Chronic Toxoplasma gondii infection contributes to perineuronal nets impairment in the primary somatosensory cortex.

Toxoplasma gondii is able to manipulate the host immune system to establish a persistent and efficient infection, contributing to the development of brain abnormalities with behavioral repercussions. In this context, this work aimed to evaluate the effects of T. gondii infection on the systemic inflammatory response and structure of the primary somatosensory cortex (PSC). C57BL/6 and BALB/c mice were infected with T. gondii ME49 strain tissue cysts and accompanied for 30 days. After this period, levels of cytokines IFN-γ, IL-12, TNF-α and TGF-ß were measured. After blood collection, mice were perfused and the brains were submitted to immunohistochemistry for perineuronal net (PNN) evaluation and cyst quantification. The results showed that C57BL/6 mice presented higher levels of TNF-α and IL-12, while the levels of TGF-ß were similar between the two mouse lineages, associated with the elevated number of tissue cysts, with a higher occurrence of cysts in the posterior area of the PSC when compared to BALB/c mice, which presented a more homogeneous cyst distribution. Immunohistochemistry analysis revealed a greater loss of PNN labeling in C57BL/6 animals compared to BALB/c. These data raised a discussion about the ability of T. gondii to stimulate a systemic inflammatory response capable of indirectly interfering in the brain structure and function.

Prenatal exposure to fluoxetine modulates emotionality and aversive memory in male and female rat offspring.

During pregnancy, women are prone to depression, for which selective serotonin reuptake inhibitors (SSRIs), such as fluoxetine, are usually the first-line treatment. However, fluoxetine can cross the placental barrier and affect fetuses, causing changes in serotonin levels early in life. Long-term effects in the brain circuits that control cognitive and emotional behavior are related to early fluoxetine exposure during development. In this study, we aimed to investigate whether fluoxetine exposure (10 mg/kg/day) from the 13th gestational day (GD13) to GD21 may lead to behavioral emotional-cognitive changes in male and female rat offspring approximately 90 days postnatally (~PN90). We have analyzed the performance of individuals in the open field and in the plus-maze discriminative avoidance task, which assesses anxiety and learning/memory processing behaviors. We have found that prenatal (GD13-GD21) exposure to fluoxetine strengthened aversive memory and induced higher anxiety levels in males, and quick extinction of aversive memory in females. Taken together, these results suggest that early exposure to fluoxetine impairs the basal state of anxiety and the cognitive functions of rats during adulthood, which may be in a sex-specific manner because males appear more susceptible than females.

Neuroinflammation in early, late and recovery stages in a progressive parkinsonism model in rats.

Parkinson's disease (PD) is characterized by motor and non-motor signs, which are accompanied by progressive degeneration of dopaminergic neurons in the substantia nigra. Although the exact causes are unknown, evidence links this neuronal loss with neuroinflammation and oxidative stress. Repeated treatment with a low dose of reserpine-inhibitor of VMAT2-has been proposed as a progressive pharmacological model of PD. The aim of this study was to investigate whether this model replicates the neuroinflammation characteristic of this disease. Six-month-old Wistar rats received repeated subcutaneous injections of reserpine (0.1 mg/kg) or vehicle on alternate days. Animals were euthanized after 5, 10, or 15 injections, or 20 days after the 15th injection. Catalepsy tests (motor assessment) were conducted across treatment. Brains were collected at the end of each treatment period for immunohistochemical and RT-PCR analyzes. Reserpine induced a significant progressive increase in catalepsy duration. We also found decreased immunostaining for tyrosine hydroxylase (TH) in the substantia nigra pars compacta (SNpc) and increased GFAP + cells in the SNpc and dorsal striatum after 10 and 15 reserpine injections. Phenotyping microglial M1 and M2 markers showed increased number of CD11b + cells and percentage of CD11b + /iNOS + cells in reserpine-treated animals after 15 injections, which is compatible with tissue damage and production of cytotoxic factors. In addition, increased CD11b + /ArgI + cells were found 20 days after the last reserpine injection, together with an increment in IL-10 gene expression in the dorsal striatum, which is indicative of tissue repair or regeneration. Reserpine also induced increases in striatal interleukin TNF-alpha mRNA levels in early stages. In view of these results, we conclude that reserpine-induced progressive parkinsonism model leads to neuroinflammation in regions involved in the pathophysiology of PD, which is reversed 20 days after the last injection. These findings reveal that withdrawal period, together with the shift of microglial phenotypes from the pro-inflammatory to the anti-inflammatory stage, may be important for the study of the mechanisms involved in reversing this condition, with potential clinical applicability.

Sex differences in the acute ethanol effects on object recognition memory: influence of estrous cycle.

Effects of acute ethanol (EtOH) on memory depend on several factors, including type of behavioral task. Sex differences in EtOH effects have been reported in humans and animals, and recognition memory can be influenced by circulating sex hormones. The aim of this study was to investigate the influence of sex and estrous cycle in the acute effects of EtOH on novel object recognition memory in rats. Male and female Wistar rats were part of one of the groups: control, 0.6-g/kg EtOH and 1.8-g/kg EtOH (administered intraperitoneally before the training session). The estrous cycle was evaluated by vaginal smear. The task was conducted in an open field arena. During training, animals were exposed to two identical objects, and test sessions were performed 1 h (short-term) and 24 h (long-term) later. One of the objects was changed in each test. Increased novel object exploration was shown by male and female controls in the short- and long-term tests, respectively. In the short-term test, females did not show preference for the novel object, and EtOH 1.8 g/kg impaired performance in males. In the long-term test, both sexes showed object discrimination, and 1.8-g/kg EtOH reduced preference for the new object in male rats. The phase of the cycle, the performance on proestrus was worse compared with other phases, and EtOH failed to impair performance mainly on estrous. In conclusion, while male rats displayed ethanol-induced recognition memory deficit, female rats were unaffected by EtOH impairing effects. In addition, the performance of female rats was influenced by the estrous cycle phases.

Effects of prenatal exposure to fluoxetine on circadian rhythmicity in the locomotor activity and neuropeptide Y and 5-HT expression in male and female adult Wistar rats.

Serotonin (5-HT) reuptake inhibitors, such as fluoxetine, are the most prescribed antidepressant for maternal depression. In this sense, it exposes mothers and the brains of infants to increased modulatory and trophic effects of serotonergic neurotransmission. 5-HT promotes essential brain changes throughout its development, which include neuron migration, differentiation and organisation of neural circuitries related to emotional, cognitive and circadian behavior. Early exposure to the SSRIs induces long-term effects on behavioral and neural serotonergic signalisation. We have aimed to evaluate the circadian rhythm of locomotor activity and the neurochemical content, neuropeptide Y (NPY) and 5-HT in three brain areas: intergeniculate leaflet (IGL), suprachiasmatic nuclei (SCN) and raphe nuclei (RN), at two zeitgebers (ZT6 and ZT18), in male and female rat's offspring early exposed (developmental period GD13-GD21) to fluoxetine (20 mg/kg). First, we have conducted daily records of the locomotor activity rhythm using activity sensors coupled to individual cages over 4 weeks. We have lastly evaluated the immunoreactivity of NPY in both SCN and IGL, as well the 5-HT expression in the dorsal and medial RN. In summary, our results showed that (1) prenatal fluoxetine affects phase entrainment of the rest/activity rhythm at ZT6 and ZT18, more in male than female specimens, and (2) modulates the NPY and 5-HT expression. Here, we show male rats are more susceptible to phase entrainment and the NPY and 5-HT misexpression compared to female ones. The sex differences induced by early exposure to fluoxetine in both the circadian rhythm of locomotor activity and the neurochemical expression into SCN, IGL and midbrain raphe are an important highlight in the present work. Thus, our results may help to improve the knowledge on neurobiological mechanisms of circadian rhythms and are relevant to understanding the "broken brains" and behavioral abnormalities of offspring early exposed to antidepressants.

Female Rats Are Resistant to Cognitive, Motor and Dopaminergic Deficits in the Reserpine-Induced Progressive Model of Parkinson's Disease.

Parkinson's disease (PD) is the second most common neurodegenerative disease. The main symptoms are motor signs such as resting tremor and difficulty in initializing movements. Non-motor alterations, such as cognitive deficits, can precede the motor symptoms. PD is more frequent in men than women. The mechanisms related to this difference are not completely understood. There is evidence that females present distinct characteristics in dopaminergic function compared to males. While the severity of motor impairments is often compared between sexes, little is known about sex differences in the prodromal stage. Most animal models of PD present acute severe motor impairment, which precludes the study of non-motor symptoms. Our research group have proposed an adaptation of the classic reserpine protocol, using low doses in a chronic treatment. This method allows the observation of progressive motor impairment as well as premotor deficits. Here we investigate possible behavioral and neuronal sex differences in the effects of the repeated treatment with a low dose of reserpine in rats. Male and female Wistar rats received 10-15 injections of reserpine (0.1 mg/kg) or vehicle, on alternate days. We followed-up the estrous cycle phases and conducted motor and cognitive assessments (catalepsy, open field, oral movements and object recognition tests). The euthanasia occurred 48 h after the 10th or 15th injections, with the collection of blood for the quantification of sex hormones and brains for tyrosine hydroxylase (TH) immunohistochemistry in the substantia nigra pars compact (SNpc). Reserpine induced progressive catalepsy, involuntary oral movements and cognitive deficits in male rats. The behavioral effects of reserpine were attenuated (motor) or absent (cognitive) in females. Reserpine decreased TH immunoreactivity in males, but not in females. Estrogen levels in females negatively correlated with catalepsy duration. Our findings show that females present a delay and/or a prevention in the reserpine-induced motor alterations in the progressive PD model, compatible with the lower prevalence of this disease in women. Further, females were protected from the deficit in object recognition at the prodromal stage. The absence of reserpine-induce decrease in TH immunoreactivity suggests that differences in dopaminergic function/plasticity are related to this protection in female sex.

Postnatal exposure to fluoxetine led to cognitive-emotional alterations and decreased parvalbumin positive neurons in the hippocampus of juvenile Wistar rats.

The exposure to selective serotonin reuptake inhibitors (SSRIs) during development results in behavioural impairment in adulthood in humans and animal models. Indeed, serotonergic overexpression in early life leads to structural and functional changes in brain circuits that control cognition and emotion. However, the effects of developmental exposure to these substances on the behaviour of adolescent rats are conflicting and remain poorly characterised. We performed a behavioural screening to investigate the effects of postnatal exposure to fluoxetine on memory and behaviours related to anxiety, anhedonia, and depression, as well we evaluate the parvalbumin expression in hippocampus of juvenile (~PND45) female and male rats. Fluoxetine (daily 20 mg/kg s.c. injections from PND7-PND21)- or vehicle-treated adolescent rats went through several behavioural tasks (from PND 38 to PND52) and were subject to transcardial perfusion and brain removal for immunohistochemical analysis (PND53). We found that postnatal exposure to fluoxetine increased anxiety- and depression-like behaviours in the open field and sucrose preference and forced swimming tests, respectively. In addition, this treatment induced working memory and short-term (but not long-term) recognition memory impairments, and reduced parvalbumin-positive interneurons in the hippocampus. In addition, the results revealed developmental sex-dependent effects of fluoxetine postnatal treatment on adolescent rats' behaviour. These outcomes indicate that affective disorders and mnemonic alterations caused by SSRIs perinatal exposure can be present at adolescence.

Changes in the mesocorticolimbic pathway after low dose reserpine-treatment in Wistar and Spontaneously Hypertensive Rats (SHR): Implications for cognitive deficits in a progressive animal model for Parkinson's disease.

Reserpine (RES) is an irreversible inhibitor of VMAT2 used to study Parkinson's disease (PD) and screening for antiparkinsonian treatments in rodents. Recently, the repeated treatment with a low dose of reserpine was proposed as a model capable of emulating progressive neurochemical, motor and non-motor impairments in PD. Conversely, compared to Wistar rats, Spontaneously Hypertensive Rats (SHR) are resistant to motor changes induced by repeated treatment with a low dose of RES. However, such resistance has not yet been investigated for RES-induced non-motor impairments. We aimed to assess whether SHR would have differential susceptibility to the object recognition deficit induced by repeated low-dose reserpine treatment. We submitted male Wistar and SHR rats to repeated RES treatment (15 s.c. injections of 0.1 mg/kg, every other day) and assessed object memory acquisition and retrieval 48 h after the 6th RES injection (immediately before the appearance of motor impairments). Only RES Wistar rats displayed memory impairment after reserpine treatment. On the other hand, untreated SHR rats displayed object recognition memory deficit, but RES treatment restored such deficits. We also performed immunohistochemistry for tyrosine hydroxylase (TH) and α-synuclein (α-syn) 48 h after the last RES injection. In a different set of animals submitted to the same treatment, we quantified DA, 5-HT and products of lipid peroxidation in the prefrontal cortex (PFC) and hippocampus (HPC). SHR presented increased constitutive levels of DA in the PFC and reduced immunoreactivity to TH in the medial PFC and dorsal HPC. Corroborating the behavioral findings, RES treatment restored those constitutive alterations in SHR. These findings indicate that the neurochemical, molecular and genetic differences in the SHR strain are potentially relevant targets to the study of susceptibility to diseases related to dopaminergic alterations.

Nociception alterations precede motor symptoms in a progressive model of parkinsonism induced by reserpine in middle-aged rats.

Nociception alterations are frequent non-motor symptoms of the prodromal phase of Parkinson's disease (PD). The period for the onset of symptoms and the pathophysiological mechanisms underlying these alterations remain unclear. We investigated the course of nociception alterations in a progressive model of parkinsonism induced by reserpine (RES) in rats. Male Wistar rats (6-7 months) received 5 or 10 subcutaneous injections of RES (0.1 mg/kg) or vehicle daily for 20 days. Motor evaluation and nociceptive assessment were performed throughout the treatment. At the end of the treatment rats were euthanized, the brains removed and processed for immunohistochemical analysis (TH and c-Fos). The RES-treated rats exhibited an increased nociceptive response to mechanical and chemical stimulation in the electronic von Frey and formalin tests, respectively. Moreover, these alterations preceded the motor impairment observed in the catalepsy test. In addition, the RES treatment reduced the TH-immunoreactivity in the ventral tegmental area (VTA) and increased the c-Fos expression in the ventral-lateral periaqueductal gray (vlPAG), rostral ventral medulla (RVM) and dorsal raphe nucleus (DRN) after noxious stimuli induced by formalin. Taken together, our results reinforce that nociceptive changes are one of the early signs of PD and monoamine depletion in basal ganglia can be involved in the abnormal processing of nociceptive information in PD.

Impaired discriminative avoidance and increased plasma corticosterone levels induced by vaginal lavage procedure in rats.

Historically, females have been neglected in behavioral neuroscience research due to the alleged increased variability caused by hormonal fluctuations. More recently, there has been a tendency to include female subjects in the studies, in a majority of those cases with the condition that the hormonal variation is controlled. In rodent studies, the vaginal lavage procedure is a common method of collecting smears and determining the estrous cycle phase. However, little is known regarding the consequences of the procedure, although stress is often mentioned as a concern. Within the neuroscience field, spatial memory has been a relevant subject in terms of sex differences. The plus-maze discriminative avoidance task (PMDAT) allows for the concomitant evaluation of spatial memory, anxiety-like behavior, and locomotion, as well as possible interactions between these behaviors. The aim of the present study was to investigate the effects of the vaginal lavage procedure (VLP) on the performance of female rats in the  PMDAT. We submitted adult female Wistar rats to VLP for 14 straight days and then to training and test sessions in the PMDAT. Additionally, another set of animals was submitted to the VLP procedure for determination of plasma corticosterone levels. Rats submitted to the vaginal lavage procedure did not discriminate the enclosed arms of the PMDAT apparatus, indicating impaired performance, but no anxiety-like alterations were found. VLP also resulted in a higher corticosterone level, suggesting it is a stressful manipulation. As such, the use of this method to control for hormonal variation should be restricted in behavioral studies.

Changes in the mesocorticolimbic pathway after low dose reserpine-treatment in Wistar and Spontaneously Hypertensive Rat (SHR): implications for cognitive deficits in a progressive animal model for Parkinson’s Disease

Reserpine (RES) is an irreversible inhibitor of VMAT2 used to study Parkinson’s disease (PD) and screening for antiparkinsonian treatments in rodents. Recently, the repeated treatment with a low dose of reserpine was proposed as a model capable of emulating progressive neurochemical, motor and non-motor impairments in PD. Conversely, compared to Wistar rats, Spontaneously Hypertensive Rats (SHR) are resistant to motor changes induced by repeated treatment with a low dose of RES. However, such resistance has not yet been investigated for RES-induced non-motor impairments. We aimed to assess whether SHR would have differential susceptibility to the object recognition deficit induced by repeated low-dose reserpine treatment. We submitted male Wistar and SHR rats to repeated RES treatment (15 s.c. injections of 0.1 mg/kg, every other day) and assessed object memory acquisition and retrieval 48 h after the 6th RES injection (immediately before the appearance of motor impairments). Only RES Wistar rats displayed memory impairment after reserpine treatment. On the other hand, untreated SHR rats displayed object recognition memory deficit, but RES treatment restored such deficits. We also performed immunohistochemistry for tyrosine hydroxylase (TH) and α-synuclein (α-syn) 48 h after the last RES injection. In a different set of animals submitted to the same treatment, we quantified DA, 5-HT and products of lipid peroxidation in the prefrontal cortex (PFC) and hippocampus (HPC). SHR presented increased constitutive levels of DA in the PFC and reduced immunoreactivity to TH in the medial PFC and dorsal HPC. Corroborating the behavioural findings, RES treatment restored those constitutive alterations in SHR. These findings indicate that the neurochemical, molecular and genetic differences in the SHR strain are potentially relevant targets to the study of susceptibility to diseases related to dopaminergic alterations.

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.

Are There Multiple Motivators for Helping Behavior in Rats?

Empathy is the ability to (a) be affected by and share the emotional state of another; (b) assess the reasons for the other's state; and (c) identify with the other, adopting their perspective. This phenomenon has been shown to exist in several species and is proposed as a motivator for prosocial behavior. The experimental study of this feature in laboratory rodents is a more viable alternative in comparison to wild animals. A recent report showed that rats opened a door to free their cage mate from a restraint box. Although this behavior has been suggested to be motivated by empathy, this fact has been questioned by several studies that proposed other motivators for the releasing behavior. In the present study, we use an adaptation of the protocol of releasing behavior to investigate aspects of empathy and pro-sociality such as familiarity and reciprocity. In addition, we addressed some potential motivational factors that could influence this behavior. The main results showed that (1) rats opened the restraint box to free conspecifics most of the time; (2) direct reciprocity or past restriction experience did not improve releasing performance, probably due to a ceiling effect; (3) after a series of trials in the presence of a restricted conspecific, the free rat continues to open the restraint box even if it is empty; (4) in general, the opening performance improves across trials and phases, resembling learning curves; (5) if the first series of trials occurs with the empty box, the opening behavior does not occur and is modest in subsequent trials with a trapped animal; (6) the exploratory drive toward the restraint box and desire for social contact do not seem to function as key motivators for releasing behavior. In conclusion, our findings do not support that the opening behavior is exclusively related to empathic motivation. While multiple factors might be involved, our study suggests that task learning triggered (and possibly reinforced) by the presence of the restricted rat can function as a motivator. Further investigations are required to fully understand the mechanisms and motivation factors guiding the releasing behavior.

Short-term but not long-term exposure to an enriched environment facilitates the extinction of aversive memory.

Environmental enrichment (EE) has been used to investigate behavioral changes and neuroplasticity in brain in normal and pathological conditions. Besides, the EE has been used to understand the neurobehavioral systems involved in learning experiences, visual inputs, defensive responses, social interactions and memory. However, the required exposure duration to remove aversive memories remains lacking. Therefore, the purpose of the present study was to investigate the time-course effect of EE exposure on the extinction of aversive memory. Young adult male Wistar rats were exposed to two different EE protocols: short-term environmental enrichment (EE2 - animal kept under enriched conditions for two weeks) and long-term environmental enrichment (EE4 - animal kept under enriched conditions for four weeks). The contextual fear conditioning test was used to assess aversive memory. The both EE protocols provide changes in Zif-268 immunoreactivity in mesocorticolimbic areas such as CA1 and central amygdala; however, only short-term EE reduces the ZIF-268 immunoreactivity in VTA. Besides, both EE protocols also provide an increase in TH immunoreactivity in VTA and nucleus accumbens, but only the short-term EE modifies the TH immunoreactivity in CA1 and infralimbic region of the prefrontal cortex. The time-course effect of EE interferes differently on the extinction of aversive memory, being two weeks of exposure with EE sufficient to cause improvement in coping during aversive situations, favoring the extinction of conditioned fear memory.

Genetic polymorphism in IL17RA induces susceptibility to Toxoplasma gondii infection in Brazilian pregnant women.

Congenital toxoplasmosis is a parasitic disease caused by Toxoplasma gondii, an obligate intracellular parasite which can cause fetal death/abortion and can induce damage in the brain and eyes of the infected babies. The environmental and genetic factors associated with T. gondii and the maternal immune response, drive part of the pathogenesis of congenital toxoplasmosis. Thus, in this study, we aimed to investigate the allelic and genotypic frequencies of specific single nucleotide polymorphisms (SNPs) in the IL17A and IL17RA genes, as well as the production of IL-17A, IL-33, and CCL2 in pregnant women, from the State of Rio Grande do Norte, Brazil, further relating these along with the clinical parameters, to the toxoplasmosis infection. Through PCR-RFLP techniques, two SNPs implicated in Th17 immune response, IL17A rs2275913 (G> A) and IL17RA rs4819554 (A> G) modulation were evaluated in pregnant women, either infected or not infected by T. gondii. These women were also evaluated in terms of plasma release of CCL2, IL-33, and IL-17A which relate to hypertension, number of abortions, and ethnic pattern. The results showed that the G-allele of the SNP rs2275913 (IL17A) appeared to be protective in this population, while the rs4819554 (IL17RA) SNP G allele was associated with greater susceptibility to T. gondii infection [ρ value = 0.025; OR = 2.815 (1.118-7.089); CI = 95%]. None of the cytokines had any influence on the analyzed parameters (abortion and hypertension). In conclusion, our data suggest an immunogenic evidence of susceptibility to T. gondii infection driven by the rs4819554 (IL17RA) SNP G allele in Brazilian pregnant women. Further studies are needed to reinforce this trial marker in populations from distinct geographical areas as well as to confirm the protective pattern related to the G-allele of the SNP rs2275913 (IL17A) in pregnant women.

Chronic Toxoplasma gondii infection contributes to decreasing of perineuronal nets surrounding neurons in the Corpus striatum of mice.

Recent advances in chronic toxoplasmosis understanding became the focus of discussion about behavioral abnormalities, which could be explained by cyst location and neuronal impairment in specific brain areas. Perineuronal nets (PNNs) are specialized extracellular matrices that surround the neuronal body and proximal dendrites and play key roles in neuronal circuitry maintenance and stabilization. Its impairment can lead to abnormal synaptic functioning with behavioral repercussions. In this context, we analyzed the impact of Toxoplasma gondii infection on neuronal integrity in the Corpus striatum of chronically infected mice. C57BL/6 and Balb/c female mice were infected with T. gondii ME49 cysts. Brain sections were submitted to immunohistochemistry with Wisteria floribunda agglutinin (WFA) for PNN labeling followed by quantification of tissue cyst and labeled neuronal cells 30 days after infection. Our results revealed that C57BL/6 exhibited a significant decrease in PNN-positive (WFA+) labeled neurons and an expressively higher number of tissue cysts than Balb/c mice. It was also possible to observe that the number of T. gondii tissue cysts and the number of WFA+ neurons were inversely correlated for C57BL/6-infected mice. However, no correlation was observed for Balb/c mice. These data suggest how the impact of parasite dissemination in the brain and host characteristics can influence neuronal integrity impairment during infection by decreasing WFA+ neurons. This might be a plausible pathway in which the presence of T. gondii contributes to behavioral changes in the infected host.

Conspecific Presence Improves Episodic-Like Memory in Rats.

A number of studies have provided evidence that animals, including rats, remember past episodes. However, few experiments have addressed episodic-like memory from a social perspective. In the present study, we evaluated Wistar rats in the WWWhen/ELM task as single setups and in dyads, applying a long retention interval. We also investigated behaviors that could subserve the emergence of this type of memory. We found that only rats tested in the social setting were able to recollect an integrated episodic-like memory that lasted 24 h. Additionally, rats in dyads presented higher levels of exploration during the task. When exposed to the testing environment, the dyads exhibited affiliative behavior toward each other and presented fewer anxiety-like responses. Our findings indicate that the presence of a conspecific could act as a facilitating factor in memory evaluations based on spontaneous exploration of objects and provide empirical support for applying more naturalistic settings in investigations of episodic-like memory in rats.

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.

Serotonergic dysfunction in a model of parkinsonism induced by reserpine.

Parkinson's disease (PD) is mainly characterized by a dopamine deficiency accompanied by structural and functional changes in striatal neuronal projections. However, studies have considered PD as a multi-systemic disease in which the neurodegenerative process extends beyond the dopaminergic system. Therefore, the purpose of the present study was to investigate the time-course of serotonergic neuron damage in a progressive model of parkinsonism induced by a low dose of reserpine. Thus, male Wistar rats received 4 (ST, short-treatment of reserpine) or 10 (MT, middle-term treatment of reserpine) subcutaneous injections of vehicle or reserpine (0.1 mg/kg) at a volume of 1 mL/kg body weight, on alternate days. Animals were euthanized 48 h after the last injection for immunohistochemical analysis. After ST, 5-HT immunoreactivity decreased in hippocampal subareas (CA1 and CA3) and medial prefrontal cortex (mPFC) compared to vehicle. Furthermore, animals MT-treated also showed progressive decrease of 5-HT immunoreactivity in CA1 and CA3 subareas. Conversely, a significant increase of 5-HT immunoreactivity was found in mPFC and dorsal raphe nucleus (DRN) in animals submitted to MT when compared to ST exposure. The results showed that, in the repeated low-dose reserpine rat model, variations in the immunoreactivity of 5-HT start early in the course of progressive parkinsonism.

Episodic-like memory impairment induced by sub-anaesthetic doses of ketamine.

Episodic-like memory refers to integration of where and when a certain event (what) happened. The glutamatergic neurotransmission, particularly AMPA and NMDA receptors, in the dorsal hippocampus mediates episodic recall. Ketamine is a non-competitive NMDA antagonist with effect on cognitive performance and plasticity. The goal of this study was to evaluate the acute action of ketamine on behavioural and neurochemical aspects of episodic-like memory (WWWhen/ELM task) through immediate-early gene expression (IEG), c-Fos, in the dorsal hippocampus. Animals received saline 0.9% or ketamine at 8 mg/kg or 15 mg/kg (i.p.) immediately after the second sample. Our data indicate that untreated and saline rats integrate the three elements of episodic-like memory. Conversely, animals treated with ketamine showed impairment of ELM formation. In addition, the highest dose of ketamine increased c-Fos expression in dorsal CA1 subregion when compared to saline rats. Our results indicate that the antagonism of NMDA concurrently impair ELM formation of all three aspects of ELM and increase neuronal activation in dorsal CA1.