Terminal Arbors of Callosal Axons Undergo Plastic Changes in Early-Amputated Rats.

Sensory information is processed in specific brain regions, and shared between the cerebral hemispheres by axons that cross the midline through the corpus callosum. However, sensory deprivation usually causes sensory losses and/or functional changes. This is the case of people who suffered limb amputation and show changes of body map organization within the somatosensory cortex (S1) of the deafferented cerebral hemisphere (contralateral to the amputated limb), as well as in the afferented hemisphere (ipsilateral to the amputated limb). Although several studies have approached these functional changes, the possible finer morphological alterations, such as those occurring in callosal axons, still remain unknown. The present work combined histochemistry, single-axon tracing and 3D microscopy to analyze the fine morphological changes that occur in callosal axons of the forepaw representation in early amputated rats. We showed that the forepaw representation in S1 was reduced in the deafferented hemisphere and expanded in the afferented side. Accordingly, after amputation, callosal axons originating from the deafferented cortex undergo an expansion of their terminal arbors with increased number of terminal boutons within the homotopic representation at the afferented cerebral hemisphere. Similar microscale structural changes may underpin the macroscale morphological and functional phenomena that characterize limb amputation in humans.

Experimental Granulomatous Amebic Encephalitis Caused by Acanthamoeba castellanii.

Acanthamoeba genus can affect humans with diseases such as granulomatous amebic encephalitis (GAE), a highly lethal neuroinfection. Several aspects of the disease still need to be elucidated. Animal models of GAE have advanced our knowledge of the disease. This work tested Wistar rats (Rattus norvegicus albinus) as an animal model of GAE. For this, 32 animals were infected with 1 × 106A. castellanii trophozoites of the T4 genotype. Ameba recovery tests were carried out using agar plates, vascular extravasation assays, behavioral tests, and histopathological technique with H/E staining. Data were subjected to linear regression analysis, one-way ANOVA, and Tukey's test, performed in the GraphPad Prism® 8.0 program, with a significance level of p < 0.05. The results revealed the efficiency of the model. Amebae were recovered from the liver, lungs, and brain of infected animals, and there were significant encephalic vascular extravasations and behavioral changes in these animals, but not in the control animals. However, not all infected animals showed positive histopathology for the analyzed organs. Nervous tissues were the least affected, demonstrating the role of the BBB in the defense of the CNS. Supported by the demonstrated evidence, we confirm the difficulties and the feasibilities of using rats as an animal model of GAE.

Neuroprotective effects of crude extracts, compounds, and isolated molecules obtained from plants in the central nervous system injuries: a systematic review.

The number of people with central nervous system (CNS) injuries increases worldwide and only a few therapies are used to mitigate neurological damage. Crude extracts, compounds, and isolated molecules obtained from plants have neuroprotective effects; however, their actions on the central nervous system are still not fully understood. This systematic review investigated the neuroprotective effects of crude extracts, compound, and isolated molecules obtained from plants in different CNS lesions. This PICO (Population/Problem, Intervention, Control, Outcome) systematic review included in vivo and in vitro studies that used small rodents as experimental models of CNS injuries (P) treated with crude extracts, compounds, and/or isolated molecules obtained from plants (I), compared to non-intervention conditions (C), and that showed a neuroprotective effect (O). Fourteen out of 5,521 studies were selected for qualitative analysis. Several neuroprotective effects (improvement of antioxidant activity, modulation of the inflammatory response, tissue preservation, motor and cognitive recovery) in the brain and spinal cord were reported after treatment with different doses of crude extracts (10 studies), compounds (2 studies), and isolated molecules (2 studies). Crude extracts, compounds, or isolated molecules obtained from plants showed promising neuroprotective effects against several CNS injuries in both the brain and spinal cord, regardless of gender and age, through the modulation of inflammatory activity and oxidative biochemistry, tissue preservation, and recovery of motor and cognitive activity.

Physical activity based on dance movements as complementary therapy for Parkinson's disease: Effects on movement, executive functions, depressive symptoms, and quality of life.

BACKGROUND: Parkinson's disease (PD) is a progressive, neurodegenerative disease with motor symptoms that are well understood, but non-motor symptoms may be present and appear at different temporal stages of the disease. Physical activity based on dance movements is emerging as a complementary therapeutic approach to a range of PD symptoms as a multidimensional activity that requires rhythmic synchronization and more neuromuscular functions. OBJECTIVE: To evaluate the effects of physical activity based on dance movements on the movement, executive functions, depressive symptoms, quality of life, and severity of PD in individuals diagnosed with PD. METHODS: 13 individuals with PD (Hoehn & Yahr I-III, MDS-UPDRS 67.62 ± 20.83), underwent physical activity based on dance movements (2x week for 6 months). Participants were assessed at baseline and after 6 months on movement (POMA, TUG and MDS-UPDRS Part III), executive function (FAB), depressive symptoms (MADRS), quality of life (PDQ-39), and severity of PD (MDS-UPDRS TOTAL). Student's t-test was used to compare pre and post-intervention results. RESULTS: We observed a significant improvement in the movement (balance and gait) by the POMA test, p = 0.0207, executive function by the FAB test, p = 0.0074, abstract reasoning and inhibitory control by the FAB, Conceptualization test, p = 0.0062, and Inhibitory Control, p = 0.0064, depressive symptoms assessed by the MADRS test significantly reduced, p = 0.0214, and the quality of life by the PDQ-39 had a significant increase after the intervention, p = 0.0006, showed significant improvements between the pre-and post-intervention periods of physical activity based on dance movements. CONCLUSION: Physical activity based on dance movements contributed to significant improvements in movement (balance and gait), executive functions, especially in cognitive flexibility and inhibitory control, and the quality of life too. Sensorimotor integration, most cognitive processing and social skills may have contributed to the results. TRIAL REGISTRATION: The study was registered in the Brazilian registry of clinical trials: RBR-3bhbrb5.

Time Window of the Critical Period for Neuroplasticity in S1, V1, and A1 Sensory Areas of Small Rodents: A Systematic Review.

The plasticity of the central nervous system (CNS) allows the change of neuronal organization and function after environmental stimuli or adaptation after sensory deprivation. The so-called critical period (CP) for neuroplasticity is the time window when each sensory brain region is more sensitive to changes and adaptations. This time window is usually different for each primary sensory area: somatosensory (S1), visual (V1), and auditory (A1). Several intrinsic mechanisms are also involved in the start and end of the CP for neuroplasticity; however, which is its duration in S1, VI, and A1? This systematic review evaluated studies on the determination of these time windows in small rodents. The careful study selection and methodological quality assessment indicated that the CP for neuroplasticity is different among the sensory areas, and the brain maps are influenced by environmental stimuli. Moreover, there is an overlap between the time windows of some sensory areas. Finally, the time window duration of the CP for neuroplasticity is predominant in S1.

High performance liquid chromatography-based method to analyze activity of GABA transporters in central nervous system.

The GATs are the membrane proteins responsible for the uptake of GABA in the central nervous system. Alterations in GAT activity are implicated in several neurological diseases, including retinopathies. The present study describes an alternative method to determine GAT activity in tissue preparations of the central nervous system, using high performance liquid chromatography (HPLC) with fluorescence detection. The GABA concentration in the medium was determined using the o-phthaldehyde (OPA)-derivation protocol validated by the Brazilian Health Regulatory Agency (ANVISA) and the United States Food and Drug Administration (US-FDA). The GAT activity in the retinal preparations was determined through the evaluation of the GABA uptake, which was measured by assessing the difference between the initial and final concentrations of GABA in the incubation medium. The evaluation of the GAT kinetics returned values of Km = 382.5 ± 32.2 µM and Vmax = 34 nmol/mg of protein. The data also demonstrated that the GABA uptake was predominantly Na+- and temperature-dependent, and was also inhibited by incubation with nipecotic acid, a substrate of GABA transporters. Taken together, these findings confirm that our approach provided a specific measure of GAT activity in retinal tissue. The data presented here thus validate, for the first time, an alternative, simple and sensitive method for the evaluation of GAT activity using high performance chromatography on preparations of the central nervous system.

Euterpe oleracea fruit (Açai)-enriched diet suppresses the development of experimental cerebral malaria induced by Plasmodium berghei (ANKA) infection.

BACKGROUND: Cerebral malaria is one of the most severe complications attributed to protozoal infection by Plasmodium falciparum, gaining prominence in children mortality rates in endemic areas. This condition has a complex pathogenesis associated with behavioral, cognitive and motor sequels in humans and current antimalarial therapies have shown little effect in those aspects. Natural products with antioxidant and anti-inflammatory properties have become a valuable alternative therapeutic option in the treatment of distinct conditions. In this context, this study investigated the neuroprotective effect of Euterpe oleracea (açai) enriched diet during the development of experimental cerebral malaria induced by the inoculation of Swiss albino mice with Plasmodium berghei ANKA strain. METHODS: After Plasmodium infection, animals were maintained on a feeding with Euterpe oleracea enriched ration and parameters such as survival curve, parasitemia and body weight were routinely monitored. The present study has also evaluated the effect of açai-enriched diet on the blood-brain barrier leakage, histological alterations and neurocognitive impairments in mice developing cerebral malaria. RESULTS: Our results demonstrate that between 7th-19th day post infection the survival rate of the group treated with açai enriched ration was higher when compared with Plasmodium-infected mice in which 100% of mice died until the 11th days post-infection, demonstrating that açai diet has a protective effect on the survival of infected treated animals. The same was observed in the brain vascular extravasation, where Evans blue dye assays showed significantly less dye extravasation in the brains of Plasmodium-infected mice treated with açai enriched ration, demonstrating more preserved blood-brain barrier integrity. Açai-enriched diet also attenuate the histopathological alterations elicited by Plasmodium berghei infection. We also showed a decrease of the neurological impairments arising from the exposure of cerebral parenchyma in the group treated with açai diet, ameliorating motor and neuropsychiatric changes, analyzed through the SHIRPA protocol. CONCLUSION: With these results, we conclude that the treatment with açai enriched ration decreased the mortality of infected animals, as well as protected the blood-brain barrier and the neurocognitive deficits in Plasmodium-infected animals.

Acute Restraint Stress Evokes Anxiety-Like Behavior Mediated by Telencephalic Inactivation and GabAergic Dysfunction in Zebrafish Brains.

Acute stress is an important factor in the development of anxiety disorders. Zebrafish are an organism model widely used by studies that aim to describe the events in the brain that control stress-elicited anxiety. The goal of the current study was to evaluate the pattern of cell activation in the telencephalon of adult zebrafish and the role of the GABAergic system on the modulation of anxiety-like behavior evoked by acute restraint stress. Zebrafish that underwent acute restraint stress presented decreased expression of the c-fos protein in their telencephalon as well as a significant decrease in GABA release. The data also supports that decreased GABA levels in zebrafish brains have diminished the activation of GABAA receptors eliciting anxiety-like behavior. Taken together these findings have helped clarify a neurochemical pathway controlling anxiety-like behavior evoked by acute stress in zebrafish while also opening the possibility of new perspective opportunities to use zebrafish as an animal model to test anxyolitic drugs that target the GABAergic system.

Oxidative Stress Mediates Anxiety-Like Behavior Induced by High Caffeine Intake in Zebrafish: Protective Effect of Alpha-Tocopherol.

Anxiety is a common symptom associated with high caffeine intake. Although the neurochemical mechanisms of caffeine-induced anxiety remain unclear, there are some evidences suggesting participation of oxidative stress. Based on these evidences, the current study is aimed at evaluating the possible protective effect of alpha-tocopherol (TPH) against anxiety-like behavior induced by caffeine (CAF) in zebrafish. Adult animals were treated with CAF (100 mg/kg) or TPH (1 mg/kg)+CAF before behavioral and biochemical evaluations. Oxidative stress in the zebrafish brain was evaluated by a lipid peroxidation assay, and anxiety-like behavior was monitored using light/dark preference and novel tank diving test. Caffeine treatment evoked significant elevation of brain MDA levels in the zebrafish brain, and TPH treatment prevented this increase. Caffeine treatment also induced anxiety-like behavior, while this effect was not observed in the TPH+CAF group. Taken together, the current study suggests that TPH treatment is able to inhibit oxidative stress and anxiety-like behavior evoked by caffeine.

Effect of chronic stress during adolescence in prefrontal cortex structure and function.

Critical periods of plasticity (CPPs) are defined by developmental intervals wherein neuronal circuits are most susceptible to environmental influences. The CPP of the prefrontal cortex (PFC), which controls executive functions, extends up to early adulthood and, like other cortical areas, reflects the maturation of perineuronal nets (PNNs) surrounding the cell bodies of specialized inhibitory interneurons. The aim of the present work was to evaluate the effect of chronic stress on both structure and function of the adolescent's rat PFC. We subjected P28 rats to stressful situations for 7, 15 and 35days and evaluated the spatial distribution of histochemically-labeled PNNs in both the Medial Prefrontal Cortex (MPFC) and the Orbitofrontal Cortex (OFC) and PFC-associated behavior as well. Chronic stress affects PFC development, slowing PNN maturation in both the (MPFC) and (OFC) while negatively affecting functions associated with these areas. We speculate upon the risks of prolonged exposure to stressful environments in human adolescents and the possibility of stunted development of executive functions.

Spatiotemporal distribution of proteoglycans in the developing rat's barrel field and the effects of early deafferentation.

The isolectin Vicia villosa B(4) (VV) selectively recognizes N-acetyl-galactosamine-terminal glycoconjugates that form perineuronal nets (PNNs) around a subset of neurons in the cerebral cortex. PNNs are thought to participate in the guidance of incoming thalamic axons and in the posterior stabilization and maintenance of synaptic contacts. Here we examine the spatial and temporal distribution of biotinylated VV in tangential sections through layer IV of the posteromedial barrel subfield in the primary somatosensory cortex (PMBSF) of rats ranging from postnatal day (P)3 to P60, which underwent unilateral deafferentation of whiskers at birth. In the afferented hemisphere, labeling first appears at P5, with a diffuse distribution, probably associated with neuropil, inside PMBSF barrels. VV distribution remains diffuse during the following week, and declines around P17. From P24 onward, however, proteoglycans form PNNs around cell bodies preferentially localized in septal regions of the PMBSF. In the contralateral, deafferented PMBSF the diffuse labeling also appears on P5, but first develops into elongated, homogeneous stripes, which disappear after P24, leaving only scattered cell bodies along layer IV. Our results indicate that proteoglycans appear simultaneous to barrel formation in the developing rat while segregation of PNNs to septal cells might be driven by afferent activity.