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Introduction: Congenital Muscular Dystrophy type 1D (MDC1D) is characterized by a hypoglycosylation of α-dystroglycan protein (α-DG), and this may be strongly implicated in increased skeletal muscle tissue degeneration and abnormal brain development, leading to cognitive impairment. However, the pathophysiology of brain involvement is still unclear. Low-intensity exercise training (LIET) is known to contribute to decreased muscle degeneration in animal models of other forms of progressive muscular dystrophies., Aim: The objective of this study was to analyze the effects of LIET on cognitive involvement and oxidative stress in brain tissue and gastrocnemius muscle., Methods: Male homozygous (Large myd-/- ), heterozygous (Large myd+/- ), and wild-type mice were used. To complete 28 days of life, they were subjected to a low-intensity exercise training (LIET) for 8 weeks. After the last day of training, 24 h were expected when the animals were submitted to inhibitory avoidance and open-field test. The striatum, prefrontal cortex, hippocampus, cortex, and gastrocnemius were collected for evaluation of protein carbonylation, lipid peroxidation, and catalase and superoxide dismutase activity., Results: LIET was observed to reverse the alteration in aversive and habituation memory. Increased protein carbonylation in the striatum, prefrontal cortex, and hippocampus and lipid peroxidation in the prefrontal cortex and hippocampus were also reversed by LIET. In the evaluation of the antioxidant activity, LIET increased catalase activity in the hippocampus and cortex. In the gastrocnemius, LIET decreased the protein carbonylation and lipid peroxidation and increased catalase and superoxide dismutase activity., Conclusion: In conclusion, it can be inferred that LIET for 8 weeks was able to reverse the cognitive damage and oxidative stress in brain tissue and gastrocnemius muscle in MDC1D animals., (© 2022. Fondazione Società Italiana di Neurologia.)

Microglia are involved in many dynamic processes in the central nervous system (CNS) including the development of inflammatory processes and neuromodulation. Several sedative, analgesic or anaesthetic drugs, such as opioids, ∝ 2 -adrenergic agonists, ketamine, benzodiazepines and propofol can cause both neuroprotective and harmful effects on the brain. The purpose of this review is to present the main findings on the use of these drugs and the mechanisms involved in microglial activation. Alpha 2-adrenergic agonists, propofol and benzodiazepines have several pro- or anti-inflammatory effects on microglia. Long-term use of benzodiazepines and propofol causes neuroapoptotic effects and α 2 -adrenergic agonists may attenuate these effects. Conversely, morphine and fentanyl may have proinflammatory effects, causing behavioural changes in patients and changes in cell viability in vitro. Conversely, chronic administration of morphine induces CCL5 chemokine expression in microglial cells that promotes their survival., (Copyright © 2021. Published by Elsevier Ltd.)

Sepsis is an organ dysfunction caused by a host's unregulated response to infection, causing long-term brain dysfunction with microglial activation, the release of inflammatory components, and mitochondrial changes. Neuroinflammation can increase the expression of the 18-kD translocator protein (TSPO) in the mitochondria, leading to the activation of the microglia and the release of inflammatory components. The antagonist PK-11195 can modulate TSPO and reduce microglial activation and cognitive damage presented in an animal model of sepsis. The aim of this was to evaluate the effects of PK-11195 on long-term brain inflammation and cognitive impairment in an animal model of sepsis. Wistar rats, 60 days old, were submitted to cecal ligation and puncture (CLP) surgery, divided into groups control/saline, control/PK-11195, sepsis/saline, and sepsis/PK-11195. Immediately after surgery, the antagonist PK-11195 was administered at a dose of 3 mg/kg. Ten days after CLP surgery, the animals were submitted to behavioral tests and determination of brain inflammatory parameters. The sepsis/saline group presented cognitive damage. However, there was damage prevention in animals that received PK-11195. Besides, the sepsis increased the levels of cytokines and M1 microglia markers and caused oxidative damage. However, PK-11195 had the potential to decrease inflammation. These events show that the modulation of neuroinflammation during sepsis by PK-11195, possibly related to changes in TSPO, improves mitochondrial function in the animals' brains. In conclusion, the antagonist PK-11195 attenuated brain inflammation and prevented cognitive impairment in animals subjected to sepsis.

The present study aimed to evaluate the effect of folic acid treatment in an animal model of aging induced by D-galactose (D-gal). For this propose, adult male Wistar rats received D-gal intraperitoneally (100 mg/kg) and/or folic acid orally (5 mg/kg, 10 mg/kg or 50 mg/kg) for 8 weeks. D-gal caused habituation memory impairment, and folic acid (10 mg/kg and 50 mg/kg) reversed this effect. However, folic acid 50 mg/kg per se caused habituation memory impairment. D-gal increased the lipid peroxidation and oxidative damage to proteins in the prefrontal cortex and hippocampus from rats. Folic acid (5 mg/kg, 10 mg/kg, or 50 mg/kg) partially reversed the oxidative damage to lipids in the hippocampus, but not in the prefrontal cortex, and reversed protein oxidative damage in the prefrontal cortex and hippocampus. D-gal induced synaptophysin and BCL-2 decrease in the hippocampus and phosphorylated tau increase in the prefrontal cortex. Folic acid was able to reverse these D-gal-related alterations in the protein content. The present study shows folic acid supplementation as an alternative during the aging to prevent cognitive impairment and brain alterations that can cause neurodegenerative diseases. However, additional studies are necessary to elucidate the effect of folic acid in aging.

Ammonia is involved in the pathogenesis of neurological conditions associated with hyperammonemia, including hepatic encephalopathy. Few is known about the effects of gestational exposition to ammonia in the developing brain, and the possible long-term consequences of such exposure. We aimed to evaluate the effects of ammonia exposure during the gestation and the possible long-term cognitive alterations on pups. Eight female rats were divided into two groups: (1) control (saline solution); (2) ammonia (ammonium acetate, 2,5mmol/Kg). Each rat received a single subcutaneous injection during all gestational period. The brains from 1-day-old rats were obtained to the determination of thiobarbituric acid reactive species (TBARS), protein carbonyl and nitrite/nitrate levels. Some animals were followed 30 days after delivery and were subjected to the step-down inhibitory avoidance task. It was observed a significant increase in protein carbonyl, but not TBARS or nitrite/nitrate levels, in pups exposed to ammonia. Rats exposed to ammonia presented long-term cognitive impairment. Gestational exposition to ammonia induces protein oxidative damage in the neonatal rat brain, and long-term cognitive impairment.

Sepsis is caused by a dysregulated host response to infection, often associated with acute central nervous system (CNS) dysfunction, which results in long-term cognitive impairment. Dimethyl fumarate (DMF) is an important agent against inflammatory response and reactive species in CNS disorders. Evaluate the effect of DMF on acute and long-term brain dysfunction after experimental sepsis in rats. Male Wistar rats were submitted to the cecal ligation and puncture (CLP) model. The groups were divided into sham (control) + vehicle, sham + NAC, sham + DMF, CLP + vehicle, CLP + NAC, and CLP + DMF. The animals were treated with DMF (15 mg/kg at 0 and 12 h after CLP, per gavage) and the administration of n-acetylcysteine (NAC) (20 mg/kg; 3, 6, and 12 h after CLP, subcutaneously) was used as positive control. Twenty-four hours after CLP, cytokines, myeloperoxidase (MPO), nitrite/nitrate (N/N), oxidative damage to lipids and proteins, and antioxidant enzymes were evaluated in the hippocampus, total cortex, and prefrontal cortex. At 10 days after sepsis induction, behavioral tests were performed to assess cognitive damage. We observed an increase in cytokine levels, MPO activity, N/N concentration, and oxidative damage, a reduction in SOD and GPx activity in the brain structures, and cognitive damage in CLP rats. DMF treatment was effective in reversing these parameters. DMF reduces sepsis-induced neuroinflammation, oxidative stress, and cognitive impairment in rats subjected to the CLP model.

The present study aims to investigate the oxidative stress parameters in isolated mitochondria, as well as looking at mitochondrial complex activity in patients with Bipolar Disorder (BD) during depressive or euthymic episodes. This study evaluated the levels of mitochondrial complex (I, II, II-III and IV) activity in lymphocytes from BD patients. We evaluated the following oxidative stress parameters: superoxide, thiobarbituric acid reactive species (TBARS) and carbonyl levels in submitochondrial particles of lymphocytes from bipolar patients. 51 bipolar patients were recruited into this study: 34 in the euthymic phase, and 17 in the depressive phase. Our results indicated that the depressive phase could increase the levels of mitochondrial superoxide, carbonyl and TBARS, and superoxide dismutase, and could decrease the levels of mitochondrial complex II activity in the lymphocytes of bipolar patients. It was also observed that there was a negative correlation between the Hamilton Depression Rating Scale (HDRS) and complex II activity in the lymphocytes of depressive bipolar patients. In addition, there was a positive correlation between HDRS and superoxide, superoxide dismutase, TBARS and carbonyl. Additionally, there was a negative correlation between complex II activity and oxidative stress parameters. In conclusion, our results suggest that mitochondrial oxidative stress and mitochondrial complex II dysfunction play important roles in the depressive phase of BD., (Copyright © 2018. Published by Elsevier B.V.)

Patients recovering from sepsis have higher rates of CNS morbidities associated with long-lasting impairment of cognitive functions, including neurodegenerative diseases. However, the molecular etiology of these sepsis-induced impairments is unclear. Here, we investigated the role of the receptor for advanced glycation end products (RAGE) in neuroinflammation, neurodegeneration-associated changes, and cognitive dysfunction arising after sepsis recovery. Adult Wistar rats underwent cecal ligation and perforation (CLP), and serum and brain (hippocampus and prefrontal cortex) samples were obtained at days 1, 15, and 30 after the CLP. We examined these samples for systemic and brain inflammation; amyloid-β peptide (Aβ) and Ser-202-phosphorylated Tau (p-Tau Ser-202 ) levels; and RAGE, RAGE ligands, and RAGE intracellular signaling. Serum markers associated with the acute proinflammatory phase of sepsis (TNFα, IL-1β, and IL-6) rapidly increased and then progressively decreased during the 30-day period post-CLP, concomitant with a progressive increase in RAGE ligands (S100B, N ϵ-[carboxymethyl]lysine, HSP70, and HMGB1). In the brain, levels of RAGE and Toll-like receptor 4, glial fibrillary acidic protein and neuronal nitric-oxide synthase, and Aβ and p-Tau Ser-202 also increased during that time. Of note, intracerebral injection of RAGE antibody into the hippocampus at days 15, 17, and 19 post-CLP reduced Aβ and p-Tau Ser-202 accumulation, Akt/mechanistic target of rapamycin signaling, levels of ionized calcium-binding adapter molecule 1 and glial fibrillary acidic protein, and behavioral deficits associated with cognitive decline. These results indicate that brain RAGE is an essential factor in the pathogenesis of neurological disorders following acute systemic inflammation., (© 2018 by The American Society for Biochemistry and Molecular Biology, Inc.)

The present study was created to investigate the effects of chronic mild stress (CMS) on the depressive behavior and neurochemical parameters of rats that were subjected to sepsis. Wistar rats were subjected to a CMS protocol, and sepsis was induced by cecal ligation and perforation (CLP). The animals were then divided into 4 separate groups; Control + Sham (n = 20), Control + CLP (n = 30), CMS + Sham (n = 20) and CMS + CLP (n = 30). Body weight, food and water intake and mortality were measured on a daily basis for a period of 10 days after the induction of sepsis. Locomotor activity, splash and forced swimming tests were performed ten days after CLP. At the end of the test period, the animals were euthanized, and the prefrontal cortex and hippocampus were removed to determine the levels of cytokines and oxidative damage. Our results show that there was no significant interaction between CMS and CLP in relation to locomotor activity and the forced swimming test. However, we did observe a significant decrease in total grooming time in the Control + CLP and CMS + Sham groups, with the CMS + CLP group showing behavior similar to that of the control animals. This was found to be related to a decrease in the levels of brain cytokines, and not to oxidative damage parameters. Collectively, our results suggest that a previous stress caused by CMS can protect the brain against the systemic acute and severe stress elicited by sepsis., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

This study investigated the behavioral and biochemical parameters of DM1 as a risk factor in an animal model of schizophrenia (SZ). All groups: 1 Control (saline+saline); 2 Alloxan (alloxan+saline); 3 Ketamine (saline+ketamine); 4 (Alloxan+Ketamine) were fasted for a period of 18h before the subsequent induction of DM via a single intraperitoneal (i.p) injection of alloxan (150mg/kg). From the 4th to the 10th days, the animals were injected i.p with ketamine (25mg/kg) or saline, once a day, to induce a model of SZ and 30min after the last administration were subjected to behavioral testing. After, the animals were decapitated and the brain structures were removed. Ketamine induced hyperactivity and in the social interaction, ketamine, alloxan and the association of alloxan+ketamine increased the latency and decreased the number of contacts between animals. The animals from the ketamine, alloxan and alloxan+ketamine groups showed a prepulse startle reflex (PPI) deficit at the three intensities (65, 70 and 75dB). Ketamine was shown to be capable of increasing the activity of acetylcholinesterase (AChE) in the brain structures. Combination of alloxan+ketamine seems to have an exacerbated effect within the cholinergic system. For lipid peroxidation and protein carbonyls, alloxan+ketamine appear to have intensified lipid and protein damage in the three structures. Ketamine and the combination of ketamine+alloxan induced DNA damage in both frequency and damage index. This research found a relationship between DM1 and SZ., (Copyright © 2017 Elsevier B.V. All rights reserved.)

d-Galactose (d-gal) is a reducing sugar that can be used to mimic the characteristics of aging in rodents; however, the effects of d-gal administration by oral route are not clear. Therefore, the aim of this study was to elucidate if the oral administration of d-gal induces cognitive impairments, neuronal loss, and oxidative damage, mimicking an animal model of aging. Male adult Wistar rats (4 months old) received d-gal (100mg/kg) via the oral route for a period of 1, 2, 4, 6 or 8 weeks. The results showed cognitive impairments in the open-field test in the 4th and 6th weeks after d-gal administration, as well as an impairment in spatial memory in the radial maze test after the 6th week of d-gal administration. The results indicated increase of levels of thiobarbituric acid reactive species-TBARS-and carbonyl group content in the prefrontal cortex from the 4th week, and in all weeks of d-gal administration, respectively. An increase in the levels of TBARS and carbonyl group content was observed in the hippocampus over the entire period of d-gal treatment. In the 8th week of d-gal administration, we also observed reductions in synaptophysin and TAU protein levels in the prefrontal cortex. Thus, d-gal given by oral route caused cognitive impairments which were accompanied by oxidative damage. Therefore, these results indicate that orally administered d-gal can induce the behavioral and neurochemical alterations that are observed in the natural aging process. However, oral d-gal effect in rats deserve further studies to be better described., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Background: Ketamine, an antagonist of N-methyl-d-aspartate (NMDA) receptors, has presented antidepressant effects in basic and clinical studies. The MAPK kinase (MEK) signaling pathway could be a target for novel antidepressant drugs and an important pathway involved in neuronal plasticity. Thus, this study evaluated the effects of the administration of ketamine on the phosphorylation of TrKB and CREB, and oxidative stress parameters in the prefrontal cortex (PFC), hippocampus, amygdala, and nucleus accumbens (NAc) rats, after the inhibition of MAPK pathway (PD184161)., Methods: Male adult Wistar rats were submitted to a surgical procedure to receive a single dose of a pharmacological inhibitor of MAPK (PD184161) at a dose of (0.1μg/μl) or vehicle. Then, they were divided: 1) vehicle+saline; 2) inhibitor PD184161+saline; 3) vehicle+ketamine 15mg/kg; and 4) inhibitor PD184161+ketamine 15mg/kg., Results: MEK inhibitor and ketamine increased the phosphorylation of the transcription factor cAMP response element-binding protein (pCREB) and neurotrophic factor/tropomyosin related kinase B receptor (pTrKB) in the PFC, and decreased pCREB in the hippocampus. The MEK inhibitor abolished ketamine's effects in the hippocampus. In the amygdala, pCREB was decreased, and pTrKB was increased after MEK inhibitor plus ketamine. Ketamine increased the thiobarbituric acid reactive species (TBARS) in the PFC, hippocampus, amygdala, and NAc; MEK inhibitor antagonized these effects. The carbonyl was increased in the PFC by both ketamine and MEK inhibitor, but inhibitor infusion plus ketamine administration reduced this effect. In the amygdala, MEK inhibitor increased carbonyl., Conclusion: Ketamine's effects on pCREB, pTrKB, and oxidative stress are mediated, at least in part, by a mechanism dependent of MAPK signaling inhibition., (Copyright © 2015 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.)

Studies have consistently reported the participation of oxidative stress in bipolar disorder (BD). Evidence indicates that epigenetic regulations have been implicated in the pathophysiology of mood disorders. Considering these evidences, the present study aimed to investigate the effects of sodium butyrate (SB), a histone deacetylase (HDAC)inhibitor, on manic-like behavior and oxidative stress parameters (TBARS and protein carbonyl content and SOD and CAT activities) in frontal cortex and hippocampus of rats subjected to the animal model of mania induced by intracerebroventricular (ICV) ouabain administration.The results showed that SB reversed ouabain-induced hyperactivity, which represents a manic-like behavior in rats. In addition, the ouabain ICV administration induced oxidative damage to lipid and protein and alters antioxidant enzymes activity in all brain structures analyzed. The treatment with SB was able to reversesboth behavioral and oxidative stress parameters alteration induced by ouabain.In conclusion, we suggest that SB can be considered a potential new mood stabilizer by acts on manic-like behavior and regulatesthe antioxidant enzyme activities, protecting the brain against oxidative damage., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Several mechanisms are associated with brain dysfunction during sepsis; one of the most important are activation of microglia and astrocytes. Activation of glial cells induces changes in permeability of the blood-brain barrier, secretion of inflammatory cytokines, and these alterations could induce neuronal dysfunction. Furthermore, blood-borne leukocytes can also reach the brain and participate in inflammatory response. Mechanisms involved in sepsis-associated brain dysfunction were revised here, focusing in neuroinflammation and involvement of blood-borne leukocytes and glial cells in this process.

New studies suggest that polyunsaturated fatty acids, such as omega-3, may reduce the symptoms of schizophrenia. The present study evaluated the preventive effect of omega-3 on interleukines (IL) and neurotrophin brain-derived neurotrophic factor (BDNF) levels in the brains of young rats subjected to a model of schizophrenia. Treatment was performed over 21 days, starting on the 30th day of rat's life. After 14 days of treatment with omega-3 or vehicle, a concomitant treatment with saline or ketamine (25 mg/kg) was started and maintained until the last day of the experiment. BDNF levels in the rat's prefrontal cortex were decreased at 1 h and 24 h after the last administration of ketamine, whereas the group administered with ketamine and omega-3 showed a decrease in BDNF levels only after 24 h. In contrast, both interventions induced similar responses in levels of IL-1β and IL6. These findings suggest that the similarity of IL-1β and IL6 levels in our experimental groups is due to the mechanism of action of ketamine on the immune system. More studies have to be carried out to explain this pathology. In conclusion, according to previous studies and considering the current study, we could suggest a prophylactic role of omega-3 against the outcome of symptoms associated with schizophrenia.

Several studies have suggested that alterations in brain-derived neurotrophic factor (BDNF) and increased oxidative stress have a central role in bipolar disorder (BD). Intracerebroventricular (ICV) injection of ouabain (OUA) in rats alters oxidative stress parameters and decreases BDNF levels in the brain. In this context, the present study aims to investigate the effects of BDNF ICV administration on BDNF levels and oxidative stress parameters in brains of rats submitted to animal model of mania induced by OUA. Wistar rats received an ICV injection of OUA, artificial cerebrospinal fluid (ACSF), OUA plus BDNF, or ACSF plus BDNF. Locomotor activity and risk-taking behavior in the rats were measured using the open-field test. In addition, we analyzed the BDNF levels and oxidative stress parameters (TBARS, Carbonyl, CAT, SOD, GR, and GPx) in the frontal cortex and hippocampus of rats. The BDNF was unable to reverse the ouabain-induced hyperactivity and risk-taking behavior. Nevertheless, BDNF treatment increased BDNF levels, modulated the antioxidant enzymes, and protected the OUA-induced oxidative damage in the brain of rats. These results suggest that BDNF alteration observed in BD patients may be associated with oxidative damage, both seen in this disorder.

Bipolar disorder (BD) is a severe psychiatric disorder associated with social and functional impairment. Some studies have strongly suggested the involvement of oxidative stress in the pathophysiology of BD. Paradoxal sleep deprivation (PSD) in mice has been considered a good animal model of mania because it induces similar manic-like behavior, as well as producing the neurochemical alterations which have been observed in bipolar patients. Thus, the objective of the present study was to evaluate the effects of the antioxidant agent's n-acetylcysteine (Nac) and/or deferoxamine (DFX) on behavior and the oxidative stress parameters in the brains of mice submitted to the animal model of mania induced by PSD. The mice were treated for a period of seven days with saline solution (SAL), Nac, DFX or Nac plus DFX. The animals were subject to the PSD protocol for 36 h. Locomotor activity was then evaluated using the open-field test, and the oxidative stress parameters were subsequently evaluated in the hippocampus and frontal cortex of mice. The results showed PSD induced hyperactivity in mice, which is considered a manic-like behavior. In addition to this, PSD increased lipid peroxidation and oxidative damage to proteins, as well as causing alterations to antioxidant enzymes in the frontal cortex and hippocampus of mice. The Nac plus DFX adjunctive treatment prevented both the manic-like behavior and oxidative damage induced by PSD. Improving our understanding relating to oxidative damage in biomolecules, and the antioxidant mechanisms presented in the animal models of mania are important in helping to improve our knowledge concerning the pathophysiology and development of new therapeutical treatments for BD., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Epigenetic mechanisms are involved in normal behavior and are implicated in several brain neurodegenerative conditions, psychiatric and inflammatory diseases as well. Moreover, it has been demonstrated that sepsis lead to an imbalance in acetylation of histones and that histone deacetylase inhibitors (HDACi) can reverse this condition. In the present study, we evaluated the effects of a microinjection of sodium butyrate (SB, HDACi) into cerebral ventricle on aversive memory in rats submitted to the sepsis. Rats were given a single intraventricular injection of artificial cerebrospinal fluid (ACSF) or SB and immediately after the stereotaxic surgery and the drug infusion, the animals were subjected to cecal ligation and perforation (CLP). The animals were killed twenty four hours or ten days after sepsis induction and the prefrontal cortex, hippocampus, striatum and cortex were obtained to the determination of histone deacetylase activity. In a separate cohort of animals 10 days after sepsis induction, it was performed the inhibitory avoidance task. SB administration was able to reverse the impairment in aversive memory and inhibited the HDAC activity in prefrontal cortex and hippocampus 10 days after CLP. These support a role for an epigenetic mechanism in the long-term cognitive impairments observed in sepsis survivors animals., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Streptococcus pneumoniae is a common cause of bacterial meningitis, with a high mortality rate and neurological sequelae. In contrast, folic acid plays an important role in neuroplasticity and the preservation of neuronal integrity. In the present study, we evaluated the influence of folic acid on memory, oxidative damage, enzymatic defence, and brain-derived neurotrophic factor (BDNF) expression in experimental pneumococcal meningitis. In animals that received folic acid at a dose of 10 or 50 mg, there was a reduction in both crossing and rearing during an open-field task compared with the training session, demonstrating habituation memory. During a step-down inhibitory avoidance task, there was a difference between the training and the test sessions, demonstrating aversive memory. In the hippocampus, BDNF expression decreased in the meningitis group; however, adjuvant treatment with 10 mg of folic acid increased BDNF expression, decreased lipid peroxidation, protein carbonylation, nitrate/nitrite levels, and myeloperoxidase activity and increased superoxide dismutase activity. In frontal cortex adjuvant treatment with 10 mg of folic acid decreased lipid peroxidation and protein carbonylation. There is substantial interest in the role of folic acid and related pathways in nervous system function and in folic acid's potential therapeutic effects. Here, adjuvant treatment with vitamin B9 prevented memory impairment in experimental pneumococcal meningitis.

Studies have been suggested that minocycline can be a potential new agent for the treatment of depression. In addition, both oxidative stress and energy metabolism present an important role in pathophysiology of depression. So, the present study was aimed to evaluate the effects of minocycline on stress oxidative parameters and energy metabolism in the brain of adult rats submitted to the chronic mild stress protocol (CMS). After CMS Wistar, both stressed animals as controls received twice ICV injection of minocycline (160 μg) or vehicle. The oxidative stress and energy metabolism parameters were assessed in the prefrontal cortex (PF), hippocampus (HIP), amygdala (AMY) and nucleus accumbens (Nac). Our findings showed that stress induced an increase on protein carbonyl in the PF, AMY and NAc, and mynocicline injection reversed this alteration. The TBARS was increased by stress in the PF, HIP and NAc, however, minocycline reversed the alteration in the PF and HIP. The Complex I was incrased in AMY by stress, and minocycline reversed this effect, however reduced Complex I activity in the NAc; Complex II reduced in PF and AMY by stress or minocycline; the Complex II-III increased in the HIP in stress plus minocycline treatment and in the NAc with minocycline; in the PF and HIP there were a reduced in Complex IV with stress and minocycline. The creatine kinase was reduced in AMY and NAc with stress and minocycline. In conclusion, minocycline presented neuroprotector effects by reducing oxidative damage and regulating energy metabolism in specific brain areas.

Studies have suggested that ketamine, a nonselective NMDA receptor antagonist, could be a new drug in the treatment of major depression, but the way ketamine presents such effects remains to be elucidated. Therefore, the objective of this paper was to evaluate the effects of ketamine treatment on parameters related to depression in the brain of adult rats subjected to an animal model of depression. The animals were divided into: non-deprived + saline; non-deprived + ketamine; deprived + saline; deprived + ketamine. Treatments involving ketamine (15 mg/kg) were administered once a day during 14 days in the animal's adult phase. After treatment, the brain derived-neurotrophic factor (BDNF) levels, oxidative stress and energy metabolism activity were evaluated in brain structures of rats involved in the circuit of depression. In the amygdala, hippocampus and nucleus accumbens (NAc), a reduction in BDNF levels was observed in deprived rats, but the animals treated with ketamine reversed the effects of this animal model only in the amygdala and NAc. In addition to this, the complex I activity, in deprived rats, was diminished in the prefrontal cortex (PFC) and amygdala; in the PFC and hippocampus, the complex II-III was diminished in deprived rats; still the administration of ketamine increased the complex IV activity in the PFC and amygdala of rats submitted to the maternal deprivation. In deprived rats, the creatine kinase activity was reduced in the PFC and amygdala, however the administration of ketamine reversed this decrease in the amygdala. The malondialdehyde (MDA) equivalents were increased in non-deprived rats treated with ketamine in the PFC and NAc. Carbonyl levels in the PFC were diminished in control rats that received saline. Though ketamine treatment reversed this effect in deprived rats in the PFC and hippocampus. Still, in NAc, the carbonyl levels were diminished in deprived rats. The superoxide dismutase (SOD) activity was increased in control rats that received ketamine in the PFC and NAc, and were diminished in deprived rats that received saline or ketamine in the PFC and hippocampus. These findings may help to explain that dysfunctions involving BDNF, oxidative stress and energy metabolism within specific brain areas, may be linked with the pathophysiology of depression, and antidepressant effects of ketamine can be positive, at least partially due to the control of these pathways.