Exploring Parkinson's Disease-Associated Depression: Role of Inflammation on the Noradrenergic and Serotonergic Pathways.

Parkinson's disease (PD) is a multifactorial disease, with genetic and environmental factors contributing to the disease onset. Classically, PD is a movement disorder characterized by the loss of dopaminergic neurons in the nigrostriatal pathway and intraneuronal aggregates mainly constituted of the protein α-synuclein. However, PD patients also display non-motor symptoms, including depression, which have been linked to functional abnormalities of non-dopaminergic neurons, including serotonergic and noradrenergic ones. Thus, through this comprehensive literature review, we shed light on the noradrenergic and serotonergic impairment linked to depression in PD, focusing on the putative involvement of inflammatory mechanisms.

Agmatine improves olfactory and cognitive deficits in Spontaneously Hypertensive Rats (SHR): An animal model of Attention Deficit Hyperactivity Disorder (ADHD).

Attention Deficit Hyperactivity Disorder (ADHD) is a highly prevalent and disabling disorder that frequently persists into adulthood. Many patients are considered nonresponders to typical pharmacological treatments due to insufficient symptoms' reduction or the inability to tolerate the side effects of these medications. Agmatine is an endogenous neuromodulator with emotional- and cognitive-enhancing properties that arises as a promising agent to manage several Central Nervous System disorders. Here, we investigated the effects of chronic treatment with agmatine on behavioral impairments exhibited by adult Spontaneously Hypertensive Rats (SHR), an animal model for the study of ADHD. Adult male Wistar and SHR (3-4 months old) received intraperitoneal (i.p.) treatment with saline (NaCl 0.9%) or agmatine (30 mg/kg/day) during 20 consecutive days and were evaluated in a battery of behavioral tasks. Agmatine treatment improved olfactory and recognition memory impairments of SHR evaluated in the olfactory discrimination, object recognition, and social recognition memory tasks. In addition, agmatine administration improved the cognitive flexibility in the water maze test. Agmatine did not alter SHR's locomotor activity and hedonic-like behaviors observed in the open-field and splash tests, respectively. No changes were observed in SHR's systolic blood pressure following agmatine treatment. This study provides the first evidence that agmatine improves olfactory and cognitive impairments observed in an animal model of ADHD. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Monitoramento COVID-19: Avaliação De Um Município Localizado no Estado do Paraná / COVID-19 Monitoring: Evaluation of a Municipality Located in the State of Paraná / Monitoreo COVID-19: Evaluación De Un Municipio Ubicado En el Estado de Paraná

Objetivo: descrever as ações de monitoramento e avaliar o impacto desta atividade durante a situação da pandemia. Método: trata-se de uma pesquisa epidemiológica observacional do tipo descritiva, buscando compreender o impacto, das estratégias de monitoramento no acompanhamento dos casos suspeitos e/ou confirmados pela Vigilância Epidemiológica. Resultados: houve o monitoramento de usuários com suspeita ou confirmação de síndrome gripal. Evidenciou-se a importância do monitoramento para o munícipio, pois após a busca ativa e identificação dos sintomas, possibilitou o cuidado centrado nas diretrizes assistências do SUS. Conclusão: o monitoramento se mostrou eficaz, uma vez que a maior parte dos usuários se recuperaram da infecção e tiveram seus casos acompanhados.

Objective: to describe the monitoring actions and assess the impact of this activity during the pandemic situation. Method: this is an observational epidemiological research of the descriptive type, seeking to understand the impact of the monitoring strategies in the monitoring of suspected cases and / or confirmed by the Epidemiological Surveillance. Results: there was a monitoring of users with suspected or confirmed flu syndrome. We highlighted the importance of monitoring for the municipality, because after the active search and identification of symptoms, it enabled care centered on SUS assistance guidelines. Conclusion: the monitoring proved to be effective, since most users recovered from the infection and had their cases followed up.

Objetivo: describir las acciones de monitoreo y evaluar el impacto de esta actividad durante la situación de pandemia. Metodo: se trata de una investigación epidemiológica observacional descriptiva, que busca comprender el impacto de las estrategias de monitoreo en el seguimiento de casos sospechosos y/ o confirmados por Vigilancia Epidemiológica. Resultados: se monitoreó a los usuarios con sospecha o confirmación de enfermedad similar a la gripe. Resaltamos la importancia del seguimiento para el municipio, porque luego de la búsqueda activa e identificación de síntomas, permitió una atención centrada en las pautas asistenciales del SUS. Conclusión: el seguimiento demostró ser eficaz, ya que la mayoría de los usuarios se recuperaron de la infección y se les dio seguimiento a sus casos.

Caffeine Consumption plus Physical Exercise Improves Behavioral Impairments and Stimulates Neuroplasticity in Spontaneously Hypertensive Rats (SHR): an Animal Model of Attention Deficit Hyperactivity Disorder.

Attention deficit hyperactivity disorder (ADHD) is a prevalent and disabling disorder, mainly characterized by hyperactivity, inattention, and impulsivity, but also by olfactory and memory impairments that frequently persist throughout lifetime. The pathophysiology of ADHD is complex, involving several brain regions and neural pathways including alterations in adenosine neuromodulation. The administration of caffeine (a non-selective adenosine receptor antagonist) and physical exercise have been independently pointed as effective approaches for the management of ADHD symptoms. Here, we evaluated the effects of caffeine consumption (0.3 mg/mL in drinking water) plus physical exercise in running wheels during 6 weeks-starting during either adolescence (30 days old) or adulthood (4-5 months old)-on behavioral performance (including olfactory discrimination, open field, object recognition, and water maze tests) on the brain levels of monoamines (by high-performance liquid chromatography), on proteins related to synaptic plasticity and on brain-derived neurotrophic factor signaling (by Western blot analysis) in spontaneously hypertensive rats (SHRs), a validated animal model of ADHD. SHRs displayed persistent impairments of olfactory and short-term recognition memory from adolescence to adulthood, which were accompanied by lower levels of synaptosomal-associated protein 25 (SNAP-25) in the prefrontal cortex and hippocampus. The association of caffeine plus physical exercise during adolescence or adulthood restored the olfactory discrimination ability and, in an independent manner, improved short-term recognition memory of SHRs. These benefits were not associated to alterations in locomotor activity or in the hypertensive phenotype. The association of caffeine consumption plus physical exercise during adolescence increased the levels of SNAP-25, syntaxin, and serotonin in the hippocampus and prefrontal cortex, and striatal dopamine levels in SHRs. These results provide new evidence of the potential of caffeine and physical exercise, starting at adolescence or adult life, to improve behavioral impairments and stimulate neuroplasticity in ADHD.

The Gender-Biased Effects of Intranasal MPTP Administration on Anhedonic- and Depressive-Like Behaviors in C57BL/6 Mice: the Role of Neurotrophic Factors.

Depression is a highly prevalent and debilitating non-motor symptom observed during the early stages of Parkinson's disease (PD). Although PD prevalence is higher in men, the depressive symptoms in PD are more common in women. Therefore, the aim of this study was to investigate the development of anhedonic- and depressive-like behaviors in male and female mice and the potential mechanisms related to depressive symptoms in an experimental model of PD. Young adult male and female C57BL/6 mice (3 months old) received a single intranasal (i.n.) administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and were submitted to a battery of behavioral tasks (sucrose consumption, splash test, tail suspension, forced swimming and open field tests) to assess their emotional and motor profiles. Considering the role of sexual hormones in emotional behaviors, the same protocol of i.n. MPTP administration and the splash, tail suspension, and open field tests were conducted in ovariectomized (OVX) and aged C57BL/6 female (20 months old) mice. We also investigated the immunocontent of neurotrophins (BDNF, GDNF, and VEGF) in the hippocampus and prefrontal cortex by western blot. I.n.  MPTP administration induced more pronounced anhedonic- and selective depressive-like behaviors in female adult mice, also observed in OVX and aged female mice, with the absence of motor impairments. Furthermore, MPTP induced a more pronounced depletion of neurotrophins in the prefrontal cortex and hippocampus in female than male mice. This study provides new evidence of increased susceptibility of female mice to anhedonic- and depressive-like behaviors following i.n. MPTP administration. The observed gender-related effects of MPTP on emotional parameters seem to be linked to increased depletion of neurotrophins (particularly BDNF and GDNF) in the hippocampus and prefrontal cortex of female mice.

Melatoninergic System in Parkinson's Disease: From Neuroprotection to the Management of Motor and Nonmotor Symptoms.

Melatonin is synthesized by several tissues besides the pineal gland, and beyond its regulatory effects in light-dark cycle, melatonin is a hormone with neuroprotective, anti-inflammatory, and antioxidant properties. Melatonin acts as a free-radical scavenger, reducing reactive species and improving mitochondrial homeostasis. Melatonin also regulates the expression of neurotrophins that are involved in the survival of dopaminergic neurons and reduces α-synuclein aggregation, thus protecting the dopaminergic system against damage. The unbalance of pineal melatonin synthesis can predispose the organism to inflammatory and neurodegenerative diseases such as Parkinson's disease (PD). The aim of this review is to summarize the knowledge about the potential role of the melatoninergic system in the pathogenesis and treatment of PD. The literature reviewed here indicates that PD is associated with impaired brain expression of melatonin and its receptors MT1 and MT2. Exogenous melatonin treatment presented an outstanding neuroprotective effect in animal models of PD induced by different toxins, such as 6-hydroxydopamine (6-OHDA), 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), rotenone, paraquat, and maneb. Despite the neuroprotective effects and the improvement of motor impairments, melatonin also presents the potential to improve nonmotor symptoms commonly experienced by PD patients such as sleep and anxiety disorders, depression, and memory dysfunction.

Effects of Hypericum perforatum on turning behavior in an animal model of Parkinson's disease

Parkinson's disease (PD) is an age-related neurodegenerative disorder characterized by the slow and progressive death of dopaminergic neurons in the (substantia nigra pars compact). Hypericum perforatum (H. perforatum) is a plant widely used as an antidepressant, that also presents antioxidant and anti-inflammatory properties. We evaluated the effects of H. perforatum on the turning behavior of rats submitted to a unilateral administration of 6-hydroxydopamine (6-OHDA) into the medial forebrain bundle as an animal model of PD. The animals were treated with H. perforatum (100, 200, or 400 mg/kg, v.o.) for 35 consecutive days (from the 28th day before surgery to the 7th day after). The turning behavior was evaluated at 7, 14 and 21 days after the surgery, and the turnings were counted as contralateral or ipsilateral to the lesion side. All tested doses significantly reduced the number of contralateral turns in all days of evaluation, suggesting a neuroprotective effect. However, they were not able to prevent the 6-OHDA-induced decrease of tyrosine hydroxylase expression in the lesioned striatum. We propose that H. perforatum may counteract the overexpression of dopamine receptors on the lesioned striatum as a possible mechanism for this effect. The present findings provide new evidence that H. perforatum may represent a promising therapeutic tool for PD.

A Doença de Parkinson é uma doença neurodegenerativa relacionada à idade, caracterizada pela morte lenta e progressiva de neurônios dopaminérgicos da substância negra pars compacta. O Hypericum perforatum (H. perforatum) é um fitoterápico utilizado como antidepressivo, apresentando propriedades antioxidantes, anti-inflamatórias e nootrópicas. Neste trabalho, avaliaram-se os efeitos do tratamento com H. perforatum no comportamento rotatório de ratos no modelo da doença de Parkinson induzido pela administração unilateral de 6-OHDA no feixe prosencefálico medial. Ratos Wistar machos foram tratados com H. perforatum (100, 200 ou 400 mg/kg, v.o.) por 35 dias (do 28º dia antes até o 7º dia após a lesão). As rotações ipsilaterais e contralaterais à lesão foram registradas no 7º, 14º e 21º dias após a cirurgia. As três doses de H. perforatum utilizadas reduziram o número de rotações contralaterais, indicando um possível efeito neuroprotetor da planta. Porém, o H. perforatum não impediu a redução na expressão da enzima tirosina hidroxilase no estriado lesionado, quantificada por Western blot. Propomos que o H. perforatum possa bloquear o aumento da expressão dos receptores dopaminérgicos no estriado lesionado com 6-OHDA. Entretanto, estudos adicionais são necessários para identificar o mecanismo exato pelo qual o H. perforatum reduziu o número de rotações contralaterais. Os resultados do presente estudo sugerem o H. perforatum como um potencial agente terapêutico para a doença de Parkinson.