Toxoplasma gondii infection damages the perineuronal nets in a murine model

BACKGROUND Behavioral and neurochemical alterations associated with toxoplasmosis may be influenced by the persistence of tissue cysts and activation of an immune response in the brain of Toxoplasma gondii-infected hosts. The cerebral extracellular matrix is organised as perineuronal nets (PNNs) that are both released and ensheath by some neurons and glial cells. There is evidences to suggest that PNNs impairment is a pathophysiological mechanism associated with neuropsychiatric conditions. However, there is a lack of information regarding the impact of parasitic infections on the PNNs integrity and how this could affect the host's behavior. OBJECTIVES In this context, we aimed to analyse the impact of T. gondii infection on cyst burden, PNNs integrity, and possible effects in the locomotor activity of chronically infected mice. METHODS We infected mice with T. gondii ME-49 strain. After thirty days, we assessed locomotor performance of animals using the open field test, followed by evaluation of cysts burden and PNNs integrity in four brain regions (primary and secondary motor cortices, prefrontal and somesthetic cortex) to assess the PNNs integrity using Wisteria floribunda agglutinin (WFA) labeling by immunohistochemical analyses. FINDINGS AND MAIN CONCLUSIONS Our findings revealed a random distribution of cysts in the brain, the disruption of PNNs surrounding neurons in four areas of the cerebral cortex and hyperlocomotor behavior in T. gondii-infected mice. These results can contribute to elucidate the link toxoplasmosis with the establishment of neuroinflammatory response in neuropsychiatric disorders and to raise a discussion about the mechanisms related to changes in brain connectivity, with possible behavioral repercussions during chronic T. gondii infection.

Sensory involvement in the SOD1-G93A mouse model of amyotrophic lateral sclerosis

A subset of patients of amyotrophic lateral sclerosis (ALS) present with mutation of Cu/Zn superoxide dismutase 1 (SOD1), and such mutants caused an ALS-like disorder when expressed in rodents. These findings implicated SOD1 in ALS pathogenesis and made the transgenic animals a widely used ALS model. However, previous studies of these animals have focused largely on motor neuron damage. We report herein that the spinal cords of mice expressing a human SOD1 mutant (hSOD1-G93A), besides showing typical destruction of motor neurons and axons, exhibit significant damage in the sensory system, including Wallerian-like degeneration in axons of dorsal root and dorsal funiculus, and mitochondrial damage in dorsal root ganglia neurons. Thus, hSOD1-G93A mutation causes both motor and sensory neuropathies, and as such the disease developed in the transgenic mice very closely resembles human ALS.

Calcium-influx increases SOD1 aggregates via nitric oxide in cultured motor neurons

Familial amyotrophic lateral sclerosis (fALS) is caused by mutations in Cu/Zn-superoxide dismutase (SOD1), and SOD1 aggregation and calcium toxicity are involved in neuronal death. However, the effect of altered calcium homeostasis on the SOD1 aggregation is unknown. To investigate whether calcium triggers mutant SOD1 aggregation in vitro, human mutant SOD1 (G93A) was transfected into motor neuronal cell line (VSC 4.1 cells). These cells were then treated with calcium ionophore A23187 or agents that induce intracellular calcium release like cyclic ADP ribose, ryanodine or thapsigargin. A23187 was found to increase mutant SOD1 aggregation and neuronal nitric oxide synthase (nNOS) expression. Moreover, the NOS inhibitor (L-NAME) and a NO-dependent cyclic GMP cascade inhibitor (ODQ) reduced SOD1 aggregation, whereas an exogenous NO donor (GSNO) increased mutant SOD1 aggregation, which was also prevented by NOS or cGMP cascade inhibitor. Our data demonstrate that calcium-influx increases SOD1 aggregation by upregulating NO in cultured motor neuronal cells.

Guillain-Barre syndrome in children and adolescents--a retrospective analysis.

In this study, 55 cases of Guillain-Barre syndrome (GBS) in children and adolescents of 2-18 years of age were analysed retrospectively to study the clinical profile and to evaluate the prognostic value of reduced compound muscle action potential (CMAP) on the need for ventilation and functional outcome. Of the 28 boys and 27 girls 87.3% were bed-bound at peak deficit. Other features were as follows: Bifacial weakness-75%, bulbar weakness-56.4%, need for assisted ventilation-41.8% and albuminocytological dissociation-65.9%. In the ventilated and non-ventilated group no difference was noted in the incidence of reduced CMAP amplitude (p-value > 0.5). At 3 months 83.3% and at 6 months 80.8% cases were ambulant with support. Reduced CMAP amplitude of less than 20% of the lower limit of the normal in at least 2 nerves did not predict the need for ventilation or the chance of independent walking at 3 or 6 months.

A inibição da COMT no tratamento da doença de Parkinson / The inhibition of COMT in the treatment of Parkinson's disease

A doença de Parkinson idiopática (DP) é um dos problemas neurológicos mais frequentes. Apesar de ainda não ter cura, existem numerosos recursos para obter controle sintomático prolongado. Entre as drogas existentes, os inibidores da catecol-O-metiltransferase (COMT), como adjuntivas à levodopa, se constituem em importante opção terapêutica dessa doença. A presente revisão tem por objetivo apresentar os fundamentos neurobiológicos, principalmente em relação ao metabolismo da dopamina em condições normais e patológicas, assim como as características dos inibidores da COMT. Espera-se que uma melhor compreensão da ação desse grupo de drogas, permita sua utilização mais adequada, visando melhor controle das manifestações típicas da doença em suas diversas fases, assim como prevenir ou atenuar as frequentemente incapacitantes complicações motoras.

Phenyldiguanide activates cardiac receptors to produce responses by involving three different efferent pathways in anaesthetized rats.

The present study was undertaken to determine the afferent and efferent pathways involved in the phenyldiguanide (PDG)-induced reflex response in rats. Intravenous (iv) injection of PDG (10 microg/kg), produced hypotension, bradycardia and apnea over a period of time. Bilateral vagotomy abolished the PDG-induced reflex changes. Atropine (2 mg/kg; iv) blocked only the bradycardiac response produced by PDG, while prazosin (0.5 mg/kg; iv) blocked the hypotensive response, and bilateral vagotomy in these animals abolished the apneic response. In separate series of experiments, intrapericardial injection of lignocaine abolished the hypotensive and bradycardiac responses evoked by PDG in artificially ventilated rats. The results reveal that the PDG-induced reflex is mediated through vagal afferents originating from the heart and efferents involve three different pathways. The bradycardiac response was through the muscarinic receptors, the hypotension is mediated through alpha1 adrenoceptors and the apnea presumably through the spinal motoneurones supplying the respiratory muscles.