferiores/fisiopatología , Conducto Inguinal/anomalías , Conducto Inguinal/fisiopatología , Masculino , Peritoneo/fisiopatología , Factores de Riesgo , Hidrocele Testicular/fisiopatología , Testículo/fisiopatologíaRESUMEN
It has been shown that electrical stimulation of the mesencephalic tectum (MT) provokes defensive responses in both humans and rodents. During an emotional aversive state, some convergent studies have also demonstrated the existence of a complex interaction between endogenous opioid peptide- and γ-aminobutyric acid (GABA)-containing connections during fear-induced responses. It has been proposed that opioid neurons exert an influence on GABAergic interneurons, which, in turn, exert inhibitory tonic control on the mesencephalic excitatory pathways. Thus, opioid peptides can disinhibit neurons that are tonically inhibited by GABA, therefore, modulating the expression of defensive behavioural reactions. In the present work, we used both electric stimulation and microinjections of the GABAA receptor antagonist bicuculline in the inferior colliculus (IC) of Wistar rats in combination with microinjections of µ- and κ-opioid receptor selective agonists into the dorsal columns of periaqueductal grey matter (dPAG) to evaluate the effects on panic-like behaviours elicited by IC electrical and chemical stimulation. The present results showed that neurochemical lesions of the dPAG caused a significant impairment in the organisation of defensive responses by IC neurons, reducing the duration [t(14)=3.0; p<0.01] of defensive immobility and the duration [t(14)=2.8; p<0.05] and frequency [t(14)=2.5; p<0.05] of escape. Paradoxically, treating the dPAG with the µ-opioid receptor agonist met-enkephalin caused a significant reduction of panic-like behaviours induced by both electrical and chemical stimulation of the IC, increasing the escape behaviour threshold [F(2,23)=13.5; p<0.001] and decreasing the frequency [F(3,36)=11.7; p<0.001] and duration [F(3,36)=11.6; p<0.001] of escape and the duration of defensive immobility [F(3,36)=16.1; p<0.05]. In contrast, treating the dPAG with the κ-opioid receptor agonist salvinorin-A increased the frequency [F(3,36)=12.4; p<0.01] and duration [F(3,34)=16.1; p<0.01] of defensive immobility induced by GABAA receptor blockade in the IC. The present results suggest the existence of a complex neuronal network in the MT in which endogenous opioid peptides and GABAergic pathways interact in the control of fear-related behavioural responses.
Asunto(s)
Analgésicos Opioides/farmacología , Colículos Inferiores/fisiología , Pánico/fisiología , Sustancia Gris Periacueductal/fisiología , Receptores Opioides kappa/metabolismo , Receptores Opioides mu/metabolismo , Animales , Bicuculina/farmacología , Diterpenos de Tipo Clerodano/farmacología , Estimulación Eléctrica , Encefalina Metionina/farmacología , Reacción de Fuga/fisiología , Reacción Cataléptica de Congelación/fisiología , Antagonistas de Receptores de GABA-A/farmacología , Ácido Iboténico , Colículos Inferiores/efectos de los fármacos , Masculino , Neuronas/efectos de los fármacos , Neuronas/fisiología , Sustancia Gris Periacueductal/efectos de los fármacos , Ratas Wistar , Receptores de GABA-A/metabolismo , Receptores Opioides kappa/agonistas , Receptores Opioides mu/agonistasRESUMEN
The phylum Myxozoa Grassé, 1970, consists of a heterogenous group of around 50 genera that are worldwide disseminated in a wide variety of aquatic media. In the present study, 43 specimens of Pimelodus ornatus were collected from an adjacent area to the Cachoeira do Arari municipality on Marajó Island, in the Brazilian state of Pará, in 2013. Macroscopic analysis showed the presence of whitened plasmodia located in the cardiac muscle and also in the region between the bulbus arteriosus and atrium cordis. Microscopic analysis on the parasitized tissues revealed spores that were typically piriform, with the anterior portion slightly narrower than the posterior end. The spore valves were symmetrical. The present species is placed in the genus Myxobolus Butschli, 1882, because of the presence of a pair of equal polar capsules in each spore. The prevalence of parasitism observed was 13.9% (6/43). This research note reports the first occurrence of Myxobolus as a parasite of the heart in the teleostean fish P. ornatus in the Amazon region and confirms the occurrence of secondary myocarditis in this fish, caused by parasitism by Myxobolus sp. The rarity of this parasitic species of Myxobolus at this tissue site, associated with other spore morphology characteristics in the fish, suggests that it is an undescribed species.
O filo Myxozoa Grassé, 1970, consiste em um grupo heterogêneo de cerca de 50 gêneros que são disseminados em todo o mundo em uma grande variedade de meios aquáticos. No presente estudo, quarenta e três espécimes de Pimelodus ornatus foram coletados a partir de uma área adjacente à cidade de Cachoeira do Arari, na Ilha do Marajó, no Estado do Pará, em 2013. À análise macroscópica verificou-se a presença de plasmódios esbranquiçados, localizados no músculo cardíaco e também na região entre o bulbus arteriosus e o atrium cordis. A análise microscópica dos tecidos parasitados revelou esporos que eram tipicamente piriformes, com a porção anterior um pouco mais estreita do que a extremidade posterior, sendo suas válvulas simétricas. A prevalência do parasitismo observada foi de 13,9% (6/43). Esta nota de pesquisa relata a primeira ocorrência de Myxobolus como um parasita do coração no peixe teleósteo P. ornatus, na Região Amazônica e, confirma a ocorrência de miocardite secundária causada por esse parasitismo. A raridade da ocorrência de Myxobolus sp. neste tecido, associado a outras características morfológicas dos esporos no peixe, sugere que é uma espécie não descrita.
Asunto(s)
Animales , Percepción Auditiva/fisiología , Quirópteros/fisiología , Colículos Inferiores/fisiología , Estimulación Acústica , Ecolocación , Potenciales Evocados Auditivos del Tronco Encefálico , Neuronas/fisiología , Vocalización AnimalRESUMEN
The phylum Myxozoa Grassé, 1970, consists of a heterogenous group of around 50 genera that are worldwide disseminated in a wide variety of aquatic media. In the present study, 43 specimens of Pimelodus ornatus were collected from an adjacent area to the Cachoeira do Arari municipality on Marajó Island, in the Brazilian state of Pará, in 2013. Macroscopic analysis showed the presence of whitened plasmodia located in the cardiac muscle and also in the region between the bulbus arteriosus and atrium cordis. Microscopic analysis on the parasitized tissues revealed spores that were typically piriform, with the anterior portion slightly narrower than the posterior end. The spore valves were symmetrical. The present species is placed in the genus Myxobolus Butschli, 1882, because of the presence of a pair of equal polar capsules in each spore. The prevalence of parasitism observed was 13.9% (6/43). This research note reports the first occurrence of Myxobolus as a parasite of the heart in the teleostean fish P. ornatus in the Amazon region and confirms the occurrence of secondary myocarditis in this fish, caused by parasitism by Myxobolus sp. The rarity of this parasitic species of Myxobolus at this tissue site, associated with other spore morphology characteristics in the fish, suggests that it is an undescribed species.
O filo Myxozoa Grassé, 1970, consiste em um grupo heterogêneo de cerca de 50 gêneros que são disseminados em todo o mundo em uma grande variedade de meios aquáticos. No presente estudo, quarenta e três espécimes de Pimelodus ornatus foram coletados a partir de uma área adjacente à cidade de Cachoeira do Arari, na Ilha do Marajó, no Estado do Pará, em 2013. À análise macroscópica verificou-se a presença de plasmódios esbranquiçados, localizados no músculo cardíaco e também na região entre o bulbus arteriosus e o atrium cordis. A análise microscópica dos tecidos parasitados revelou esporos que eram tipicamente piriformes, com a porção anterior um pouco mais estreita do que a extremidade posterior, sendo suas válvulas simétricas. A prevalência do parasitismo observada foi de 13,9% (6/43). Esta nota de pesquisa relata a primeira ocorrência de Myxobolus como um parasita do coração no peixe teleósteo P. ornatus, na Região Amazônica e, confirma a ocorrência de miocardite secundária causada por esse parasitismo. A raridade da ocorrência de Myxobolus sp. neste tecido, associado a outras características morfológicas dos esporos no peixe, sugere que é uma espécie não descrita.