Periodic weakness of the diaphragm as the sole manifestation of bulbar onset myasthenia.

No abstract provided.

Enhanced nonsynaptic epileptiform activity in the dentate gyrus after kainate-induced status epilepticus.

Understanding the mechanisms that influence brain excitability and synchronization provides hope that epileptic seizures can be controlled. In this scenario, non-synaptic mechanisms have a critical role in seizure activity. The contribution of ion transporters to the regulation of seizure-like activity has not been extensively studied. Here, we examined how non-synaptic epileptiform activity (NEA) in the CA1 and dentate gyrus (DG) regions of the hippocampal formation were affected by kainic acid (KA) administration. NEA enhancement in the DG and suppression in area CA1 were associated with increased NKCC1 expression in neurons and severe neuronal loss accompanied by marked glial proliferation, respectively. Twenty-four hours after KA, the DG exhibited intense microglial activation that was associated with reduced cell density in the infra-pyramidal lamina; however, cellular density recovered 7 days after KA. Intense Ki67 immunoreactivity was observed in the subgranular proliferative zone of the DG, which indicates new neuron incorporation into the granule layer. In addition, bumetanide, a selective inhibitor of neuronal Cl(-) uptake mediated by NKCC1, was used to confirm that the NKCC1 increase effectively contributed to NEA changes in the DG. Furthermore, 7 days after KA, prominent NKCC1 staining was identified in the axon initial segments of granule cells, at the exact site where action potentials are preferentially initiated, which endowed these neurons with increased excitability. Taken together, our data suggest a key role of NKCC1 in NEA in the DG.

Morphological and electrophysiological properties of pyramidal-like neurons in the stratum oriens of Cornu ammonis 1 and Cornu ammonis 2 area of Proechimys.

Proechimys (Rodentia: Echimyidae) is a neotropical rodent of the Amazon region that has been successfully colonized in the laboratory and used for experimental medicine. Preliminary studies indicated that Proechimys (casiragua) rodents express an atypical resistance to developing a chronic epileptic condition in common models of temporal lobe epilepsy. Moreover, previous investigation of our laboratory described a remarkably different Proechimy's cytoarchitecture organization of the hippocampal CA2 subfield. In the present study, we investigated the intrinsic neuronal properties and morphological characteristics of the Proechimys's hippocampal pyramidal neurons of the CA1 and CA2 areas. A comparative approach was performed using neurons recorded in Wistar rats. A striking finding in Proechimys rodents was the presence of large pyramidal-like neurons throughout the stratum oriens from CA2 to CA1 area. In order to confirm such distinctive feature of the Proechimys's hippocampus, we performed Nissl staining and immunohistochemistry for neurofilament protein SM311. CA2 pyramidal neurons in the stratum pyramidale of Proechimys exhibited a significantly higher input resistance and lower time constant when compared to corresponding cell groups in the same area of the Wistar rat's. This newly identified population of pyramidal-shaped neurons in stratum oriens of Proechimys exhibited distinct electrophysiological and morphological properties. This included larger capacitance, lower input resistance, larger rheobase, long latency to first action potential and slower firing frequency. In addition, the apical dendrites of these neurons were oriented in parallel to apical dendrites of regular pyramidal neurons in stratum pyramidale. Moreover, these neurons were immunoreactive to SM311 as the majority of the neurons of the pyramidal layer. The functional role of these hippocampal neurons of the rodent Proechimys deserves further investigation.

Distinctive hippocampal CA2 subfield of the Amazon rodent Proechimys.

Previous data of our laboratory have shown that the Amazonian rodents Proechimys do not present spontaneous seizures in different models of epilepsy, suggesting endogenous inhibitory mechanisms. Here, we describe a remarkably different Proechimy's cytoarchitecture organization of the hippocampal cornu Ammonis 2 (CA2) subfield. We identified a very distinctive Proechimy's CA2 sector exhibiting disorganized cell presentation of the pyramidal layer and atypical dispersion of the pyramidal-like cells to the stratum oriens, strongly contrasting to the densely packed CA2 cells in the Wistar rats. Studies showed that CA2 is the only cornu ammonis (CA) subfield resistant to the extensive pyramidal neural loss in mesial temporal lobe epilepsy (MTLE) associated to hippocampal sclerosis. Thus, in order to investigate this region, we used Nissl and Timm staining, stereological approach to count neurons and immunohistochemistry to neuronal nuclei (NeuN), parvalbumin (PV), calbindin (CB) and calretinin (CR). We did not notice statistically significant differences in the total number of neurons of the CA2 region between Proechimys and Wistar. However, Proechimys rodents presented higher CA2 volume than Wistar rats. Furthermore, no significant difference in the optical density of parvalbumin-immunoreactivity was found between subject groups. On the other hand, Proechimys presented significant higher density of calbindin and calretinin-immunoreactivity when compared to Wistar rats. In this context, this unique CA2 subfield seen in Proechimys opens up a new set of possibilities to explore the contribution of CA2 neurons in normal and pathological brain circuits.

Early life handling decreases serotonin turnover in the nucleus accumbens and affects feeding behavior of adult rats.

In our previous studies, we reported that neonatally handled rats have an increased ingestion of sweet food but are resistant to the damaging effects of a chronic exposure to a highly palatable diet. Accumbal serotonin (5-HT) is important for feeding behavior and plays a role in the vulnerability to diet-induced obesity. Therefore, our hypotheses were (1) 5-HT turnover in the nucleus accumbens is altered in neonatally handled animals and plays a role in their differential feeding behavior and (2) if this is so, a chronic pharmacological treatment affecting 5-HT reuptake (chronic imipramine) would be able to revert the behavioral findings. Litters were divided into nonhandled and handled (10 min/day, Days 1-10 after birth). In Experiment 1, we demonstrated that a decreased 5-HT metabolism in the nucleus accumbens was observed in adult handled animals. In Experiment 2, the two previous groups were subdivided and assigned to receive imipramine diluted in water or water alone. After 30 days of treatment, we evaluated their weight gain and feeding behavior. Handled rats weighed less than nonhandled rats, and all imipramine-treated rats showed a reduction in weight gain after 60 days of treatment. Imipramine reverted the increased sweet food consumption seen in neonatally handled rats. We conclude that serotonin is involved in the altered feeding behavior of neonatally handled rats, and this protocol is an important tool for studying the mechanisms by which early life events have a long-term impact on feeding preferences.

Early life experience alters behavioral responses to sweet food and accumbal dopamine metabolism.

Neonatal handling in rats persistently alters behavioral parameters and responses to stress. Such animals eat more sweet food in adult life, without alterations in lab chow ingestion. Here, we show that neonatally handled rats display greater incentive salience to a sweet reward in a runway test; however they are less prone to conditioned place preference and show less positive hedonic reactions to sweet food. When injected with methylphenidate (a dopamine mimetic agent), non-handled rats increase their sweet food ingestion in the fasted state, while neonatally handled rats do not respond. We did not observe any differences regarding baseline general ambulatory activity between the groups. A lower dopamine metabolism in the nucleus accumbens was observed in handled animals, without differences in norepinephrine content. We suggest that early handling leads to a particular response to positive reinforcers such as palatable food, in a very peculiar fashion of higher ingestion but lower hedonic impact, as well as higher incentive salience, but diminished dopaminergic metabolism in the nucleus accumbens.

Seizure occurrence in patients with chronic renal insufficiency in regular hemodialysis program

Hemodialysis-associated seizure is a complication of hemodialysis. This report describes the occurrence of seizures in patients with end stage renal disease on dialysis therapy at the Nephrology Institute of Mogi das Cruzes, São Paulo State, Brazil. A retrospective medical history of 189 patients was reviewed to investigate the occurrence of convulsive seizures during dialytic program. Seven patients with history of seizures were selected but five of them were included in our study. Three patients presented generalized tonic-clonic seizures, one had partial seizure with secondary generalization, and one presented unclassified seizure. Three patients presented seizure just during the dialysis (unique seizure) and one of them presented convulsive status epilepticus. The two other patients had already presented seizures prior the beginning of dialysis. We conclude that seizures in renal failure could be considered as occasional events that do not usually become chronic.

Convulsões durante o tratamento dialítico podem constituir uma complicação da hemodiálise. Esse artigo descreve a ocorrência de crises em pacientes em estágio final de insuficiência renal crônica sob tratamento dialítico no Instituto de Nefrologia de Mogi das Cruzes, São Paulo, Brasil. Foram revistos os prontuários de 189 pacientes, com o objetivo de investigar a ocorrência de crises convulsivas durante o tratamento dialítico. Dos sete pacientes selecionados com história de crises, cinco concordaram em participar de nosso estudo. Três pacientes apresentaram crises generalizadas tônico-clônicas, um apresentou crise parcial com generalização subseqüente e um apresentou crise inclassificada. Três pacientes apresentaram crises apenas durante o processo dialítico (crise única) sendo que um deles apresentou status epilepticus convulsivo. Os outros dois pacientes já haviam apresentado crises antes do início do tratamento dialítico. Nós concluímos que as crises convulsivas que ocorrem em pacientes com falência renal podem ser consideradas como eventos ocasionais e que usualmente não se tornam crônicas.

Expression of nestin in the hippocampal formation of rats submitted to the pilocarpine model of epilepsy.

Nestin is an embryonic intermediate filament component protein, transiently expressed by the immediate precursor cells of neurons and glia, during brain development. We studied the nestin distribution in the hippocampal formation of rats submitted to pilocarpine model of epilepsy. Animals were studied during the acute, silent and chronic phases. Rats from control and acute groups presented absence of nestin-immunoreactivity (IR) in the hippocampal cells. In contrast, cells from this region presented strong nestin IR during the silent phase (3 and 7 days after status epilepticus (SE) onset), disappearing 14 days after SE. Nestin IR cells were scattered expressed in all hippocampal formation during the chronic phase. Almost all nestin IR cells exhibited glial fibrillary acidic protein (GFAP), which seems to revert to a more primitive glial form, as part of an adaptive response, transiently re-expressing phenotypic features typical of earlier stages of glial development. The re-expression of this developmental protein in the damaged cerebral tissue suggests that nestin may play an important role in the reconstruction of the glial cytoskeleton and/or remodeling events occurring in the pilocarpine model of epilepsy. Understanding how astrocytes influence network function in the injured hippocampus may, therefore, provide insight into epileptogenic mechanisms.

p-Methylthioamphetamine and 1-(m-chlorophenyl)piperazine, two non-neurotoxic 5-HT releasers in vivo, differ from neurotoxic amphetamine derivatives in their mode of action at 5-HT nerve endings in vitro.

The mechanism underlying the serotoninergic neurotoxicity of some amphetamine derivatives, such as p-chloroamphetamine (pCA) and 3,4-methylenedioxymethamphetamine (MDMA), is still debated. Their main acute effect, serotonin (5-HT) release from nerve endings, involves their interaction with 5-HT transporters (SERTs), as substrates. Although this interaction is required for the neurotoxic effects, 5-HT release alone may not be sufficient to induce long-term 5-HT deficits. Some non-neurotoxic compounds, including p-methylthioamphetamine (MTA) and 1-(m-chlorophenyl)piperazine (mCPP), have 5-HT releasing properties in vivo and in brain slices comparable to that of neurotoxic amphetamine derivatives. We measured 5-HT release in superfused rat brain synaptosomes preloaded with [3H]5-HT, a model that distinguishes a releasing effect from reuptake inhibition. MTA and mCPP induced much lower release than pCA and MDMA. The striking difference between our findings in synaptosomes and those obtained in vivo or in brain slices is probably related to a different compartmentalisation of 5-HT in the different experimental models. Studies in synaptosomes, where the vesicular storage of 5-HT is predominant, could therefore bring to light differences between neurotoxic and non-neurotoxic 5-HT releasing agents which cannot be appreciated in other experimental models and might be useful to identify the mechanisms responsible for the neurotoxicity induced by amphetamine derivatives.

ALEPH-2, a suspected anxiolytic and putative hallucinogenic phenylisopropylamine derivative, is a 5-HT2a and 5-HT2c receptor agonist.

To assess the pharmacodynamic profile of ALEPH-2, a phenylisopropylamine derivative with alleged anxiolytic and hallucinogenic properties, Xenopus laevis oocytes were microinjected with either of the rat cRNA for the 5-HT2A or the 5-HT2C receptor. Concentration-response curves were obtained following the exposure of the oocytes to varying concentrations of either ALEPH-2 or 5-hydroxytryptamine (5-HT) for 10 s. ALEPH-2 is a partial agonist on the 5-HT2A receptor with a similar potency to 5-HT. In contrast, ALEPH-2 is a full 5-HT2C receptor agonist and is about 15-fold less potent than 5-HT. Pre-application of 1 microM ritanserin antagonized the responses induced by 5-HT and ALEPH-2 to the same extent; however, the 5-HT2A receptor is more sensitive to ritanserin blockade than the 5-HT2C receptor.