Passive Avoidance Apparatus Research Articles

Probiotics Mitigate Exercise Fatigue, Memory Deficits, Depression and Neuro/inflammation in a Mouse Model of Gulf War Illness

We have previously found learning/memory, exercise intolerance, metabolic disturbance, gut dysbiosis and deregulation of neuroinflammatory genes, suggesting a possible microbiota-gut-brain interaction in GWI pathology (Kozlova et al., 2022a PMID: 34710444; 2022b PMID: 34801513). Here, we tested the hypothesis that probiotic treatment (P) prevents GWI symptoms. Adult male C57Bl/6N mice were separated into 4 groups (n=16/group): GW receiving pyridostigmine bromide (8.7 mg/kg, PB, po), permethrin (1.3 mg/kg, PER, top), DEET (33%, top); CON/S (vehicle plus stress); CON/S+P and GW+P. Probiotic groups received a gut-protective probiotic (P) cocktail of L. reuteri, L. rhamnosus, L. casei, B. longum (po, 108 CFU/mL, 3 times/wk) for 2 wk prior to and during GW agent treatment and until sacrifice 5 months later. Fecal RT-qPCR showed colonization of all strains except L. rhamnosus after 6-7 doses when compared to saline sham. Colonization after GW agent exposure was strain-specific and varied with time post-exposure. On an exercise endurance (EE) test GW (but not GW+P) mice tired faster relative to CON/S at PT56 (p<0.05) but not at PT150. Repeat testing on the passive avoidance apparatus (15 wk after previous test) showed that GW but not GW+P mice displayed reduced latency to enter aversive chamber on day 1 of acquisition trials, indicating deficient memory (p<0.05). Depressive-like behavior (mean percent time spent mobile) on tail suspension test (TST) showed less time spent mobile for GW (p<0.05) but not GW+P mice than controls at PT50 (but not PT150). Probiotics protected against the GW-induced rise in liver C-reactive protein (CRP) (p<0.05) and brain interleukin-6 (IL-6) (p<0.05). Immunofluorescence probing in the hippocampal CA1 and dentate gyrus showed significantly greater counts of Iba-1 positive cells in GW (but not GW+P) vs CON/S (p<0.05). NeuN immunostaining on the same sections showed abnormal neuronal phenotype indicative of reorganized RNA in GW but not GW+P) vs CON/S (p<0.05). Multi-gene profiling of innate and adaptive immunity genes in brain homogenates (prefrontal cortex, hypothalamus, hippocampus) identified GW agent-induced deregulation (>1.5-fold; p<.05) of pro-inflammatory genes, i.e., upregulation of C5ar1 and Cxcl10 and downregulation of Tlr4; changes prevented by probiotic treatment. In the gut, M1 proinflammatory macrophages appeared to be more abundant in GW (but not GW+P) vs CON/S (p<0.05). We used 16S next generation sequencing to examine probiotic treatment effects on gut microbial communities. In combination, our findings indicate that GW mice can be used to model multi-symptom illness and support previous evidence that the underlying pathophysiology in GWI likely involve systemic, gut and neuroinflammation and bacterial dysbiosis. Importantly, we show for the first time that probiotic treatment protects against some GWI symptom domains. Further study is needed to uncover pathophysiological pathways through which the microbiota-gut-brain axis impacts gut and brain health and toxicant-related pathology. DoD grant GW-180072 to M.C.C. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

The effect of modafinil on passive avoidance memory, brain level of BDNF and oxidative stress markers in sepsis survivor rats

Propose/aim of study: Modafinil (MD) is a psychostimulant drug used off-label and cognitive dysfunction may be a significant emerging treatment target for this drug. The objective of this study was to evaluate the effect of MD on the neurochemical parameters and memory impairment of rats submitted to sepsis by cecal ligation and perforation (CLP). Material and method: Male Wistar rats (250–350g) were submitted to CLP, or sham as control, and divided into the sham + water, sham + MD (300 mg/kg), CLP + water, and CLP + MD (300 mg/kg) groups. Ten days after the administration of MD and CLP, the rats were submitted to a memory test by passive avoidance apparatus being sacrificed. The nitrite and nitrate (N/N) concentration, myeloperoxidase (MPO) and catalase (CAT) activity, lipid and protein oxidative damage, and brain-derived neurotrophic factor (BDNF) levels were measured in the prefrontal cortex and hippocampus. Results: The passive avoidance test verified an increase in the latency time compared training and test section in the groups sham + water and CLP + MD. Decreased N/N concentration and MPO activity were verified in the prefrontal cortex of rats submitted to CLP and MD treatment, as well as reduced protein and lipid oxidative damage in the hippocampus, which was accompanied by increased CAT activity and BDNF levels.Conclusion: Our data indicate the role of MD in attenuating oxidative stress parameters, the alteration of BDNF, and an improvement in memory impairment in rats ten days after induction of sepsis.

Protective Effects of N-Acetylcysteine on Dipentyl Phthalate Induced Cognitive Dysfunction and Brain Oxidative Stress in Mice

Background: Dipentyl phthalate (DPeP) is a plasticizer compound commonly used in polyvinylchloride plastic to enhance softness and flexibility. They are not bound covalently to plastic polymers; therefore, they can dissolve into the environment and adversely affect the health of humans and animals.
 Objectives: The aim of this study was to investigate the effect of DPeP on cognition and protective effects of N-acetylcysteine (NAC) on DPeP induced alteration in cognitive behaviour and oxidative stress markers in mice.
 Methods: Mice were orally treated with 2 doses (33 mg/kg and 100 mg/kg) of DPeP for 28 days. Cognitive functions were assessed using spatial navigation tasks on the Morris water maze and the step-down latency in the passive avoidance apparatus. Oxidative stress was assessed by examining the levels of malondialdehyde, glutathione, ferric reducing antioxidant power, and 8-hydroxy-deoxyguanosine levels in the whole brain of mice.
 Results: There was a significant increase in latency in spatial navigation tasks and a significant decline in the step-down latency in passive avoidance apparatus in the DPeP-treated group compared to the control groups. There was also a significant increase in the levels of oxidative stress following DPeP administration as seen with the rise in the levels of malondialdehyde, 8-hydroxy-deoxyguanosine, and a fall in glutathione and ferric reducing antioxidant power levels.
 Conclusion: The present study demonstrated that DPeP adversely affects learning and memory functions in mice by oxidative stress-mediated neuronal damage. These effects were attenuated by pretreatment with N-acetylcysteine.

Pharmacological Investigations of Selected Multitarget‐Direct Ligands for the Treatment of Alzheimer's Disease

AbstractAlzheimer's disease (AD) is a complex, degenerative condition linked to memory loss and cognitive degradation. The phenyl sulfonyl‐pyrimidine derivatives containing dimethoxy‐chloro substituent (BS‐10 and BS‐22) were previously recognized as multitarget‐directed ligands (MTDLs) due to their ability to inhibit acetylcholinesterase (AChE) at low nanomolar concentrations (IC50=47.33±0.02 and 51.36±0.04 nM respectively) while also reducing amyloid beta (Aβ) aggregation. In the current investigation, we investigated the in vivo and ex‐vivo effects of BS‐10 and BS‐22 chemicals on cognition and the cholinergic system. We have used scopolamine and Aβ1‐42 models of cognitive impairment which were measured during Y‐maze and passive avoidance apparatus. Results showed that BS‐10 at 10 mg/kg compared to BS‐22 at 20 mg/kg rescued memory impairment more significantly. Moreover, ex‐vivo and biochemical studies exhibited both compounds improved the hippocampal acetylcholine (Ach) level by reducing AChE activity as well as antioxidant properties. In addition, BS‐10 and BS‐22 attenuated Aβ1‐42 induced cognitive deficiency in rats during Y‐maze tests and significantly restored mitochondrial membrane potential and reduced the tau protein level in rats (p<0.05). In summary, our results indicated that MTDLs BS‐10 and BS‐22 would be a promising therapeutic approach in AD.

ATTENUATION OF OXIDATIVE STRESS AND NEUROTOXICITY BY MK-801 (DIZOCILPINE) ON DIPENTYLPHTHALATE-INDUCED COGNITIVE DYSFUNCTION IN MICE

Objectives: The aim of our research is to study the effect of dipentylphthalate (DPeP), a plasticizer on cognition and various oxidative stress markers in mice, and to explore the modulatory effects of MK-801. Methods: In the present study, experimental mice were orally treated with two doses (33 and 100 mg/kg) of DPeP for 28 days. Cognitive functions were assessed using spatial navigation task on Morris water maze (MWM) and step-down latency (SDL) in passive avoidance apparatus. Oxidative stress was assessed by examining the levels of malondialdehyde (MDA), glutathione (GSH), ferric-reducing antioxidant power (FRAP), and 8-hydroxy-deoxyguanosine (8-OH-dG) levels in whole brain of mice. Results: DPeP exposure led to a statistically significant increase of latency in spatial navigation task and significant decline in the SDL in passive avoidance apparatus when compared to the control groups. Oxidative stress markers showed a significant increase following DPeP administration as seen with rise in levels of MDA, 8-OH-dG, and a fall in GSH and FRAP levels. Conclusion: The present data suggest that DPeP could adversely affect learning and memory functions in mice by an oxidative stress-mediated neuronal damage and pre-administration of MK-801 has the potential to attenuate these effects.

Astaxanthin, a carotenoid antioxidant, pretreatment alleviates cognitive deficits in aircraft noised mice by attenuating inflammatory and oxidative damage to the gut, heart and hippocampus

BackgroundWe first explore whether aircraft noise (AN) induces cognitive deficit via inducing oxidative damage in multiple vital organs including intestines, hearts and hippocampus tissues. Second, we explore whether the AN-induced cognitive deficits and inflammatory and oxidative damage to multiple organs can be alleviated by Astaxanthin (AX) pretreatment. MethodsCognitive deficits were induced by subjecting the mice to AN 2 h daily for 7 consecutive days. An intragastrical dose of AX emulsifier (at the dose of daily feed intake [6 g] of a mouse three times weekly) was given to mice for consecutive 8 weeks prior to the start of AN. Cognitive functions were evaluated by using passive avoidance apparatus, Y-maze, Morris water maze and novel recognition test. Intestinal permeability was determined by measuring the intestinal clearance of fluorescein-isothiocyante. Evans Blue extravasation assay was used to measure the permeability of blood-brain-barrier. Inflammatory and oxidative damage to multiple organs were determined by measuring several pro-inflammatory cytokines and oxidative stress indicators in intestines; hearts and hippocampus. ResultsMice treated with AN displayed exacerbated stress reactions, cognitive deficits, gut barrier hyperpermeability, increased upload of lipopolysaccharide translocation, systemic pro-inflammatory cytokines overproduction, blood-brain-barrier hyperpermeability, hippocampal neuroinflammation and increased levels of oxidative stress indicators in intestine, heart and hippocampus. All of the above-mentioned disorders caused by AN were significantly (P < 0.05) reversed by AX. ConclusionsOur data indicate that AX pretreatment alleviates cognitive deficits in aircraft noised mice by attenuating inflammatory and oxidative damage to intestines, hearts and hippocampal tissues.

Sea Cucumber-Derived Peptide Attenuates Scopolamine-Induced Cognitive Impairment by Preventing Hippocampal Cholinergic Dysfunction and Neuronal Cell Death.

The incidence of neurodegenerative diseases related to cognitive decline and memory loss is on the rise as the global elderly population increases. In this study, we evaluated the effect of the sea cucumber-derived peptide Phe-Tyr-Asp-Trp-Pro-Lys (FYDWPK) on scopolamine-induced neurotoxicity in an animal model. The Morris water maze, passive avoidance apparatus, and shuttle box test were used to assess learning and memory abilities. In behavioral tests, FYDWPK effectively alleviated learning and memory impairment. FYDWPK also alleviated cholinergic dysfunction in mice with dementia. Furthermore, FYDWPK significantly improved oxidative imbalance by increasing superoxide dismutase activity and decreasing malondialdehyde levels (P < 0.05). The pathological results showed that FYDWPK alleviated neuronal loss, blurred caryotheca, and pyknotic nuclei in the hippocampus, and a high dose of FYDWPK had the best effect. In conclusion, FYDWPK alleviated cognitive and memory impairments by regulating oxidative imbalance, reducing cholinergic dysfunction, and relieving pathological alterations.

Investigation of nootropic potential of ethanol extract of Elettaria cardamomum Maton fruit (Cardamom): a spice of India

BackgroundCognitive impairment mainly affects learning and problem solving abilities of the person. Traditional medicines, due to fewer side effects, more efficacy and lesser cost are still the choice of treatment in India. The main objective of the present study is to explore the nootropic potential of ethanol extract of Elettaria cardamomum Maton fruits. The present study was conducted by using exteroceptive behavioral models like elevated plus maze, passive avoidance apparatus and object recognition task at doses 100, 300 and 500 mg/kg.ResultsEthanol extract of E. cardamomum fruits significantly decreased transfer latency and increased step down latency and discrimination index respectively when compared to normal control groups. Piracetam and diazepam exhibited respective rise and fall in memory of the animals. The effect of plant extract on total serum cholesterol, acetylcholinesterase and malondialdehyde were more effective at two higher doses. However, it decreased serum glucose levels insignificantly whereas a significant rise in brain GSH levels was observed with increasing dose of the extract.ConclusionsThe study concludes that the nootropic effect of ethanol extract may be attributable to its anti-oxidant, anti-cholinesterase and cholesterol as well as glucose lowering potential.

The Effects of Ripe Pistachio Hulls Hydroalcoholic Extract and Aerobic Training on Learning and Memory in Streptozotocin-induced Diabetic Male Rats.

Introduction:Diabetes mellitus has harmful effects on body functions, such as learning and memory. According to the role of exercise and medicinal plants on body health, the purpose of this study was to survey the effect of combined aerobic training and the use of Ripe Pistachio Hulls (RPH) hydro-alcoholic extract on learning and memory in streptozotocin-induced diabetic male rats.Methods:In this experimental study, 42 male Wistar rats weighing 250–280 g were used in 6 groups with an equal number of 7 rats in each one. Streptozotocin (STZ) (50 mg / kg)was used to induce diabetes, and the test protocol was applied for 8 weeks. Passive avoidance memory was assessed using a step-through passive avoidance apparatus (shuttle box). SPSS software was used to analyze the data and P<0.05 was significant.Results:The results showed that step-through latency in the acquisition trial (STLa) was not significantly different among groups. Step-through latency in retrieval (STLr 24) test significantly reduced and time spent in The Dark Compartment (TDC) decreased in treated groups compared with the diabetic control groups (P<0.001). Also, there was no significant difference between the STZ and saline diabetic groups.Conclusion:The findings of this study revealed that the RPH hydro-alcoholic extract and aerobic exercise could improve passive avoidance memory in streptozotocin diabetic rats. Meanwhile, they might be an adjuvant therapy combined with other traditional medicine.

Protective Effect of Naringin on Bisphenol A-Induced Cognitive Dysfunction and Oxidative Damage in Rats.

Bisphenol A (BPA) is one of the highest volume chemicals produced worldwide, which is used in many plastic industries. The present study aimed to evaluate the effect of BPA on cognitive functions and oxidative stress, and determine whether the naringin (NG) co-administration can modify the effect of this compound on cognitive functions and inhibit any possible oxidative stress in the brain tissue of rats. Adult male Wistar rats were divided into six groups. Group I: control, Group II: BPA-treated rats (50 mg/kg/day), Group III, IV, V: BPA+NG (40, 80, 160 mg/kg/day), Group VI: NG (160 mg/kg/day) alone. Cognitive functions were evaluated using step-down latency (SDL) on a passive avoidance apparatus, and transfer latency (TL) in elevated plus-maze. A significant decrease in SDL, prolongation of TL, noticeable oxidative impairment and increase in acetylcholinesterase activity were observed in the BPA-treated in comparison with the control group. Also, the co-administration of NG (160 mg/kg) antagonized the effect of BPA on SDL and TL, attenuated oxidative damage by lowering malondialdehyde and nitrite concentrations and restored superoxide dismutase, catalase, and glutathione S-transferase activities. On the other hand, acetylcholinesterase activity was reduced in the groups co-administred with NG (80 or 160 mg/kg) and BPA in comparison with the BPA alone-treated group. The present study highlighted the therapeutic potential of NG against BPA-induced cognitive impairment and oxidative damage.

Evaluation of antioxidant potential of Emblica officinalis and Murraya koenigii and their role in modulation of cognitive function in diabetic rats

Background: Hyperglycaemia and hyperlipidaemia seen in diabetes mellitus result in oxidative stress and pose significant risk of cognitive decline that may lead to Alzheimer’s disease. Approved anti-diabetic drugs have so far failed to demonstrate anti-oxidant and anti-hyperlipidemic activity, apart from saroglitazar. Therefore, this study was done to find a suitable anti-diabetic drug that possesses anti-hyperglycaemic, anti-oxidant and anti-hyperlipidemic activities and can reverse cognitive decline.Methods: Emblica officinalis (250 mg/kg, p.o. and 500 mg/kg, p.o.) and Murraya koenigii (250 mg/kg, p.o. and 500 mg/kg, p.o.) were chosen to study these activities in Wistar rats. Diabetes was induced by single intraperitoneal injection of streptozotocin [STZ] (50 mg/kg). Fasting blood glucose levels and lipid profile were measured on day 1 and day 30 of the experiment. Cognitive function was assessed by measuring transfer latency (TL) on elevated plus maze, step-down latency (SDL) on passive avoidance apparatus and retention latency (RL) and quadrant time (QT) in Morris water maze. Oxidative stress was assessed at end of study by measuring brain MDA and GSH levels. Cholinergic marker of cognition, AChE was measured in brain at end of study.Results: Both E. officinalis and M. koenigii showed dose dependent anti-hyperglycemic, anti-hyperlipidemic and anti-oxidant effects in diabetic rats with 500 mg/kg dose showing significantly higher effect. Both 250 mg/kg and 500 mg/kg dose of E. officinalis and M. koenigii partially reversed cognitive decline in diabetic rats by day 30.Conclusions: 500 mg/kg p.o. dose of E. officinalis or M. koenigii has potential to reverse cognitive decline in diabetic patients.

Influence of Moderate and Severe Exercise on Memory Formation and Anxiety-like Behaviors in Male Wistar Rat

Introduction: Recent researchers have showed that regular exercise induces positive effects on cognitive functions. Exercise intensity and timing of cognitive assessment may have an interactive effect on cognitive changes. Previous researches suggest that moderate intensity treadmill running has the most consistent benefit to cognitive function. In contrast, studies find positive, negative, or null effects to cognitive function after high intensity treadmill running. The primary objective of the present study was to compare the cognitive effects of intensity treadmill running protocol 1 (Low intensity), protocol 2 (Moderate intensity) and protocol 1 plus 2 (High intensity). Materials and Methods: Male Wistar rats were divided into four groups (n=7 in each group) including: sedentary (Non-exercise), protocol 1, protocol 2, and combination of protocol 1 and 2. Step-through passive avoidance and elevated-plus maze apparatus have been used to test parameters of passive avoidance learning and anxiety-like behaviors. Results: These findings showed that combination of both protocols (Protocol 1 with protocol 2) decreased step-through latency in the passive avoidance apparatus indicating memory impairment [P 0.05] and locomotor activity %OAT [P<0.05] compared to control group but not others. Conclusion: High intensity exercise not only induced beneficial effect but also impaired memory formation.

Anticholinergic and Hypocholesterolemic Activity of Juglan regia Improves Cognitive Functions in Mice

Backgroud: Walnut appears as the Signature of the Head and the kernel looks alike as the brain. It is a traditional belief that Walnuts may be beneficial to the brain. Objective: In the light of this traditional belief, the present study was conducted to confirm the effects of Juglan regia (Walnut) on cognitive functions of mice. Method: Two doses (500, 1000 mg/kg) of Walnut kernel powder were administered along with diet for fourteen successive days to Swiss young and aged mice. 29 groups of 145 Swiss young mice and 13 groups of 65 aged mice were employed in the present study. Exteroceptive behavioral models used in the present study were elevated plus maze and passive avoidance apparatus. Results: Decreased TL and increased SDL values were indicative of a significant improvement in the memory of young and aged mice after Walnut powder administration. It also reversed the memory deficits induced by scopolamine and diazepam. In addition, the brain cholinesterase activity in young and aged mice was significantly inhibited by Walnut at the dose of 500 mg/kg. Walnut also showed a notable reduction in total cholesterol levels to the limit of 20% in young and 14% in aged mice at the dose of 500 mg/kg. Enhanced acetylcholine levels resulting from diminished AChE activity and hypocholesterolemia produced by Walnut appear to be the underlying mechanism for the improved memory of mice. Keywords: Walnut, Akhrot, Juglan regia, hypocholesterolemia, cognitive functions, brain cholinesterase.

Curcumin-Loaded BSA Nanoparticles Protect More Efficiently Than Natural Curcumin Against Scopolamine-Induced Memory Retrieval Deficit.

Introduction:There is evidence indicating that the rate of AD is lower in curry consuming populations. Then, there is an effort to elucidate if curcumin -as the main ingredient of turmeric-might affect the process of AD. However, in clinical trials of AD, a six-month curcumin treatment failed to show any progress, which might be attributable to its low bioavailability. In this line, a recent human study revealed that a more bioavailable solid lipid curcumin enhances cognition in aged adults. By the application of Bovine Serum Albumin (BSA), the current study aimed at converting curcumin to nano sizes and assessing its protective effects against scopolamine-induced passive avoidance memory retrieval deficit.Methods:Nanocurcumin was prepared via dissolution method. Male NMRI mice (20–25 g body weight) were used. The effective doses of nanocurcumin were selected according to the initial pilot test. The mice were treated with nanocurcumin 15 or 20 mg/kg/p.o or distilled water for 10 days. The animals were habituated and trained in passive avoidance apparatus on the day 10. The retention test was performed 24 hours later. Scopolamine (1 mg/kg/i.p.) or saline was injected 30 minutes before memory retention trial.Results:The findings indicated that nanocurcumin in doses 15 or 20 mg/kg/p.o prevented the retrieval deficit induced by scopolamine while natural curcumin in its equivalent doses did not have such an effect. Furthermore, nanocurcumin by itself improved memory retention comparing with the control group.Conclusion:These findings implied that the potential anti-amnesic effects of curcumin might be observed by producing and using its nanoformulation form.

Medial Prefrontal Cortical Cannabinoid CB1 Receptors Mediate Morphine–Dextromethorphan Cross State-Dependent Memory: The Involvement of BDNF/cFOS Signaling Pathways

The present study set out to assess the possible role of the medial prefrontal cortex (mPFC) cannabinoid CB1 receptors and BDNF/cFOS signaling pathways in morphine–dextromethorphan (DXM) cross state-dependent memory (SDM) using male Wistar rats. Changes on the levels of BDNF and cFOS proteins in the PFC were examined by Western blot analysis. Present results revealed that levels of BDNF and cFOS proteins were significantly increased in the animals that were trained in the passive avoidance apparatus. Intraperitoneal injection of morphine (6 mg/kg, i.p.) after training impaired memory which was associated with decreases in the levels of both proteins. Moreover, the injection of a cannabinoid CB1 receptor agonist, ACPA, or a selective CB1 receptor antagonist, AM-251, into the mPFC prior to testing had no effect on memory retrieval by itself and also on morphine-induced memory loss. Pre-test administration of DXM (a NMDA receptors antagonist, 30 mg/kg, i.p.) impaired memory retrieval and attenuated BDNF levels. Moreover, DXM administration (pre-test) prevented morphine-induced memory loss and increased the levels of both proteins, suggesting morphine-DXM cross-SDM. Interestingly, pre-test intra-mPFC injections of ACPA inhibited cross-SDM between the drugs which was associated with an elevation of BDNF expression in the PFC. Additionally, pre-test administration of an ineffective dose of DXM (10 mg/kg, i.p.) could not reverse morphine-induced memory loss, while pre-test intra-mPFC injections of AM-251 potentiated morphine-DXM cross-SDM. Taken together, it can be concluded that mPFC through CB1cannabinoid receptors has a critical role in morphine-DXM cross-SDM which may be associated with the PFC BDNF/cFOS signaling pathway.

Curcumin ameliorates scopolamine-induced mice memory retrieval deficit and restores hippocampal p-Akt and p-GSK-3β

The loss of cholinergic neurons has been a major issue in researches on Alzheimer's disease (AD) for about 40 years. Therefore, the scopolamine model of amnesia has been widely used in AD researches. Recently, it was reported that the early stage amnesia of AD is related to memory retrieval deficit. Curcumin, as the main ingredient of turmeric, has been suggested to decrease the prevalence of AD in human population. This study was conducted to assess if curcumin prevents retrieval deficit induced by scopolamine in passive avoidance task. Moreover, according to the proposed link between cholinergic system and Akt/GSK-3β (Glycogen synthase kinase 3 beta) signaling, the hippocampal contents of these proteins were determined. Male NMRI mice (20–25 g body weight) were treated with 50 or 100 mg/kg/po curcumin or its vehicle for 10 days. On day 10, the animals were trained in passive avoidance apparatus. The retention trial was performed 24 h later. Scopolamine (1 mg/kg/i.p.) or its vehicle was administered 30 min before retention test. At the completion of behavioral studies, the hippocampi were removed and western blot analysis was performed to determine hippocampal phosphorylated and total Akt and GSK-3β and beta actin contents. The results showed that curcumin treatment at 50 and 100 mg/kg doses prevented scopolamine-induced memory retrieval deficit and restored Akt and GSK dephosphorylation caused by scopolamine. Overall, these findings showed that pre-test scopolamine administration disrupts memory retrieval along with the diminished Akt and GSK-3β phosphorylation in hippocampus while curcumin administration prevented those changes.

The passive avoidance memory improving effect of curcumin in young adult mice: Considering hippocampal MMP-2, MMP-9 and Akt/GSK3β

Curcumin has been suggested as a candidate for the prevention of Alzheimer’s disease. Recently, a human study has revealed that curcumin enhances cognition in non-demented aged population. Although the neuroprotective effect of curcumin has been shown in some animal models of amnesia, no study has showed its memory improving effect in intact adult animals. This study aimed to assess the effect of curcumin on passive avoidance memory in adult young mice. Additionally, the hippocampal contents of MMP-2, MMP-9 and Akt/GSK3β were determined. Male mice weighing 20–25 g were trained in passive avoidance apparatus. Curcumin 50 or 100 mg/kg/po (according to our initial tests) or its vehicle was administered for 10 days. On day 10 the training was done and the retention trial was performed 24 h later. At the complement of behavioral studies, the hippocampal tissue was isolated and western blot analysis was performed for MMP-2, MMP-9 and Akt/GSK3β. The results indicated that curcumin improved passive avoidance memory. Moreover, it elevated hippocampal MMP-2,9 and p-Akt/t-Akt while it decreased the activated form of GSK-3β. According to these findings, it seems that curcumin improves memory and affects hippocampal MMP-2, MMP-9 and Akt/GSK3β signaling molecules in young adult animals.

Cognitive and hippocampus biochemical changes following sleep deprivation in the adult male rat

Sleep deprivation (SD) influences physiological processes such as cognitive function. The balance of oxidant and antioxidant markers, neurotrophic factors and magnesium are affected by sleep deprivation but there is no difference between pre and post training sleep deprivation. This study was designed to investigate memory retrieval and biochemical factors such as oxidant and antioxidant enzyme, brain-derived neurotrophic factor (BDNF) and magnesium levels in the hippocampus following pre and post-training sleep deprivation.Male Wistar rats (weighing 200 ± 20 g) in below groups were used: control 1, 24, 48 and 72 h SD before training groups, control2, 24 h SD1 after training (being evaluated 24 h after training) and SD2 24 after training (being evaluated 48 h after training). Memory was evaluated 90 min, 24 h or 48 h after training by step-through passive avoidance apparatus. Multiple platforms method was used to induce SD. Oxidant and antioxidant markers including glutathione (GSH), glutathione reductase (GPx), malonedialdehyde (MDA), Total antioxidant concentration, catalase, superoxide dismutase (SOD), magnesium and BDNF were assessed in the hippocampus or/and brain.72 h pre-training SD impaired short and long-term memory significantly. There was no significant difference in hippocampus oxidant and antioxidant markers compared to control. Hippocampal BDNF and magnesium did not show any changes in all SD groups.Lack of correlation between memory impairment and levels of BDNF, magnesium and/or oxidant and antioxidant balance in the hippocampus is likely to be related to animal locomotor activity in the multiple platforms method. More research is needed to clarify the role of neurochemical systems.

Scopolamine-induced passive avoidance memory retrieval deficit is accompanied with hippocampal MMP2, MMP-9 and MAPKs alteration

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by progressive loss of memory and cognitive deficit. The observed amnesia in the early stages of AD is suggested to be a retrieval problem, rather than encoding and consolidation deficit. According to the cholinergic hypothesis of AD, scopolamine is used to induce an animal model of amnesia. Howbeit the effect of scopolamine on memory retrieval is contradictory. This study aimed to assess the effect of scopolamine on passive avoidance memory retrieval. Additionally according to the reported changes of MMP-2, MMP-9 and MAPKs (ERK, P38 and JNK) in AD pathology the hippocampal contents of these proteins were determined. Male NMRI mice weighing 20–25g were trained in passive avoidance apparatus. The drug or its vehicle was injected 24h after training (30min before retention test). The hippocampal tissue was isolated and western blot analysis was done for MMP-2, MMP-9 and MAPKs (ERK, P38 and JNK). The results indicated that scopolamine (1mg/kg) disrupts passive avoidance memory retrieval. This scopolamine treatment resulted in hippocampal MMP-2 and MMP-9 decline while increased MAPKs in the hippocampus. These results suggest that cholinergic system has an important role in learnt memory retrieval. It might also suggest the positive role of MMP-2 and MMP-9 in this phase of memory while propose that MAPKs affect negatively the reactivation of memory which is compatible with MAPKs activation in AD.

Critical role of CA1 muscarinic receptors on memory acquisition deficit induced by total (TSD) and REM sleep deprivation (RSD)

AimDespite different theories regarding sleep physiological function, an overall census indicates that sleep is useful for neural plasticity which eventually strengthens cognition and brain performance. Different studies show that sleep deprivation (SD) leads to impaired learning and hippocampus dependent memory. According to some studies, cholinergic system plays an important role in sleep (particularly REM sleep), learning, memory, and its retrieval. So this study has been designed to investigate the effect of CA1 Cholinergic Muscarinic Receptors on memory acquisition deficit induced by total sleep deprivation (TSD) and REM sleep deprivation (RSD). MethodA modified water box (locomotor activity may be provide a limiting factor in this method of SD) or multiple platforms were used for induction of TSD or RSD, respectively. Inhibitory passive avoidance apparatus has been used to determine the effects of SD and its changes by physostigmine (as cholinesterase inhibitor) or scopolamine (muscarinic receptor antagonist) on memory formation. Because locomotor activity and pain perception induce critical roles in passive avoidance memory formation, we also measured these factors by open field and hot-plate instruments, respectively. ResultsThe results showed that TSD and RSD for 24 hours impaired memory formation but they did not alter locomotor activity. TSD also induced analgesia effect, but RSD did not alter it. Intra-CA1 injection of physostigmine (0.0001μg/rat) and scopolamine (0.01μg/rat) did not alter memory acquisition in the sham-TSD or sham-RSD, by themselves. Moreover, intra-CA1 injection of sub-threshold dose of physostigmine (0.0001μg/rat) and scopolamine (0.01μg/rat) could restore the memory acquisition deficit induced by RSD, while scopolamine could restore TSD-induced amnesia. Both drugs reversed analgesia induced by TSD. None of previous interventions altered locomotor activity. ConclusionAccording to this study, CA1 cholinergic muscarinic receptors play an important role in amnesia induced by both TSD and RSD. However further studies are needed for showing cellular and molecular mechanisms of surprising result of similar pharmacological effects using compounds with opposite profiles.