Step-down Inhibitory Avoidance Task Research Articles

New curcumin-loaded nanocapsules as a therapeutic alternative in an amnesia model.

This study aimed to investigate the action of two different formulations of curcumin (Cur)-loaded nanocapsules (Nc) (Eudragit [EUD] and poly (ɛ-caprolactone) [PCL]) in an amnesia mice model. We also investigated the formulations' effects on scopolamine-induced (SCO) depressive- and anxiety-like comorbidities, the cholinergic system, oxidative parameters, and inflammatory markers. Male Swiss mice were randomly divided into five groups (n = 8): group I (control), group II (Cur PCL Nc 10mg/kg), group III (Cur EUD Nc 10mg/kg), group IV (free Cur 10mg/kg), and group V (SCO). Treatments with Nc or Cur (free) were performed daily or on alternate days. After 30min of treatment, the animals received the SCO and were subjected to behavioral tests 30min later (Barnes maze, open-field, object recognition, elevated plus maze, tail suspension tests, and step-down inhibitory avoidance tasks). The animals were then euthanized and tissue was removed for biochemical assays. Our results demonstrated that Cur treatment (Nc or free) protected against SCO-induced amnesia and depressive-like behavior. The ex vivo assays revealed lower acetylcholinesterase (AChE) and catalase (CAT) activity, reduced thiobarbituric species (TBARS), reactive species (RS), and non-protein thiols (NSPH) levels, and reduced interleukin-6 (IL-6) and tumor necrosis factor (TNF) expression. The treatments did not change hepatic markers in the plasma of mice. After treatments on alternate days, Cur Nc had a more significant effect than the free Cur protocol, implying that Cur may have prolonged action in Nc. This finding supports the concept that it is possible to achieve beneficial effects in nanoformulations, and treatment on alternate days differs from the free Cur protocol regarding anti-amnesic effects in mice.

Cross state-dependent memory retrieval between cannabinoid CB1 and serotonergic 5-HT1A receptor agonists in the mouse dorsal hippocampus

Understanding the neurobiological mechanisms of drug-related learning and memory formation may help the treatment of cognitive disorders. Dysfunction of the cannabinoid and serotonergic systems has been demonstrated in learning and memory disorders.The present paper investigates the phenomenon called state-dependent memory (SDM) induced by ACPA (a selective cannabinoid CB1 receptor agonist) and 8-OH-DPAT (a nonselective 5-HT1A receptor agonist) with special focus on the role of the 5-HT1A receptor in the effects of both ACPA and 8-OH-DPAT SDM and cross state-dependent memory retrieval between ACPA and 8-OH-DPAT in a step-down inhibitory avoidance task.The dorsal hippocampal CA1 regions of adult male NMRI mice were bilaterally cannulated, and all drugs were microinjected into the intended injection sites. A single-trial step-down inhibitory avoidance task was used to assess memory retrieval and state-dependence.Post-training and/or pre-test microinjections of ACPA (1 and 2 ng/mouse) and 8-OH-DPAT (0.5 and 1 μg/mouse) dose-dependently induced amnesia. Pre-test administration of the same doses of ACPA and 8-OH-DPAT reversed the post-training ACPA- and 8-OH-DPAT-induced amnesia, respectively. This phenomenon has been named SDM. 8-OH-DPAT (1 μg/mouse) reversed the amnesia induced by ACPA (0.5, 1, and 2 ng/mouse) and induced ACPA SDM. ACPA (2 ng/mouse) reversed the amnesia induced by 8-OH-DPAT (0.25, 0.5, and 1 μg/mouse) and induced 8-OH-DPAT SDM. Pre-test administration of a 5-HT1A receptor antagonist, (S)-WAY 100,135 (0.25 and 0.5 μg/mouse), 5 min before ACPA and 8-OH-DPAT dose-dependently inhibited ACPA- and 8-OH-DPAT-induced SDM, respectively.The present study results demonstrated ACPA- and 8-OH-DPAT- induced SDM. Overall, the data revealed that dorsal hippocampal 5-HT1A receptor mechanisms play a pivotal role in modulating cross state-dependent memory retrieval between ACPA and 8-OH-DPAT.

A new arylsulfanyl-benzo-2,1,3-thiadiazoles derivative produces an anti-amnesic effect in mice by modulating acetylcholinesterase activity

The aim of the present study was investigate the binding affinity of 5-((4-methoxyphenyl)thio)benzo[c][1,2,5]thiadiazole (MTDZ) with acetylcholinesterase (AChE). We also evaluated the effect of MTDZ against scopolamine (SCO)-induced amnesia in mice and we looked at the toxicological potential of this compound in mice. The binding affinity of MTDZ with AChE was investigated by molecular docking analyses. For an experimental model, male Swiss mice were treated daily with MTDZ (10 mg/kg, intragastrically (i.g.)) or canola oil (10 ml/kg, i.g.), and induced, 30 min later, with injection of SCO (0.4 mg/kg, intraperitoneally (i.p.)) or saline (0.9%, 5 ml/kg, i.p.) daily. From day 1 to day 10, mice were submitted to the behavioral tasks (Barnes maze, open-field, object recognition and location, Y-maze and step-down inhibitory avoidance tasks), 30 min after induction with SCO. On the tenth day, the animals were euthanized and blood was collected for the analysis of biochemical markers (creatinine, aspartate (AST), and alanine (ALT) aminotransferase). MTDZ interacts with residues of the AChE active site. SCO caused amnesia in mice by changing behavioral tasks. MTDZ treatment attenuated the behavioral changes caused by SCO. In ex vivo assay, MTDZ also protected against the alteration of AChE activity, reactive species (RS) levels, thiobarbituric acid reative species (TBARS) levels, catalase (CAT) activity in tissues, as well as in transaminase activities of plasma caused by SCO in mice. In conclusion, MTDZ presented anti-amnesic action through modulation of the cholinergic system and provided protection from kidney and liver damage caused by SCO.

Protective Effects of Inosine on Memory Consolidation in a Rat Model of Scopolamine-Induced Cognitive Impairment: Involvement of Cholinergic Signaling, Redox Status, and Ion Pump Activities.

This study investigated the effects of inosine on memory acquisition and consolidation, cholinesterases activities, redox status and Na+, K+-ATPase activity in a rat model of scopolamine-induced cognitive impairment. Adult male rats were divided into four groups: control (saline), scopolamine (1mg/kg), scopolamine plus inosine (50mg/kg), and scopolamine plus inosine (100mg/kg). Inosine was pre-administered for 7days, intraperitoneally. On day 8, scopolamine was administered pre (memory acquisition protocol) or post training (memory consolidation protocol) on inhibitory avoidance tasks. The animals were subjected to the step-down inhibitory avoidance task 24hours after the training. Scopolamine induced impairment in the acquisition and consolidation phases; however, inosine was able to prevent only the impairment in memory consolidation. Also, scopolamine increased the activity of acetylcholinesterase and reduced the activity of Na+, K+-ATPase and the treatment with inosine protected against these alterations in consolidation protocol. In the animals treated with scopolamine, inosine improved the redox status by reducing the levels of reactive oxygen species and thiobarbituric acid reactive substances and restoring the activity of the antioxidant enzymes, superoxide dismutase and catalase. Our findings suggest that inosine may offer protection against scopolamine-induced memory consolidation impairment by modulating brain redox status, cholinergic signaling and ion pump activity. This compound may provide an interesting approach in pharmacotherapy and as a prophylactic against neurodegenerative mechanisms involved in Alzheimer's disease.

The neurotherapeutic role of a selenium-functionalized quinoline in hypothalamic obese rats.

Obesity is considered one of the major global health problems and increases the risk of several medical complications, such as diabetesand mental illnesses. The present study investigated the effect of 7-chloro-4-(phenylselanyl) quinoline (4-PSQ) on obesity parameters,behavioral and neurochemical alterations in hypothalamic obese rats. Male Wistar rats received subcutaneous neonatal injections of monosodiumglutamate (MSG, 4g/kg) or saline. After the Lee Index evaluation, rats were divided into groups and treated with 4-PSQ (5 mg/kg, intragastric route) orcanola oil once a day (post-natal days (PND) 60→76). Open-field, elevated plus-maze, forced swim task, object recognition/location memory, and stepdowninhibitory avoidance tasks were conducted from PND 66 to 74. On PND 76, rats were euthanized and epididymal fat, blood, cerebral cortex, andhippocampus were removed. Blood biochemical parameters and cortical/hippocampal acetylcholinesterase (AChE) and Na /K -ATPase activities wereassessed. MSG increased the Lee Index characterizing the chemically induced hypothalamic obesity model. 4-PSQ reversed the increases ofepididymal fat, blood glucose, and triglyceride levels caused by MSG exposure. 4-PSQ attenuated anxiety-like and depression-like behaviors induced byneonatal administrations of MSG. Memory deficits found in MSG-obese rats were reversed by treatment with 4-PSQ. Neurochemical alterations producedby MSG evidenced by stimulation ofNa+/K+-ATPase and AChE activities in the cerebral cortex and hippocampus of rats were normalized by 4-PSQtreatment. In brief, 4-PSQ therapy improved hypothalamic obesity-related parameters, as well as psychiatric symptoms, cognitive impairment,and neurochemical alterations found in obese rats.

Improved Spatial Memory And Neuroinflammatory Profile Changes in Aged Rats Submitted to Photobiomodulation Therapy.

Recent evidences have shown the therapeutic potential of transcranial photobiomodulation on traumatic brain injury and Alzheimer's disease. Despite the promising benefits in the brain, little is known about the laser's effects in the absence of pathological conditions. We submitted young (4months old) and aged (20months old) rats to transcranial low-level laser and evaluated their exploratory activity and habituation in open field, anxiety in elevated plus maze, spatial memory in Barnes maze, and aversive memory in a step-down inhibitory avoidance task. Additionally, the levels of a panel of inflammatory cytokines and chemokines were quantified in two different brain regions: the cerebral cortex and the hippocampus. Young and aged rats submitted to transcranial laser exhibited better cognitive performance in Barnes maze than did control rats. Transcranial laser therapy decreased cortical levels of GM-CSF, IL-10, MCP-1, LIX, and TNFα in young rats and IL-5 in aged rats. High levels of IL-6, IL-10, and TNF-alpha were found in the cerebral cortex of aged rats submitted to transcranial laser. In the hippocampus, a decrease in IP-10 and fractalkine levels was observed in the aged rats from the laser group when compared to the aged rats from the control group. Our data indicate that transcranial photobiomodulation improves spatial learning and memory and alters the neuroinflammatory profile of young and aged rats' brains.

Effect of a purine derivative containing selenium to improve memory decline and anxiety through modulation of the cholinergic system and Na+/K+-ATPase in an Alzheimer's disease model.

Alzheimer's disease (AD) is a worldwide problem, and there are currently no treatments that can stop this disease. To investigate the binding affinity of 6-((4-fluorophenyl) selanyl)-9H-purine (FSP) with acetylcholinesterase (AChE), to verify the effects of FSP in an AD model in mice and to evaluate the toxicological potential of this compound in mice. The binding affinity of FSP with AChE was investigated by molecular docking analyses. The AD model was induced by streptozotocin (STZ) in Swiss mice after FSP treatment (1mg/kg, intragastrically (i.g.)), 1st-10th day of the experimental protocol. Anxiety was evaluated in an elevated plus maze test, and memory impairment was evaluated in the Y-maze, object recognition and step-down inhibitory avoidance tasks. The cholinergic system was investigated based on by looking at expression and activity of AChE and expression of choline acetyltransferase (ChAT). We evaluated expression and activity of Na+/K+-ATPase. For toxicological analysis, animals received FSP (300mg/kg, i.g.) and aspartate aminotransferase, alanine aminotransferase activities were determined in plasma and δ-aminolevulinate dehydratase activity in brain and liver. FSP interacts with residues of the AChE active site. FSP mitigated the induction of anxiety and memory impairment caused by STZ. FSP protected cholinergic system dysfunction and reduction of activity and expression of Na+/K+-ATPase. FSP did not modify toxicological parameters evaluated and did not cause the death of mice. FSP protected against anxiety, learning and memory impairment with involvement of the cholinergic system and Na+/K+-ATPase in these actions.

Valerian treatment during the postpartum period alters breast milk composition and impairs long-term memory in female rat offspring.

Maternal anxiety symptoms in the perinatal period might have long-term health effects on both the mother and the developing child. Valerian is a phytotherapeutic agent that is widely used for the treatment of anxiety. This study investigated the effects of valerian treatment in postpartum rats on maternal care, toxicity, and milk composition. Postnatal development, memory, and anxiety behavior in the offspring were also assessed. Postpartum Wistar rats received the valerian (500, 1000, or 2000 mg·kg-1·day-1) by oral gavage. Clinical and biochemical toxicity was evaluated with commercial kits. Maternal behavior was observed daily. Milk composition was analyzed by colorimetric methods. Physical and neuromotor tests were used to analyze postnatal development. Anxiolytic activity was assessed by the elevated plus maze, and memory was evaluated by the step-down inhibitory avoidance task. Maternal toxicity and care behavior were not altered by the treatment, while only the highest dose promoted a significant increase of lactose, and the doses 1000 and 2000 mg·kg-1·day-1 promoted a reduction of protein contents in milk. Postnatal development was similar in all offspring. Adult offspring did not display altered anxiety behavior, while long-term memory was impaired in the female adult offspring by maternal treatment with 1000 mg·kg-1·day-1. These results suggested that high doses of valerian had significant effects on important maternal milk components and can cause long-term alterations of offspring memory; thus, treatment with high doses of valerian is not safe for breastfeeding Wistar rat mothers.

Amnesia-ameliorative effect of a quinoline derivative through regulation of oxidative/cholinergic systems and Na+/K+-ATPase activity in mice.

The present study evaluated the anti-amnesic activity of 1-(7-chloroquinolin-4-yl)-5-methyl-N-phenyl-1H-1,2,3-triazole-4-carboxamide (QTCA-1) against scopolamine (SCO)-induced amnesia in mice. It was evaluated cholinergic dysfunction, oxidative stress and Na+/K+-ATPase activity in cerebral cortex and hippocampus of mice. Male Swiss mice were treated with QTCA-1 (10mg/kg, intragastrically (i.g.), daily) for nine days. Thirty minutes after the treatment with compound, the animals received a injection of SCO (0.4mg/kg, intraperitoneally (i.p.)). Mice were submitted to the behavioral tasks 30min after injection of SCO (Barnes maze, open-field, object recognition and location, and step-down inhibitory avoidance tasks) during nine days. In day 9, cerebral cortex and hippocampus of mice were removed to determine the thiobarbituric acid reactive species (TBARS) levels, and catalase (CAT), Na+/K+-ATPase and acetylcholinesterase (AChE) activities. SCO caused amnesia in mice for changing in step-down inhibitory avoidance, Barnes maze, and object recognition and object location tasks. QTCA-1 treatment attenuated the behavioral changes caused by SCO. Moreover, SCO increased AChE and CAT activities, decreased Na+/K+-ATPase activity and increased TBARS levels in the cerebral structures of mice. QTCA-1 protected against these brain changes. In conclusion, QTCA-1 had anti-amnesic action in the experimental model used in the present study, through the anticholinesterase effect, modulation of Na+/K+-ATPase activity and antioxidant action.

Possible interaction between the ventral hippocampal cannabinoid CB2 and muscarinic acetylcholine receptors on the modulation of memory consolidation in mice.

To clarify possible interaction between the ventral hippocampal cannabinoid CB2 receptors and the cholinergic system in control of the memory process, the effects of cannabinoid and acetylcholine receptor agents on memory consolidation have been investigated in mice. Animals implanted with bilateral cannulas at the CA3 region of the ventral hippocampus and microinjected with scopolamine and cannabinergic agents. These animals were tested using a one-trial step-down inhibitory avoidance task. The results indicated impairment of memory consolidation by posttraining intra-CA3 microinjection of scopolamine (1 and 2 µg/mouse). Nevertheless, coinjection of various doses of scopolamine (0.01, 1 and 2 µg/mouse) with an ineffective dose of AM630 (1 µg/mouse) or GP1a (1 µg/mouse) did not show any significant effect on deficiency of memory consolidation produced by scopolamine. Posttraining application of cannabinoid CB2 receptor antagonist, AM630 (1, 10 and 100 µg/mouse; intra-CA3) alone had no significant influence on memory performance, but its coinjection with significant dose of scopolamine (1 µg/mouse) decreased memory consolidation. Moreover, posttraining injection of GP1a, cannabinoid CB2 receptor agonist, (10 and 100 µg/mouse; intra-CA3) decreased memory consolidation. Posttraining coadministration of diverse doses of GP1a (1, 10 and 100 µg/mouse; intra-CA3) with an effective dose of scopolamine (1 µg/mouse) meaningfully increased deficiency of memory consolidation produced by GP1a (100 µg/mouse). In addition, all drugs had no significant effect on locomotion. Consequently, these results propose that a probable interaction between the CA3 cannabinoid CB2 receptors and muscarinic acetylcholine receptors (mAChR) modulates memory consolidation process in mice.

Ammonia exposition during gestation induces neonatal oxidative damage in the brain and long-term cognitive alteration in rats.

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.

Repeated Methylglyoxal Treatment Depletes Dopamine in the Prefrontal Cortex, and Causes Memory Impairment and Depressive-Like Behavior in Mice.

Methylglyoxal (MGO) is a highly reactive dicarbonyl molecule that promotes the formation of advanced glycation end products (AGEs), which are believed to play a key role in a number of pathologies, such as diabetes, Alzheimer's disease, and inflammation. Here, Swiss mice were treated with MGO by intraperitoneal injection to investigate its effects on motor activity, mood, and cognition. Acute MGO treatment heavily decreased locomotor activity in the open field test at higher doses (80-200mg/kg), an effect not observed at lower doses (10-50mg/kg). Several alterations were observed 4 h after a single MGO injection (10-50mg/kg): (a) plasma MGO levels were increased, (b) memory was impaired (object location task), (c) anxiolytic behavior was observed in the open field and marble burying test, and (d) depressive-like behavior was evidenced as evaluated by the tail suspension test. Biochemical alterations in the glutathione and glyoxalase systems were not observed 4h after MGO treatment. Mice were also treated daily with MGO at 0, 10, 25 and 50mg/kg for 11 days. From the 5th to the 11th day, several behavioral end points were evaluated, resulting in: (a) absence of motor impairment as evaluated in the open field, horizontal bars and pole test, (b) depressive-like behavior observed in the tail suspension test, and (c) cognitive impairments detected on working, short- and long-term memory when mice were tested in the Y-maze spontaneous alternation, object location and recognition tests, and step-down inhibitory avoidance task. An interesting finding was a marked decrease in dopamine levels in the prefrontal cortex of mice treated with 50mg/kg MGO for 11days, along with a ~ 25% decrease in the Glo1 content. The MGO-induced dopamine depletion in the prefrontal cortex may be related to the observed memory deficits and depressive-like behavior, an interesting topic to be further studied as a potentially novel route for MGO toxicity.

Cross state-dependency of learning between 5-HT1A and/or 5-HT7 receptor agonists and muscimol in the mouse dorsal hippocampus.

Dysfunction of the serotonergic and GABAergic systems in cognitive disorders has been revealed. Understanding the neurobiological mechanisms of drug-associated learning and memory formation may help treatment of cognitive disorders. The aim of the present study was to investigate: 1) 8-OH-DPAT (5-HT1A agonist), AS19 (5-HT7 agonist) and muscimol (GABA-A agonist) on memory retrieval and state of memory, 2) cross state-dependent learning between 8-OH-DPAT and/or AS19 and muscimol. The dorsal hippocampal CA1 regions of adult male NMRI mice were bilaterally cannulated, and all drugs were microinjected into the intended sites of injection. A single-trial step-down inhibitory avoidance task was used for the evaluation of memory retrieval and state of memory. Post-training and/or pre-test 8-OH-DPAT, AS19 and muscimol induced amnesia. Pre-test microinjection of the same doses of 8-OH-DPAT, AS19 and muscimol reversed the post-training 8-OH-DPAT-, AS19- and muscimol-induced amnesia, respectively. This event has been named state-dependent learning (SDL). The amnesia induced by 8-OH-DPAT was reversed by muscimol and induced 8-OH-DPAT SDL. The amnesia induced by muscimol was reversed by 8-OH-DPAT and induced muscimol SDL. The amnesia induced by AS19 was reversed by muscimol and induced AS19 SDL. The amnesia induced by muscimol was reversed by AS19 and induced muscimol SDL. Pre-test administration of a selective GABA-A receptor antagonist, bicuculline, 5 min before muscimol, 8-OH-DPAT and AS19 dose-dependently inhibited muscimol-, 8-OH-DPAT- and AS19-induced SDL, respectively. The results strongly revealed a cross SDL among 8-OH-DPAT and/or AS19 and muscimol in the dorsal hippocampal CA1 regions.

C-glycosyl flavonoid orientin alleviates learning and memory impairment by radiofrequency electromagnetic radiation in mice via improving antioxidant defence mechanism

Objective: To investigate the antioxidant efficacy of oral orientin on 900 MHz radiofrequency-electromagnetic radiation-induced oxidative stress in mice. Methods: The mice were randomly allotted into 5 groups consisting of 7 mice each. The deionised water and radiofrequency electromagnetic radiations (RF-EMR) groups were administered with deionised water while orientin was administered to the RF-EMR + low dose of orientin group (10 mg/kg), RF-EMR + high dose of orientin group (20 mg/kg) and high dose of orientin group (20 mg/kg). All the groups except deionised water and high dose groups were exposed to 900 MHz radiofrequency-electromagnetic radiation for 28 consecutive days (1 h/day). Learning and memory was assessed via the step-down inhibitory avoidance task. Activities of lipid prexidation and antioxidant enzymes were measured using kits. Results: Radiofrequency electromagnetic radiation caused impairment in learning and memory and reduced activities of brain antioxidant enzymes, increased lipoperoxidation and corticosterone concentration as well as histopathological aberrations in the hippocampal tissues. Conversely, orientin alleviated learning and memory deficit, improved the activities of endogenous antioxidant enzymes and mitigated brain lipoperoxidation and neuronal degeneration in mice exposed to radiofrequency electromagnetic radiation. Conclusions: Orientin alleviates learning and memory impairment due to radiofrequency electromagnetic radiation in mice by improving antioxidant defence mechanism and may be considered as a promising therapeutic agent for improving the antioxidant system of people living in radiofrequency electromagnetic radiation-prone environment.

Neuroprotective effects of 1`δ-1`-acetoxyeugenol acetate on Aβ(25-35) induced cognitive dysfunction in mice

The progressive accumulation of amyloid beta (Aβ) peptide is neurotoxic and leads to Alzheimer’s type dementia. Accumulation of Aβ has been associated with dysfunction of hypothalamic-pituitary-adrenal (HPA) axis and elevated pro-inflammatory cytokines. In this study, we investigated the effect of 1`δ-1`-acetoxyeugenol acetate (DAEA), isolated from Alpinia galanga (L.), on Aβ(25–35) induced neurodegeneration in mice. Mice were treated with three different doses of DAEA (12.5 mg/kg, 25 mg/kg and 50 mg/kg) for 28 days. Aβ(25–35) was injected by intracerebroventricular (i.c.v.) injection on the 15th day of 28 days. Open field, water maze and step-down inhibitory tests were performed on the 27th day to determine the habituation memory, spatial learning, and short- and long-term memory, respectively. Acetylcholinesterase (AChE), Corticosterone, biogenic amines (serotonin and dopamine), tumour necrosis factor-α (TNF-α), and antioxidant parameters such as superoxide dismutase, catalase, glutathione peroxidase and vitamin C were evaluated in brain homogenates after behavioural tests to ascertain the cognitive improvement through neuro-immune-endocrine modulation. The DAEA treatment with 25 mg/kg and 50 mg/kg resulted in significant (p < 0.001) improvement of habituation memory and step-down inhibitory avoidance task. In spatial learning, the cognitive improvement was significantly improved (p < 0.001) by reduction in escape latency. In the biochemical study, the significant (p < 0.001) reduction of AChE indicates the preeminent neuroprotection. Corticosterone and TNF-α were significantly (p < 0.01) reduced and biogenic amines were increased with antioxidant markers, which signify the potential influence of DAEA on neuroprotection. Our investigation revealed that the drug DAEA attenuates stress mediated through the HPA axis and regulates the neuroendocrine and neuroimmune function to improve the cognition. DAEA could be a potential lead candidate for the treatment of neurodegeneration.

The effect of CA1 dopaminergic system on amnesia induced by harmane in mice.

In the present study, the effects of bilateral injections of dopaminergic drugs into the hippocampal CA1 regions (intra-CA1) on harmane-induced amnesia were examined in mice. We used a single-trial step-down inhibitory avoidance task for the assessment of memory acquisition in adult male mice. Our data indicated that pre-training intra-peritoneal (i.p.) administration of harmane (12mg/kg) impaired memory acquisition. Moreover, intra-CA1 administration of dopamine D1 receptor agonist, SKF38393 (0.25µg/mouse), dopamine D1 receptor antagonist, SCH23390 (0.25µg/mouse), dopamine D2 receptor agonist, quinpirole (0.125 and 0.25µg/mouse) and dopamine D2 receptor antagonist, sulpiride (0.2 and 0.4µg/mouse) decreased the learning of a single-trial inhibitory avoidance task. Furthermore, pre-training intra-CA1 injection of sub-threshold doses of SKF38393 (0.0625µg/mouse) or sulpiride (0.1µg/mouse) increased pre-training harmane (4 and 8mg/kg, i.p.)-induced amnesia. On the other hand, pre-training intra-CA1 injection of a sub-threshold dose of SCH23390 (0.0625µg/mouse) reversed amnesia induced by an effective dose of harmane (12mg/kg; i.p.). In addition, Pre-training intra-CA1 injection of quinpirole (0.0625µg/mouse) had no effect on memory impairment induced by harmane. These findings indicate the involvement of CA1 dopaminergic system on harmane-induced impairment of memory acquisition.

Low arsenic concentrations impair memory in rat offpring exposed during pregnancy and lactation: Role of α7 nicotinic receptor, glutamate and oxidative stress

Inorganic arsenic (iAs) is an important natural pollutant. Millions of individuals worldwide drink water with high levels of iAs. Arsenic exposure has been associated to cognitive deficits. However, the underlying mechanisms remain unknown. In the present work we investigated in female adult offspring the effect of the exposure to low arsenite sodium levels through drinking water during pregnancy and lactation on short- and long-term memory. We also considered a possible underlying neurotoxic mechanism. Pregnant rats were exposed during pregnancy and lactation to environmentally relevant iAs concentrations (0.05 and 0.10 mg/L). In 90-day-old female offspring, short-term memory (STM) and long-term memory (LTM) were evaluated using a step-down inhibitory avoidance task. In addition, we evaluated the α7 nicotinic receptor (α7-nAChR) expression, the transaminases and the oxidative stress levels in hippocampus. The results showed that the exposure to 0.10 mg/L iAs in this critical period produced a significant impairment in the LTM retention. This behavioral alteration might be associated with several events that occur in the hippocampus: decrease in α7-nAChR expression, an increase of glutamate levels that may produce excitotoxicity, and a decrease in the antioxidant enzyme catalase (CAT) activity.

Protective effects of banana pectin against aluminum-induced cognitive impairment and aluminum accumulation in mice

To investigate the effect of pectin on absorption and bio-toxicity of aluminum, pectin extract (100 mg kg−1 d−1) from banana pulp was orally administrated to aluminum exposed mice (35 mg kg−1 d−1) for 6 weeks. Our result showed that body weight gain of the mice treated with aluminum plus banana pectin was 32.5% higher than that of mice exposed to aluminum alone after 6 weeks of the administration. In both the step-down inhibitory avoidance task and Morris water maze test, memory retention of aluminum-exposed mice was significantly improved by the pectin administration. Treatment with banana pectin effectively prevented absorption of aluminum from the gastrointestinal tract, total aluminum excretion of mice treated with banana pectin plus aluminum was 9.3% higher than that of mice exposed to aluminum alone on the 12th day. Aluminum level in serum, cerebrum, or cerebellum of mice treated with aluminum plus banana pectin was 30.8%, 17.5%, or 17.9% lower than that of mice exposed to aluminum alone on the 42nd day, respectively. In conclusion, banana pectin extract can effectively reduce aluminum toxicity in mice.

Taraxerol as a possible therapeutic agent on memory impairments and Alzheimer’s disease: Effects against scopolamine and streptozotocin-induced cognitive dysfunctions

Alzheimer’s disease (AD) is a neurodegenerative disorder associated with cognitive impairment and cholinergic neuronal death, characteristic of the effect of time on biochemical neuronal function. The use of medicinal plants as an alternative form of prevention, or even as a possible treatment of AD, is therefore interesting areas of research, since the standard drugs have many side effects. Taraxerol (TRX) is a triterpene that has been isolated from several plant species, and its various pharmacological properties have already been identified, such the acetylcholinesterase (AChE) inhibition activity in vitro. There is a lack of information in literature that confirms the effect of TRX in an animal AD-like model. Seeking to fill this gap in the literature, in the present work we assessed the effect of TRX on AChE activity in the animals’ encephalon and hippocampus. We also investigated the effect of TRX (1.77 µM/side, 0.5 μL) isolated from leaves of Eugenia umbelliflora Berg. on aversive memory impairments induced by scopolamine (2 µg/side, 0.5 µL) infused into rat hippocampus, and the effect of TRX (0.89 and 1.77 µM/side, 0.5 μL) on aversive memory impairments induced by streptozotocin (STZ) (2.5 mg/mL, 2.0 µL) infused i.c.v. into mice, using the step-down inhibitory avoidance task. We found that TRX significantly inhibited AChE activity in the animal’s hippocampus. Furthermore, TRX significantly improved scopolamine and STZ-induced memory impairment. Taking together, these results confirms its AChE activity inhibition in animals and indicate that TRX has anti-amnesic activity that may hold significant therapeutic value in alleviating certain memory impairments observed in AD.

Prior Learning of Relevant Nonaversive Information Is a Boundary Condition for Avoidance Memory Reconsolidation in the Rat Hippocampus.

Reactivated memories can be modified during reconsolidation, making this process a potential therapeutic target for posttraumatic stress disorder (PTSD), a mental illness characterized by the recurring avoidance of situations that evoke trauma-related fears. However, avoidance memory reconsolidation depends on a set of still loosely defined boundary conditions, limiting the translational value of basic research. In particular, the involvement of the hippocampus in fear-motivated avoidance memory reconsolidation remains controversial. Combining behavioral and electrophysiological analyses in male Wistar rats, we found that previous learning of relevant nonaversive information is essential to elicit the participation of the hippocampus in avoidance memory reconsolidation, which is associated with an increase in theta- and gamma-oscillation power and cross-frequency coupling in dorsal CA1 during reactivation of the avoidance response. Our results indicate that the hippocampus is involved in memory reconsolidation only when reactivation results in contradictory representations regarding the consequences of avoidance and suggest that robust nesting of hippocampal theta-gamma rhythms at the time of retrieval is a specific reconsolidation marker.SIGNIFICANCE STATEMENT Posttraumatic stress disorder (PTSD) is characterized by maladaptive avoidance responses to stimuli or behaviors that represent or bear resemblance to some aspect of a traumatic experience. Disruption of reconsolidation, the process by which reactivated memories become susceptible to modifications, is a promising approach for treating PTSD patients. However, much of what is known about fear-motivated avoidance memory reconsolidation derives from studies based on fear conditioning instead of avoidance-learning paradigms. Using a step-down inhibitory avoidance task in rats, we found that the hippocampus is involved in memory reconsolidation only when the animals acquired the avoidance response in an environment that they had previously learned as safe and showed that increased theta- and gamma-oscillation coupling during reactivation is an electrophysiological signature of this process.