Involvement of anti-inflammatory, antioxidant, and BDNF up-regulating properties in the antipsychotic-like effect of the essential oil of Alpinia zerumbet in mice: a comparative study with olanzapine.

The current drug therapy for schizophrenia effectively treats acute psychosis and its recurrence; however, this mental disorder's cognitive and negative symptoms are still poorly controlled. Antipsychotics present important side effects, such as weight gain and extrapyramidal effects. The essential oil of Alpinia zerumbet (EOAZ) leaves presents potential antipsychotic properties that need further preclinical investigation. Here, we determined EAOZ effects in preventing and reversing schizophrenia-like symptoms (positive, negative, and cognitive) induced by ketamine (KET) repeated administration in mice and putative neurobiological mechanisms related to this effect. We conducted the behavioral evaluations of prepulse inhibition of the startle reflex (PPI), social interaction, and working memory (Y-maze task), and verified antioxidant (GSH, nitrite levels), anti-inflammatory [interleukin (IL)-6], and neurotrophic [brain-derived neurotrophic factor (BDNF)] effects of this oil in hippocampal tissue. The atypical antipsychotic olanzapine (OLZ) was used as standard drug therapy. EOAZ, similarly to OLZ, prevented and reversed most KET-induced schizophrenia-like behavioral alterations, i.e., sensorimotor gating deficits and social impairment. EOAZ had a modest effect on the prevention of KET-associated working memory deficit. Compared to OLZ, EOAZ showed a more favorable side effects profile, inducing less cataleptic and weight gain changes. EOAZ efficiently protected the hippocampus against KET-induced oxidative imbalance, IL-6 increments, and BDNF impairment. In conclusion, our data add more mechanistic evidence for the anti-schizophrenia effects of EOAZ, based on its antioxidant, anti-inflammatory, and BDNF up-regulating actions. The absence of significant side effects observed in current antipsychotic drug therapy seems to be an essential benefit of the oil.

Efeitos da técnica isostretching em pacientes com escoliose: uma revisão sistemática / Isostretching technique effects in patients with scoliosis: systematic review

Introdução: O isostreching é uma modalidade terapêutica onde o tratamento é focado na melhora dos desequilíbrios posturais. Objetivo: Identificar os efeitos da técnica isostreching no tratamento da escoliose. Métodos: Trata-se de uma revisão sistemática de estudos publicados entre os anos de 1997 e 2017. Foram utilizados os termos de busca: escoliose, isostretching, isolados e associados em português e em inglês nas bases de dados Google acadêmico, SciELO; PEDro; PubMed; Bireme e Cochrane. Resultados: Durante a pesquisa foram encontrados 314 artigos, após a leitura e os critérios estabelecidos, foram selecionados para compor a revisão 6 estudos. A técnica apresentou resultados positivos em relação ao padrão postural, gibosidade e ângulo de Cobb. Conclusão: Pode-se concluir que a técnica de isostretching na escoliose teve resultados positivos, entretanto os resultados ainda são bastante discutíveis, haja visto que a quantidade de ensaios clínicos que abordaram o tema é baixa.

Introduction: Isostreching is a therapeutic modality where treatment is focused on the improvement of postural imbalances. Objective: To identify the effects of the isostreching technique in the treatment of scoliosis. Methods: This is a systematic review of studies published between 1997 and 2017. The search terms were: scoliosis, isostretching, isolated and associated in Portuguese and English in the databases Google academic, SciELO; Pedro; PubMed; Bireme and Cochrane. Results: During the research, 314 articles were found, after reading and the established criteria, 6 studies were selected to compose the review. The technique presented positive results in relation to the postural pattern, gibosity and Cobb angle. Conclusion: In this way, the technique of isostretching in scoliosis had positive results, however the results are still quite controversial, since the number of clinical trials that approached the subject is very low.

Evidence for protective effect of lipoic acid and desvenlafaxine on oxidative stress in a model depression in mice.

Oxidative stress is implicated in the neurobiology of depression. Here we investigated oxidative alterations in brain areas of animals submitted to the model of depression induced by corticosterone (CORT) and the effects of the antioxidant compound alpha-lipoic acid (ALA) alone or associated with the antidepressant desvenlafaxine (DVS) in these alterations. Female mice received vehicle or CORT (20 mg/kg) during 14 days. From the 15th to 21st days different animals received further administrations of: vehicle, DVS (10 or 20 mg/kg), ALA (100 or 200 mg/kg), or the combinations of DVS10+ALA100, DVS20+ALA100, DVS10+ALA200, or DVS20+ALA200. Twenty-four hours after the last drug administration prefrontal cortex (PFC), hippocampus (HC) and striatum (ST) were dissected for the determination of the activity of superoxide dismutase (SOD), reduced glutathione (GSH) and lipid peroxidation (LP) levels. CORT significantly increased SOD activity in the PFC and HC, decreased GSH levels in the HC and increased LP in all brain areas studied when compared to saline-treated animals. Decrements of SOD activity were observed in all groups and brain areas studied when compared to controls and CORT. The hippocampal decrease in GSH was reversed by ALA100, DVS10+ALA100, DVS20+ALA100 and DVS20+ALA200. The same DVS+ALA combination groups presented increased levels of GSH in the PFC and ST. The greater GSH levels were observed in the PFC, HC and ST of DVS20+ALA200 mice. LP was reversed in the groups ALA200 (PFC), DVS10+ALA100, DVS20+ALA100 (PFC, HC and ST), and DVS20+ALA200 (PFC, HC). Our findings contribute to the previous preclinical evidences implicating ALA as a promising agent for augmentation therapy in depression.

Evidences for a progressive microglial activation and increase in iNOS expression in rats submitted to a neurodevelopmental model of schizophrenia: reversal by clozapine.

Schizophrenia was proposed as a progressive neurodevelopmental disorder. In this regard herein we attempted to determine progressive inflammatory and oxidative alterations induced by a neonatal immune challenge and its possible reversal by clozapine administration. For this end, Wistar rats at postnatal day (PN) 5-7 were administered the viral mimetic polyriboinosinic-polyribocytidilic acid (polyI:C) or saline. A distinct group of animals additionally received the antipsychotic drug clozapine (25mg/kg) from PN60 to 74. At PN35 (periadolescence), 60 (adult) and 74 (adulthood) the animals were submitted to behavioral determinations of prepulse inhibition of the startle (PPI) and Y maze task for working memory evaluation. At PN35 and 74 the animals were sacrificed and the hippocampus (HC), prefrontal cortex (PFC) and striatum (ST) immunostained for Iba-1, a microglial marker, and inducible nitric oxide synthase (iNOS). At PN74 oxidative stress parameters, such as, reduced glutathione levels (GSH) and lipid peroxidation were determined. The results showed a progressive increase of microglial activation and iNOS immunostaining from PN35 to PN74 mainly in the CA2 and CA3 regions of the HC and in the ST. At PN74 neonatal challenge also induced an oxidative imbalance. These inflammatory alterations were accompanied by deficits in PPI and working memory only in adult life that were reversed by clozapine. Clozapine administration reversed microglial activation and iNOS increase, but not the alterations of oxidative stress parameters. Taken together these results give further evidences for a neuroprogressive etiology and course of schizophrenia and that clozapine may partly alleviate this process.

Prevention of haloperidol-induced alterations in brain acetylcholinesterase activity by vitamins B co-administration in a rodent model of tardive dyskinesia.

Tardive dyskinesia (TD) is an iatrogenic syndrome being a significant adverse outcome of typical and atypical antipsychotic therapy. Recently we demonstrated that vitamins B (B1, B6, B12 alone or in combination) were able to prevent haloperidol-induced orofacial dyskinesia (OD) possibly by their antioxidant activity in the striatum, using a well-established model of TD. Here, based on the fact that alterations in cholinergic neurotransmission are related to TD pathophysiology and that vitamins B seems to influence brain cholinergic neurotransmission, we decided to investigate the effects of vitamins B1, B6, B12 and their association, vitamin B cocktail in haloperidol-induced cholinergic alterations, evaluated by alterations in acetylcholinesterase (AChE) activity, in striatum, prefrontal cortex and hippocampus, as a way to determine the participation of cholinergic neurotransmission, in these vitamins antidyskinetic mechanism. Haloperidol 1 mg/kg i.p. daily administration during 21 days to Wistar rats caused OD while decreased AChE activity in all brain areas studied. Vitamins B administration (B1:B6:B12 at 60:60:0.6 mg/kg, s.c) alone and vitamin B cocktail co-administered with haloperidol prevented OD development and increased AChE activity in all brain areas studied, with the maximum activity increment observed in the hippocampus of the animals co-treated with vitamin B12 and vitamin B cocktail. The antidyskinetic drug, clozapine did not induce OD and increased AChE activity similarly to the groups coadministered with vitamin B and HAL. The present data suggest that vitamins B can prevent haloperidol-induced alterations in AChE activity what can be related to the mechanism underlying their antidyskinetic effect.

B vitamins attenuate haloperidol-induced orofacial dyskinesia in rats: possible involvement of antioxidant mechanisms.

Tardive dyskinesia (TD) is a serious motor disorder related to antipsychotic therapy, whose pathophysiology is associated to oxidative stress. Treatments that maintain antipsychotic efficacy while reducing TD risk are awaited. Haloperidol (HAL), a typical antipsychotic, is used as a putative murine model of TD. Here, we evaluated the protective role of vitamins B1, B6, and B12 alone or in combination (vitamin B cocktail) in preventing the HAL-induced orofacial dyskinesia (OD), based on their antioxidant properties. HAL (1 mg/kg) administered intraperitoneally to Wistar rats for 21 days caused OD and increased catalepsy time. The daily administration of B vitamins (B1 : B6 : B12 at 60 : 60 : 0.6 mg/kg) alone or the vitamin B cocktail, along with HAL, prevented the development of OD. Catalepsy time reduced in all groups treated with B vitamins, but to a lesser extent than OD. The participation of oxidative stress was assessed by the determination of reduced glutathione (GSH) levels and lipid peroxide formation in the striatum. HAL significantly decreased GSH levels and enhanced lipid peroxidation, whereas B1, B12, and vitamin B cocktail prevented the decrease in GSH levels. All groups treated with B vitamins presented a decrease in lipid peroxide formation. The data suggest a promising role for B vitamins in the prevention of OD.

Inhibition of ketamine-induced hyperlocomotion in mice by the essential oil of Alpinia zerumbet: possible involvement of an antioxidant effect.

OBJECTIVES: The antipsychotic, hypnotic, myorelaxant and antioxidant effects of the essential oil of Alpinia zerumbet (EOAZ) were studied. METHODS: EOAZ (50, 100 and 200 mg/kg i.p.) was administered once to mice for the determination of antipsychotic activity (evaluated by ketamine-induced hyperlocomotion), hypnotic activity (induced by sodium pentobarbital, 40 mg/kg i.p.), motor coordination (rotarod test), antioxidant effects (determination of lipid peroxidation and GSH levels), as well as alterations in nitric oxide levels (determination of nitrite content). KEY FINDINGS: EOAZ at doses of 100 and 200 mg/kg prevented ketamine hyperlocomotion, as did haloperidol (0.2 mg/kg i.p). EOAZ at a dose of 200 mg/kg decreased sleep latency, while all doses increased sleeping time. There was no effect on motor coordination. The in-vitro antioxidant capacity of the oil caused a decrease in lipid peroxidation and increase in GSH levels. EOAZ also prevented the decrease in nitrite content caused by oxidative stress. CONCLUSIONS: The results suggest antipsychotic and antioxidant effects for the EOAZ that may have promising efficacy for the treatment of schizophrenia.