Esper A. Cavalheiro

Temporal lobe epilepsy and social behavior: An animal model for autism?

Social behavior depends on the integrity of social brain circuitry. The temporal lobe is an important part of the social brain, and manifests morphological and functional alterations in autism spectrum disorders (ASD). Rats with temporal lobe epilepsy (TLE), induced with pilocarpine, were subjected to a social discrimination test that has been used to investigate potential animal models of ASD, and the results were compared with those for the control group. Rats with TLE exhibited fewer social behaviors than controls. No differences were observed in nonsocial behavior between groups. The results suggest an important role for the temporal lobe in regulating social behaviors. This animal model might be used to explore some questions about ASD pathophysiology.

Biophysical Aspects of the Nonsynaptic Epileptiform Activity

Since the demonstration that the hippocampus slice exposed to low calcium external solution is able to sustain nonsynaptic epileptiform activity, it has been accepted that nonsynaptic interactions may be sufficient, in some conditions, for generating seizure like activity in cortical network. Recently, evidences have suggested that the reductions in calcium are not essential for nonsynaptic mechanisms to contribute to epileptic activity. Therefore, evidences allow demonstrating that the conjoint actuation of nonsynaptic mechanisms and nonsynaptic connections are able to induce and sustain seizures. The nonsynaptic mechanisms considered in this context are all mechanisms which are not directly involved with synaptic transmission, but comprehending important action on the homeostasis equilibrium and, consequently, on the neuronal excitability. The non-synaptic connections are all types of neuronal coupling that are not mediated by synaptic transmission. The concomitant actuation of nonsynaptic mechanisms and connections seems to be a relevant process for the seizure intensity modulation. Therefore, it may be conjectured that the nonsynaptic mechanisms and connections could be considered a natural target for investigations aiming to control refractory seizures. Within this perspective, the scope of the present chapter will cover the following topics: • nonsynaptic events: experimental induction and electrophysiological characteristics; • nonsynaptic mechanisms; • nonsynaptic connections; • biophysical aspects of the nonsynaptic epileptiform activities; • possible targets for controlling refractory seizures.

Thalamic nuclear abnormalities as a contributory factor in sudden cardiac deaths among patients with schizophrenia.

Patients with schizophrenia have a two- to three-fold increased risk of premature death as compared to patients without this disease. It has been established that patients with schizophrenia are at a high risk of developing cardiovascular disease. Moreover, an important issue that has not yet been explored is a possible existence of a “cerebral” focus that could trigger sudden cardiac death in patients with schizophrenia. Along these lines, several structural and functional alterations in the thalamic complex are evident in patients with schizophrenia and have been correlated with the symptoms manifested by these patients. With regard to abnormalities on the cellular and molecular level, previous studies have shown that schizophrenic patients have fewer neuronal projections from the thalamus to the prefrontal cortex as well as a reduced number of neurons, a reduced volume of either the entire thalamus or its subnuclei, and abnormal glutamate signaling. According to the glutamate hypothesis of schizophrenia, hypofunctional corticostriatal and striatothalamic projections are directly involved in the pathophysiology of the disease. Animal and post-mortem studies have provided a large amount of evidence that links the sudden unexpected death in epilepsy (SUDEP) that occurs in patients with schizophrenia and epilepsy to thalamic changes. Based on the results of these prior studies, it is clear that further research regarding the relationship between the thalamus and sudden cardiac death is of vital importance.