Possible connection between latent toxoplasmosis and schizophrenia is a very interesting and medically important topic. In this thesis I tried to map current state of knowledge in the interdisciplinary research of schizophrenia and Toxoplasma gondii and their possible connections as well as to show differences in responses between Toxoplasma-positive and Toxoplasma-negative subjects using simple computer-administered tests of prepulse inhibition of startle reaction (PPI). Such differences would suggest another similarity between schizophrenia patients and subjects with latent toxoplasmosis as the sensorimotor gating responsible for PPI was found to be disrupted in schizophrenia patients. Side goal of the study was to test newly developed PC software for testing PPI and to determine its applicability in further research. Subjects for the tests were recruited among adepts of professional military service; 409 subjects completed the test of acoustic PPI and 276 subjects completed the test of visual PPI. All the subjects were tested on presence of specific anti-Toxoplasma IgG in their blood serum. Both tests revealed significant (p<0.001) differences between responses on prepulse-preceded stimuli and plain stimuli without prepulse, no significant results were, however, gained for the effects of latent...

Effects of Toxoplasmosis on Reaction Times and Prepulse Inhibition of Startle Reaction in Humans vi Abstract Toxoplasma gondii, a single-cell coccidia from almost exclusively parasitic phylum Apicomplexa, does not typically cause acute health issues in humans with most exceptions among immunodeficient individuals and pregnant mothers or, more precisely, their offspring. In the latent phase, the bradyzoites in tissue cysts placed most often in neural and muscle tissues can evolve pressure on the host's body both as a collateral effect of the presence of the parasitic organism in host's tissues and as a consequence of adaptive evolution leading to increase in probability of trophic transmission to the final host, a felid. In humans, this can result in slight changes in personality profiles, deterioration of psychomotor and cognitive functions, and development of serious mental disorders. The thesis focuses predominantly on one of the aspects of the changes, namely the effect of latent toxoplasmosis on the processing of startle signals themselves and when modified by a preceding low-intensity signal; this processing may be connected with the development of schizophrenia in predisposed individuals. Studies conducted within the project framework found changes int the speed of signal processing in...

Recent studies have shown elevated neuroinflammation in a large subset of individuals diagnosed with schizophrenia. A pro-inflammatory cytokine, tumor necrosis factor-alpha (TNFα), has been directly linked to this neuroinflammation. This study examined the effects of two TNFα modulators (PD2024 and PD340) produced by our collaborators at P2D Bioscience, Inc., to alleviate auditory sensorimotor gating deficits and reduce microglial cell activation present in the polyinosinic:polycytidylic (Poly I:C) rodent model of schizophrenia. Auditory sensorimotor gating was assessed using prepulse inhibition and microglial activation was examined and quantified using immunohistochemistry and confocal microscopy, respectively. Both PD2024 and PD340 alleviated auditory sensorimotor gating deficits and reduced microglia activation and thereby demonstrated the ability to treat both the behavioral and neuroinflammatory aspects of the disorder. These results are significant and suggest that neural TNFα is a potential pharmacological target for the treatment of schizophrenia.

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Une des théories actuellement prépondérante pour expliquer le déclin cognitif observé chez les personnes âgées est une perte généralisée de la fonction inhibitrice. En revanche, de plus en plus d’études révèlent un maintien et même un gain sur le plan émotionnel chez les âgés. Afin de caractériser l’effet de l’âge sur la fonction inhibitrice et sur les émotions, nous avons utilisé le paradigme bien connu du réflexe acoustique de sursaut et de son inhibition par le prépulse, un phénomène reconnu comme reflétant le filtrage sensorimoteur, soit une mesure pré-attentionnelle d’inhibition. Le réflexe acoustique de sursaut est une réponse du corps tout entier à un bruit fort et inattendu et a été mesuré via la magnitude et la latence du clignement des yeux. La présentation d’un son faible (prépulse) quelques millisecondes avant le bruit de sursaut réduit la réponse de sursaut. Deux groupes de participants (jeunes adultes et âgés) ont visionné des images plaisantes, neutres et déplaisantes issues du International Affective Picture System (IAPS), lesquelles étaient associées à des stimuli auditifs évaluant le réflexe acoustique de sursaut et son inhibition par le prépulse. Les résultats démontrent que le réflexe de sursaut est modulé différemment par les émotions chez les jeunes adultes et les âgés. Plus particulièrement, les adultes âgés ont un plus grand réflexe de sursaut que les jeunes adultes lorsqu’ils visionnent des images plaisantes et neutres. Le processus d’inhibition par le prépulse est également modulé différemment par les émotions chez les âgés et les jeunes adultes: les âgés ont une plus grande inhibition du réflexe de sursaut que les jeunes adultes lorsqu’ils visionnent des images plaisantes et déplaisantes, mais ils ne diffèrent pas des jeunes adultes pour les images neutres. Dans l’ensemble, les résultats obtenus ne sont pas compatibles avec une perte d’inhibition chez les adultes âgés, et supportent plutôt un biais émotionnel positif. / Aging is often characterized by a decline in cognitive abilities and a loss of inhibitory function. At the same time there is promising, yet limited to date, evidence of a better emotion regulation with aging. In order to characterize the effect of age on inhibitory function and emotions, in this study the well-known acoustic startle paradigm and its inhibition by a prepulse, a phenomenon known to engage sensorimotor gating, were used. The acoustic startle reflex, a whole-body reflex in response to a loud and unexpected sound, was measured through eye blink magnitude and latency. The inhibition of this acoustic startle response by the presentation of a weak sound, a prepulse, was also measured. Two groups of 30 adults (young and older adults) viewed pleasant, neutral, and unpleasant images from the International Affective Picture System (IAPS) while startle and prepulse trials were presented. The results show that the startle response is differently modulated in the two groups, with the elderly displaying a greater startle reflex while viewing pleasant and neutral pictures compared to young adults. Prepulse inhibition is also differently modulated by emotions in young adults and their older counterparts, with the latter exhibiting a greater inhibition of the startle reflex when viewing pleasant and unpleasant pictures (but not for neutral pictures) compared to young adults. In summary, the present data do not support a decline of the inhibitory function with increasing age, but rather support a positivism effect.

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