José R. Santos

Molecular, Neurochemical, and Behavioral Hallmarks of Reserpine as a Model for Parkinson's Disease: New Perspectives to a Long-Standing Model

The administration of reserpine to rodents was one of the first models used to investigate the pathophysiology and screening for potential treatments of Parkinsons disease (PD). The reserpine model was critical to the understanding of the role of monoamine system in the regulation of motor and affective disorders, as well as the efficacy of current PD treatments, such as L‐DOPA and dopamine agonists. Nevertheless, with the introduction of toxin‐induced and genetic models of PD, reserpine became underused. The main rationale to this drawback was the supposed absence of reserpine construct validity with PD. Here, we highlight classical and recent experimental findings that support the face, pharmacological, and construct validity of reserpine PD model and reason against the current rationale for its underuse. We also aim to shed a new perspective upon the model by discussing the main challenges and potentials for the reserpine model of PD.

Nutritional status, oxidative stress and dementia: the role of selenium in Alzheimer's disease

The term dementia derives from the Latin demens (“de”: private, “mens”: mind, intelligence, judgment—“without a mind”). The American Psychiatric Association (APA) describes it as “any mental impairment, or global cognitive decline in a previously unimpaired person” and is characterized by a deterioration of cognitive, intellectual, emotional, and behavioral skills, severe enough to interfere with the daily life of its sufferers (APA, 1994). It may be elicited by pathologies related to aging, stroke and mechanical injury, or by recurrent use of alcohol and substance abuse, including smoking (DeKosky et al., 2010; Rojas et al., 2010; Brown and Thore, 2011; Rusanen et al., 2011).

Exposure to an enriched environment facilitates motor recovery and prevents short-term memory impairment and reduction of striatal BDNF in a progressive pharmacological model of parkinsonism in mice

HighlightsRepeated reserpine induces progressive motor damage in mice.Striatal BDNF is decreased in a progressive mouse model of Parkinson’s disease.Enriched environment accelerates motor damage recovery.Enriched environment prevents reserpine‐induced BDNF decrease. ABSTRACT Previous studies showed that the repeated administration with a low dose of reserpine (RES) induces a gradual appearance of motor signs and cognitive deficits compatible with parkinsonism in rodents. Environmental stimulation has neuroprotective effects in animal models of neurodegenerative damage, including acutely induced parkinsonism. We investigated the effects of exposure to an enriched environment (EE) on motor, cognitive and neuronal (levels of tyrosine hydroxylase, TH and brain derived neurotrophic factor, BDNF) deficits induced by a progressive model of Parkinson’s disease (PD) in mice. Male mice were repeatedly treated with vehicle or 0.1 mg/kg of RES (s.c) and kept under two housing conditions: standard environment (SE) and EE. In animals kept in SE, the treatment with RES induced deficits in motor function (catalepsy test, open field and oral movements), in novel object recognition (NOR) and plus‐maze discriminative avoidance tasks. The environmental stimulation facilitated the recovery of motor deficits assessed by the catalepsy test after the end of treatment. Additionally, exposure to EE prevented the memory deficit in the NOR task. Treatment with RES induced a reduction in the number of TH positive cells in SNpc and VTA, which recovered 30 days after the end of treatment. Finally, RES reduced the levels of BDNF in the striatum and the exposure to the EE prevented this effect. These results suggest that plastic brain changes induced by EE promote beneficial effects on the progression of neuronal impairment related to PD.

Variants in SNCA Gene Are Associated with Parkinson’s Disease Risk and Cognitive Symptoms in a Brazilian Sample

Genetic susceptibility contributes to the etiology of sporadic Parkinson’s Disease (PD) and worldwide studies have found positive associations of polymorphisms in the alpha-synuclein gene (SNCA) with the risk for PD. However, little is known about the influence of variants of SNCA in individual traits or phenotypical aspects of PD. Further, there is a lack of studies with Latin-American samples. We evaluated the association between SNCA single nucleotide polymorphisms (single nucleotide polymorphisms, SNPs – rs2583988, rs356219, rs2736990, and rs11931074) and PD risk in a Brazilians sample. In addition, we investigated their potential interactions with environmental factors and specific clinical outcomes (motor and cognitive impairments, depression, and anxiety). A total of 105 PD patients and 101 controls participated in the study. Single locus analysis showed that the risk allele of all SNPs were more frequent in PD patients (p < 0.05), and the associations of SNPs rs2583988, rs356219, and rs2736990 with increased PD risk were confirmed. Further, the G-rs356219 and C-rs2736990 alleles were associated with early onset PD. T-rs2583988, G-rs356219 and C-2736990 alleles were significantly more frequent in PD patients with cognitive impairments than controls in this condition. In addition, in a logistic regression model, we found an association of cognitive impairment with PD, and the practice of cognitive activity and smoking habits had a protective effect. This study shows for the first time an association of SNCA polymorphism and PD in a South-American sample. In addition, we found an interaction between SNP rs356219 and a specific clinical outcome, i.e., the increased risk for cognitive impairment in PD patients.

Carvacrol prevents impairments in motor and neurochemical parameters in a model of progressive parkinsonism induced by reserpine

Parkinsons disease (PD) is a neurodegenerative disease characterized by a progressive degeneration of dopaminergic neurons in the substantia nigra pars compact (SNpc), with consequent depletion of dopamine in the striatum, which gives rise to the characteristic motor symptoms of PD. Although its etiology is unknown, several studies have suggested that oxidative stress plays a critical function in the pathophysiology of PD, and antioxidant agents could be helpful to slown down the dopaminergic neurodegeneration. Carvacrol (CA) is a phenolic monoterpene found in essential oils of many aromatic plants that presents antioxidant and neuroprotective effects. This study aimed to assess the effect of CA in a reserpine (RES)-induced rat model of PD. Male Wistar rats received 15 s.c. injections of 0.1 mg/kg RES or vehicle, every other day, concomitantly to daily i.p. injections of CA (12.5 or 25 mg/kg) or vehicle. Across the treatment, the animals were submitted to behavioral evaluation in the catalepsy test (performed daily), open field test (7th day) and assessment of vacuous chewing movements (12th, 20th and 30th days). Upon completion of behavioral tests, rats were perfused and their brains underwent tyrosine hydroxylase (TH) immunohistochemical analysis. Our results showed that CA (12.5 e 25 mg/kg) prevented the increase in catalepsy behavior and number of vacuous chewing movements, but failed to revert the decreased open-field locomotor activity induced by RES. In addition, CA in both doses prevented the decrease in TH immunostaining induced by RES in the SNpc and dorsal striatum. Taken together, our results suggest that CA shows a protective effect in a rat model of PD, preventing motor and neurochemical impairments induced by RES. Thus, the use of CA as a promising new strategy for the prevention and/or treatment of PD may be considered.

Non-visual exploration of novel objects increases the levels of plasticity factors in the rat primary visual cortex

Background Historically, the primary sensory areas of the cerebral cortex have been exclusively associated with the processing of a single sensory modality. Yet the presence of tactile responses in the primary visual (V1) cortex has challenged this view, leading to the notion that primary sensory areas engage in cross-modal processing, and that the associated circuitry is modifiable by such activity. To explore this notion, here we assessed whether the exploration of novel objects in the dark induces the activation of plasticity markers in the V1 cortex of rats. Methods Adult rats were allowed to freely explore for 20 min a completely dark box with four novel objects of different shapes and textures. Animals were euthanized either 1 (n = 5) or 3 h (n = 5) after exploration. A control group (n = 5) was placed for 20 min in the same environment, but without the objects. Frontal sections of the brains were submitted to immunohistochemistry to measure protein levels of egr-1 and c-fos, and phosphorylated calcium-dependent kinase (pCaKMII) in V1 cortex. Results The amount of neurons labeled with monoclonal antibodies against c-fos, egr-1 or pCaKMII increased significantly in V1 cortex after one hour of exploration in the dark. Three hours after exploration, the number of labeled neurons decreased to basal levels. Conclusions Our results suggest that non-visual exploration induces the activation of immediate-early genes in V1 cortex, which is suggestive of cross-modal processing in this area. Besides, the increase in the number of neurons labeled with pCaKMII may signal a condition promoting synaptic plasticity.

Deltamethrin Intranasal administration induces memory, emotional and tyrosine hydroxylase immunoreactivity alterations in rats

Parkinsons disease (PD) is a neurodegenerative disease related to the dopaminergic system. The etiology is not fully understood, but it is known that PD is a multifactorial disease that involves genetic and environmental factors, including pesticides. One of these, Deltamethrin (DM), has been widely used for vector control in crops, farming, veterinary medicine and domestic pest control. The purpose of the present study was to investigate the effect of DM repeated administration on motor, cognitive and emotional behavior and dopaminergic parameters. Male Wistar rats received 3 intranasal (i.n.) injections of 100 μL (50 μL/nostril) of DM 0.5 μg/μl or Vehicle (saline solution 0.9%), one injection per week. We observed that DM caused memory (novel object recognition task) and emotion (contextual conditioned fear) alterations accompanied by reduction of TH immunoreactivity in the substantia nigra pars compacta (SNpc) and ventral tegmental area (VTA), and increase of TH immunoreactivity in the dorsal striatum. Motor alterations (catalepsy and open field task) were not observed throughout treatment. These findings suggest a possible early disruption of the dopaminergic pathway caused by repeated DM exposure, similar to that observed in early stages of PD.

Proposta de monitoramento dos impactos do ecoturismo no Parque Nacional Serra de Itabaiana, Sergipe

O Parque Nacional Serra de Itabaiana (PARNASI), apesar de sua importância para a conservacao da sua biodiversidade e do seu potencial para a pratica do ecoturismo, da educacao ambiental e de pesquisa cientifica, e uma unidade de conservacao de protecao integral com entraves para a sua implementacao. Visando subsidiar a elaboracao do Plano de Manejo do PARNASI, esta pesquisa objetivou caracterizar os impactos ambientais, determinar os criterios do uso da trilha da Via Sacra, da trilha do Salao dos Negros, da trilha do Veu de Noivas e da trilha do Caldeirao localizadas no interior do PARNASI. Foram identificados impactos ambientais como lixo; alargamento das trilhas, clareiras, trilhas secundarias, fogueiras, arvores danificadas, animais domesticos, poluicao sonora. Conclui-se que o parque encontra-se sem ferramentas eficientes de gestao, tais como planejamento e monitoramento das trilhas, infra-estrutura de minimo impacto, programas de educacao e interpretacao ambiental, fiscalizacao, desapropriacao das terras que estao no interior do parque; recursos humanos suficientes e capacitados. Para que os impactos negativos sejam minimizados e preciso implementar politicas publicas de cunho socioambiental que considere o ecoturismo como instrumento para o desenvolvimento sustentavel da regiao, uma vez que, concomitante com a geracao de emprego e renda para a comunidade local, conserva o meio ambiente.