Immune response to Streptococcus pneumoniae in asthma patients: comparison between stable situation and exacerbation.

In Argentina, more than 3 million people suffer from asthma, with numbers rising. When asthma patients acquire viral infections which, in turn, trigger the asthmatic response, they may develop subsequent bacterial infections, mainly by Streptococcus (S.) pneumoniae. This encapsulated Gram(+) bacterium has been considered historically a T cell-independent antigen. Nevertheless, several papers describe the role of T cells in the immune response to S. pneumoniae. We evaluated the response to S. pneumoniae and compared it to the response to Mycobacterium (M.) tuberculosis, a different type of bacterium that requires a T helper type 1 (Th1) response, in cells from atopic asthmatic children, to compare parameters for the same individual under exacerbation and in a stable situation whenever possible. We studied asthma patients and a control group of age-matched children, evaluating cell populations, activation markers and cytokine production by flow cytometry, and cytokine concentration in serum and cell culture supernatants by enzyme-linked immunosorbent assay (ELISA). No differences were observed in γδ T cells for the same patient in either situation, and a tendency to lower percentages of CD4(+) CD25(hi) T cells was observed under stability. A significantly lower production of tumour necrosis factor (TNF)-α and a significantly higher production of interleukin (IL)-5 was observed in asthma patients compared to healthy individuals, but no differences could be observed for IL-4, IL-13 or IL-10. A greater early activation response against M. tuberculosis, compared to S. pneumoniae, was observed in the asthmatic patients' cells. This may contribute to explaining why these patients frequently acquire infections caused by the latter bacterium and not the former.

Dopamine prevents muscarinic-induced decrease of glutamate release in the auditory cortex.

Acetylcholine and dopamine are simultaneously released in the cortex at the occurrence of novel stimuli. In addition to a series of excitatory effects, acetylcholine decreases the release of glutamate acting on presynaptic muscarinic receptors. By recording evoked excitatory postsynaptic currents in layers II/III neurons of the auditory cortex, we found that activation of muscarinic receptors by oxotremorine reduces the amplitude of glutamatergic current (A(oxo)/A(ctr) = 0.53 +/- 0.17) in the absence but not in the presence of dopamine (A(oxo)/A(ctr) = 0.89 +/- 0.12 in 20 microM dopamine). These data suggested that an excessive sensitivity to dopamine, such as postulated in schizophrenia, could prevent the decrease of glutamate release associated with the activation of cholinergic corticopetal nuclei. Thus, a possible mechanism of action of antipsychotic drugs could be through a depression of the glutamatergic signal in the auditory cortex. We tested the capability of haloperidol, clozapine and lamotrigine to affect glutamatergic synaptic currents and their muscarinic modulation. We found that antipsychotics not only work as dopamine receptor antagonists in re-establishing muscarinic modulation, but also directly depress glutamatergic currents. These results suggest that presynaptic modulation of glutamate release can account for a dual route of action of antipsychotic drugs.

[Auditory gating deficits in schizophrenia: unimodal or heteromodal dysfunction?]. / Fallos en el filtraje de información auditiva en esquizofrenia: ¿disfunción de cortezas uni o heteromodales?

Failure filtering out redundant auditory information is the most replicated neurophysiological abnormality observed in patients with schizophrenia. However, the brain structures involved in this deficit remains obscure. Two main hypotheses have been proposed to explain this phenomenon. The first maintains that the auditory gating deficit in schizophrenia is related to abnormal function of microcircuits within the hippocampal formation. The second hypothesis proposes that the deficit may be linked to impaired prefrontal cortex function. In both scenarios, auditory gating is conceptualized as a process dependent on the functional indemnity of cortical areas that integrate information from different sensory modalities. When filtering out redundant information, heteromodal cortices (hippocampal formation or prefrontal cortex), ensure that redundant stimuli do not reach higher-order levels of information processing in the brain and do not interfere with working memory performance. Findings from our lab, using magnetoencephalography (MEG), and data from other labs using electroencephalography (EEG), suggest an alternative hypothesis. We hypothesize that auditory gating deficit in schizophrenia is due to the abnormal function of unimodal microcircuits within left auditory cortex, independent from abnormalities in heteromodal cortices. Explaining whether auditory gating deficit in schizophrenia is determined by a primary dysfunction of unimodal or multimodal cortices may help elucidate the mechanisms involved in the sensory information overload and the characteristic cognitive deficits found in this disorder.