Radial Arm Maze Test Research Articles

NEUROPROTECTIVE EFFECT OF ABELMOSCHUS ESCULENTUS ON CHRONIC STRESS AND EVALUATION OF LOSS OF MEMORY, ADAPTOGENIC EFFECT

Objective: Objective of this study was to determine if there was any neuroprotective effect of Abelmoschus esculentus L and its role in preventing memory loss during stressful conditions. Methods: The powder of A. esculentus L. pods was extracted with methanol and was used for evaluating anti-stress activity in experimental mice groups. The five experimental mice groups, namely, control, stress control, animals treated with extract followed by exposure to stress, animals exposed to stress followed by extract treatment, and mice groups treated with diazepam was evaluated. Biomarkers included were cortisol, brain homogenate acetylcholine esterase (AchE), superoxide dismutase (SOD), and malondialdehyde (MDA). In conjugation, working memory and reference memory were also studied in all animal groups by radial arm maze test, and results were recorded as the percentage of alteration score (PAS). Results: The concentration of stress indicators such as cortisol, MDA, and AchE activity was significantly elevated in stress control animals and associated with deficit working and reference memory. However, SOD was reduced in stressed mice and increased in treatment groups compared to the control mice. The anti-stress activity of A. esculentus L. pods was significantly correlated with higher working memory and reference memory with 1.33±0.51 and 1.17±0.40 PAS in pre-stress and post-stress treated mice groups, respectively. Conclusion: Methanolic extract of A. esculentus L. pods revealed the excellent anti-stress potential and also played a significant role in enhancing both working memory and reference memory in mice.

Expression of the Transient Receptor Potential Vanilloid 1 ion channel in the supramammillary nucleus and the antidepressant effects of its antagonist AMG9810 in mice

The Transient Receptor Potential Vanilloid 1 (TRPV1) non-selective cation channel predominantly expressed in primary sensory neurons of the dorsal root and trigeminal ganglia mediates pain and neurogenic inflammation. TRPV1 mRNA and immunoreactivity were described in the central nervous system (CNS), but its precise expression pattern and function have not been clarified. Here we investigated Trpv1 mRNA expression in the mouse brain using ultrasensitive RNAScope in situ hybridization. The role of TRPV1 in anxiety, depression-like behaviors and memory functions was investigated by TRPV1-deficient mice and pharmacological antagonism by AMG9810. Trpv1 mRNA is selectively expressed in the supramammillary nucleus (SuM) co-localized with Vglut2 mRNA, but not with tyrosine hydroxylase immunopositivity demonstrating its presence in glutamatergic, but not dopaminergic neurons. TRPV1-deleted mice exhibited significantly reduced anxiety in the Light-Dark box and depression-like behaviors in the Forced Swim Test, but their performance in the Elevated Plus Maze as well as their spontaneous locomotor activity, memory and learning function in the Radial Arm Maze, Y-maze and Novel Object Recognition test were not different from WTs. AMG9810 (intraperitoneal injection 50 mg/kg) induced anti-depressant, but not anxiolytic effects. It is concluded that TRPV1 in the SuM might have functional relevance in mood regulation and TRPV1 antagonism could be a novel perspective for anti-depressant drugs.

Therapeutic Efficacy of Boric Acid Treatment on Brain Tissue and Cognitive Functions in Rats with Experimental Alzheimer's Disease.

Oxidative stress has an important role in the pathophysiology of Alzheimer's disease (AD), the most common type of dementia. Boric acid (BA) contributes significantly to the protection of the brain by reducing lipid peroxidation and supporting antioxidant defense. We aimed to evaluate the therapeutic potential of BA treatment in AD rats. Four groups were formed as Control (C), Alzheimer's (A), Alzheimer's + Boric acid (ABA), Boric acid (BA). Intracerebroventricular injection of Streptozotocin (STZ) was preferred to create an AD. After 4 weeks, BA was applied 3 times every other day. The Radial Arm Maze Test (RAMT) was used to evaluate memory and learning abilities. Biochemical and histopathological evaluations were made in the hippocampus. Initial RAMT inlet/outlet (I/O) numbers were similar. Two weeks after STZ injection, I/O numbers decreased in group A and ABA compared to group C and BA (p<0.05). After the second BA application, I/O numbers increased in the ABA group compared to the A group (p<0.05). In group A, PON-1, TOS and OSI levels were higher and TAS levels were lower than in groups BA and C. After BA treatment, PON-1 and OSI levels were lower in the ABA group than in the A group (p<0.05). Although there was an increase in TAS value and a decrease in TOS, this did not make a statistical difference. The thickness of the pyramidal cell in CA1 and the granular cell layers in the dentate gyrus, and the number of intact and degenerated neurons in the pyramidal cell layer were similar between the groups. Significant improvement in learning and memory abilities after BA application is promising for AD. These results show that BA application positively affects learning and memory abilities, and reduces oxidative stress. More extensive studies are required to evaluate histopathological efficacy.

Platycodin D stimulates AMPK activity to inhibit the neurodegeneration caused by reactive oxygen species-induced inflammation and apoptosis.

Alzheimer's disease (AD) was considered to be a neurodegenerative disease that caused cognitive impairment. Reactive Oxidative stress (ROS) was considered to be one of a major cause of the onset and progression of AD. Platycodin D (PD), a representative saponin from Platycodon grandiflorum, has conspicuous antioxidant activity. However, whether PD could protect nerve cell against oxidative injury remains unknown. This study investigated the regulatory effects of PD on neurodegeneration caused by ROS. To determine whether PD could play its own antioxidant role in neuronal protection. First, PD(2.5, 5mg/kg) ameliorated the memory impairment induced by AlCl3 (100mg/kg) combined with D-galactose (D-Gal) (200mg/kg) in mice, using the radial arm maze (RAM) test, and neuronal apoptosis in the hippocampus was evaluated by hematoxylin and eosin staining (HE). Next, the effects of PD (0.5, 1, and 2μM) on okadaic-acid (OA) (40nM) -induced apoptosis and inflammation of HT22cells were investigated. Mitochondrial ROS production was measured by fluorescence staining. The potential signaling pathways were identified through Gene Ontology enrichment analysis. The role of PD in regulating AMP-activated protein kinase (AMPK) was assessed using siRNA silencing of genes and an ROS inhibitor. In vivo, PD improved memory in mice, and recovered the morphological changes of brain tissue and nissl bodies. In vitro experiment, PD increased cell viability (p<0.01; p<0.05;p<0.001), decreased apoptosis (p<0.01), reduced excessive ROS and MDA, rised SOD and CAT content(p<0.01; p<0.05). Morover, it can block the inflammatory response caused by ROS. Be important, PD strengthen antioxidant ability by elevating AMPK activation both in vivo and in vitro. Furthermore, molecular docking suggested a good likelihood of PD-AMPK binding. AMPK activity is vital for the neuroprotective effect of PD, suggesting that PD may be a potential pharmaceutical agent to treat ROS-induced neurodegeneration.

Memory Enhancing and Neurogenesis Activity of Honey Bee Venom in the Symptoms of Amnesia: Using Rats with Amnesia-like Alzheimer's Disease as a Model.

Alzheimer's disease (AD) is mainly characterized by amnesia that affects millions of people worldwide. This study aims to explore the effectiveness capacities of bee venom (BV) for the enhancement of the memory process in a rat model with amnesia-like AD. The study protocol contains two successive phases, nootropic and therapeutic, in which two BV doses (D1; 0.25 and D2: 0.5 mg/kg i.p.) were used. In the nootropic phase, treatment groups were compared statistically with a normal group. Meanwhile, in the therapeutic phase, BV was administered to scopolamine (1mg/kg) to induce amnesia-like AD in a rat model in which therapeutic groups were compared with a positive group (donepezil; 1mg/kg i.p.). Behavioral analysis was performed after each phase by Working Memory (WM) and Long-Term Memory (LTM) assessments using radial arm maze (RAM) and passive avoidance tests (PAT). Neurogenic factors; Brain-derived neurotrophic factor (BDNF), and Doublecortin (DCX) were measured in plasma using ELISA and Immunohistochemistry analysis of hippocampal tissues, respectively. During the nootropic phase, treatment groups demonstrated a significant (P < 0.05) reduction in RAM latency times, spatial WM errors, and spatial reference errors compared with the normal group. In addition, the PA test revealed a significant (P < 0.05) enhancement of LTM after 72 hours in both treatment groups; D1 and D2. In the therapeutic phase, treatment groups reflected a significant (P < 0.05) potent enhancement in the memory process compared with the positive group; less spatial WM errors, spatial reference errors, and latency time during the RAM test, and more latency time after 72 hours in the light room. Moreover, results presented a marked increase in the plasma level of BDNF, as well as increased hippocampal DCX-positive data in the sub-granular zone within the D1 and D2 groups compared with the negative group (P < 0.05) in a dose-dependent manner. This study revealed that injecting BV enhances and increases the performance of both WM and LTM. Conclusively, BV has a potential nootropic and therapeutic activity that enhances hippocampal growth and plasticity, which in turn improves WM and LTM. Given that this research was conducted using scopolamine-induced amnesia-like AD in rats, it suggests that BV has a potential therapeutic activity for the enhancement of memory in AD patients in a dose-dependent manner but further investigations are needed.

Memory-Enhancing and Antioxidant Activities of the Hydroethanolic Leave Extract of Piliostigma reticulatum (Fabaceae) in the Monosodium Glutamate-Induced Alzheimer's Disease Model

Background: Piliostigma reticulatum (Fabaceae) is a plant used in Cameroon for the treatment of madness and migraine. Aims and Objectives: This study aims to evaluate the memory-enhancing and antioxidant activities of the hydroethanolic leaves extract of PR in the monosodium glutamate-induced Alzheimer's disease model. Materials and Methods: The Y-maze, Radial-arm maze and Novel object recognition tests were used to assess short, and long-term memory. At the end of the experiments, the brains of mice were scavenged for biochemical and histological analysis. Results: It was observed that the hydroalcoholic extract of PR leaf significantly reversed the percentage of spontaneous alternation compared to the negative control group at the different doses tested (p&lt;0.01; p&lt;0.001) in the Y-maze test. In the radial arm maze test, the extract significantly (p&lt;0.001) reduced the time spent consuming the bait, the number of reference memory and working memory errors at all doses. The treatment of animals with hydroethanolic extract of PR resulted in a significant increase in the discrimination index (p&lt;0.001) in the unfamiliar object recognition test. In addition, the extract significantly (p &lt; 0.01); p &lt; 0.001) decreased acetylcholinesterase activity,and MDA levels at all tested doses; and significantly (p &lt; 0.05; p &lt; 0.001) increased SOD level and Catalase activity in comparison to the negative control group. The histological analysis showed that the extract of Piliostigma reticulatum protected the different structures of the hippocampus against damage caused by monosodium glutamate. Conclusion : The memoryenhancing induced by the hydroethanolic leaves extract of Piliostigma reticulatum could be due to his antioxidant and anticholinesterase properties. These effects could justify the use of this plant to manage nervous system affections.

Therapeutic Treatment with Pycnogenol® Attenuates Ischemic Brain Injury in Gerbils Focusing on Cognitive Impairment, Neuronal Death, BBB Leakage and Neuroinflammation in the Hippocampus

A gerbil model of ischemia and reperfusion (IR) injury in the forebrain has been developed for studies on mechanisms, prevention and therapeutic strategies of IR injury in the forebrain. Pycnogenol® (PYC), a standardized extract of French maritime pine tree (Pinus pinaster Aiton) has been exploited as an additive for dietary supplement. In the present study, we investigated the neuroprotective effects of post-treatment with PYC and its therapeutic mechanisms in gerbils. The gerbils were given sham and IR operation and intraperitoneally injected with vehicle and Pycnogenol® (25, 50 and 100 mg/kg, respectively) immediately, at 24 hours and 48 hours after sham and IR operation. Through 8-arm radial maze test and passive avoidance test, each spatial memory and short-term memory function was assessed. To examine the neuroprotection of Pycnogenol®, we conducted cresyl violet staining, immunohistochemistry for neuronal nuclei, and Fluoro-Jade B histofluorescence. Moreover, we carried out immunohistochemistry for immunoglobulin G (IgG) to investigate blood-brain barrier (BBB) leakage and interleukin-1β (IL-1β) to examine change in pro-inflammatory cytokine. We found that IR-induced memory deficits were significantly ameliorated when 100 mg/kg Pycnogenol® was treated. In addition, treatment with 100 mg/kg Pycnogenol®, not 25 mg/kg nor 50 mg/kg, conferred neuroprotective effect against IR injury. For its mechanisms, we found that 100 mg/kg Pycnogenol® significantly reduced BBB leakage and inhibited the expression of IL-1β. Therapeutic treatment (post-treatment) with Pycnogenol® after IR effectively attenuated ischemic brain injury in gerbils. Based on these results, we suggest that PYC can be employed as an important material for ischemic drugs.

Sex-Dependent Effect of Chronic Piromelatine Treatment on Prenatal Stress-Induced Memory Deficits in Rats.

Prenatal stress impairs cognitive function in rats, while Piromelatine treatment corrects memory decline in male rats with chronic mild stress. In the present study, we aimed to evaluate the effect of chronic treatment with the melatonin analogue Piromelatine on the associative and spatial hippocampus-dependent memory of male and female offspring with a history of prenatal stress (PNS). We report that male and female young adult offspring with PNS treated with a vehicle had reduced memory responses in an object recognition test (ORT). However, the cognitive performance in the radial arm maze test (RAM) was worsened only in the male offspring. The 32-day treatment with Piromelatine (20 mg/kg, i.p.) of male and female offspring with PNS attenuated the impaired responses in the ORT task. Furthermore, the melatonin analogue corrected the disturbed spatial memory in the male offspring. While the ratio of phosphorylated and nonphosphorylated adenosine monophosphate response element binding protein (pCREB/CREB) was reduced in the two sexes with PNS and treated with a vehicle, the melatonin analogue elevated the ratio of these signaling molecules in the hippocampus of the male rats only. Our results suggest that Piromelatine exerts a beneficial effect on PNS-induced spatial memory impairment in a sex-dependent manner that might be mediated via the pCREB/CREB pathway.

Xuesaitong Combined with Dexmedetomidine Improves Cerebral Ischemia-Reperfusion Injury in Rats by Activating Keap1/Nrf2 Signaling and Mitophagy in Hippocampal Tissue.

Ischemic stroke is the most common type of cerebrovascular disease with high mortality and poor prognosis, and cerebral ischemia-reperfusion (CI/R) injury is the main murderer. Here, we attempted to explore the effects and mechanism of Xuesaitong (XST) combined with dexmedetomidine (Dex) on CI/R injury in rats. First, a rat model of CI/R injury was constructed via the middle cerebral artery occlusion (MCAO) method and treated with XST and Dex alone or in combination. Then, on the 5th and 10th days of treatment, the neurological impairment was assessed using the modified neurological severity scores (mNSS), the 8-arm radial maze test (8ARMT), novel object recognition test (NORT), and fear conditioning test (FCT). H&E staining was performed to observe the pathological changes of the hippocampus. ELISA and related kits were used to assess the monoamine neurotransmitters and antioxidant enzyme activities in the hippocampus. The ATP, mitochondrial membrane potential levels, and qRT-PCR of genes related to mitochondrial function were determined to assess mitochondrial functions in the hippocampus and western blot to determine Keap1/Nrf2 signaling pathway and mitophagy-related protein expression. The results showed that XST combined with Dex significantly reduced mNSS, improved spatial memory and learning deficits, and enhanced fear memory and cognitive memory ability in CI/R rats, which was superior to single-drug treatment. Moreover, XST combined with Dex treatment improved hippocampal histopathological damage; significantly increased the levels of monoamine neurotransmitters, neurotrophic factors, ATP, and mitochondrial membrane potential; and upregulated the activities of antioxidant enzymes and the expression of mitophagy-related proteins in the hippocampus of CI/R rats. XST combined with Dex treatment also activated the Keap1/Nrf2 signaling and upregulated the protein expression of downstream antioxidant enzymes HO-1 and NQ. Altogether, this study showed that a combination of XST and Dex could activate the Keap1/Nrf2 signaling and mitophagy to protect rats from CI/R-related neurological impairment.

Cognitive Impairments and blood-brain Barrier Damage in a Mouse Model of Chronic Cerebral Hypoperfusion

Chronic cerebral hypoperfusion (CCH) is commonly involved in various brain diseases. Tight junction proteins (TJs) are key components constituting the anatomical substrate of the blood-brain barrier (BBB). Changes in cognitive function and BBB after CCH and their relationship need further exploration. To investigate the effect of CCH on cognition and BBB, we developed a bilateral common carotid artery stenosis (BCAS) model in Tie2-GFP mice. Mice manifested cognitive impairments accompanied with increased microglia after the BCAS operation. BCAS mice also exhibited increased BBB permeability at all time points set from D1 to D42. Furthermore, BCAS mice showed reduced expression of TJs 42 d after the operation. In addition, correct entrances of mice in radial arm maze test had a moderate negative correlation with EB extravasation. Our data suggested that BCAS could lead to cognitive deficits, microglia increase and BBB dysfunction characterized by increased BBB permeability and reduced TJs expression level. BBB permeability may be involved in the cognitive impairments induced by CCH.

Neuroprotective Effects of the Ethanolic Leaf Extract of Crassocephalum crepidioides (Asteracaeae) on Diazepam-Induced Amnesia in Mice.

This study aimed to evaluate the neuroprotective effects of the ethanolic leaf extract of Crassocephalum crepidioides (Cc) on diazepam-induced amnesia in mice. Thirty mice distributed into six groups of five mice each were used. The normal control and negative control groups received 2% ethanol per os, the positive control group received piracetam (150 mg/kg, p.o), and three experimental groups were treated with three doses of ethanolic leaf extract of Cc (100, 200, and 400 mg/kg, p.o). All groups except the normal control group were co-treated with diazepam (3 mg/kg, i.p) daily for 14 days. The memory effects were evaluated using the Radial Arm Maze (RAM) and the Novel Object Recognition (NOR) tests, while the anti-depressive effects were evaluated using the tail suspension test. All animals were sacrificed at the end of the study. Hippocampi, isolated from the right hemisphere, were used to prepare a homogenate for the determination of oxidative stress biomarkers. The ethanolic leaf extract of cc significantly (p < 0.001) decreased the number of working and reference memory errors in the RAM test and induced a significant (p < 0.01) increase in the time spent exploring the novel object in the NOR test. The extract also induced a significant (p < 0.001) increase in the mobility time in tail suspension. Moreover, compared to the negative control group, the extract significantly (p < 0.01) increased superoxide dismutase activity and significantly (p < 0.01) decreased malondialdehyde levels. The histopathological analysis of hippocampi showed that the cc extract increased cell density when compared with the negative control. These results suggest that the ethanolic left extract of cc could have neuroprotective properties, which could be attributed to its antioxidant properties.

Memory-enhancing, Antioxidant, and Anticholinesterase Effects of Inhaled Achillea pseudoaleppica Essential Oil on Scopolamine-induced Amnesic Rats

Achillea species are used for therapeutic purposes in many countries. This study demonstrated the memory-enhancing, antioxidant, and anticholinesterase effects of Achillea pseudoaleppica essential oil in scopolamine-induced amnesia. The GC/FID-GC/MS system revealed camphor as the major compound in the oil. The application of the essential oil (1% and 3%) was performed on the rats by inhalation for 21 consecutive days before the performance of the behavioral tests (Y-maze and radial-arm maze tests). The essential oil application increased the spontaneous alternation behavior in scopolamine-induced rats in the Y-maze task. Furthermore, essential oil administration decreased working memory errors and reference memory errors in scopolamine-treated rats in the radial-arm maze test. Therefore, Achillea pseudoaleppica essential oil inhalation improved memory in scopolamine-treated rats. In addition, acetylcholinesterase and antioxidant profiles of the hippocampal tissues of the rats were examined. Essential oil administration decreased acetylcholinesterase and superoxide dismutase specific activities and malondialdehyde levels while increasing the total content of reduced glutathione in the rat hippocampus in scopolamine-treated rats. Therefore, in this study, the combination of scopolamine and Achillea pseudoaleppica essential oil improved memory formation and increased the activities of antioxidants and anticholinesterase.

Phytochemical and Pharmacological Screening of Salvia Hispanica Seed Extracts against Alzeimer’s Disease in Rodents

The objective of this study was to identify the potential of salvia hispanica as protective and therapeutic agent against Alzheimer’s disease. The learning and memory enhancing activity of saliva hispanica seed extract were investigated in rats by using the ethanol induced cognitive impairment and diazepam induced amnesia and its effects on learning and memory were examined by using Morris water maze (MWM) test and 8-radial arm maze (8-RAM) test. For Morris water maze test all groups showed significantly (P value is &lt; 0.01 &amp;&lt; 0.05) decreases transfer latency time at all periods as compared to ethanol and diazepam inducing group &amp; for radial arm maze test all groups showed significantly (P value is&lt; 0.0001) decreased in the time taken to reach the paired arm and number of entries in baited arm and non-baited arm as compared to ethanol inducing group. Therefore seed extracts of salvia hispanica exhibited significantly learning and memory activity in Alzheimer’s disease.

Phytochemical Screening and Learning and Memory Activity of Cucurbita pepo against Ethanol Induced Cognitive Impairment in Rodents by Using 8-ARM Radial Maze [8-ARM

The present study was undertaken to investigate the learning and memory enhancing activity of Cucurbita pepo seed extract in rats by using the ethanol induced cognitive impairment and its effects were examined by using 8-radial arm maze (8-RAM) test. For radial arm maze test all groups showed significantly (P value is&lt; 0.0001&amp; &lt; 0.001) decreased in the time taken to reach the paired arm and number of entries in baited arm and non-baited arm as compared to ethanol inducing group. Therefore seed extracts of Cucurbita pepo exhibited significantly learning and memory activity in Alzheimer’s disease.

Sulforaphane Attenuates Chronic Intermittent Hypoxia-Induced Brain Damage in Mice via Augmenting Nrf2 Nuclear Translocation and Autophagy.

Obstructive sleep apnea–hypopnea syndrome (OSAHS), typically characterized by chronic intermittent hypoxia (CIH), is associated with neurocognitive dysfunction in children. Sulforaphane (SFN), an activator of nuclear factor E2-related factor 2 (Nrf2), has been demonstrated to protect against oxidative stress in various diseases. However, the effect of SFN on OSAHS remains elusive. In this research, we investigated the neuroprotective role of SFN in CIH-induced cognitive dysfunction and underlying mechanisms of regulation of Nrf2 signaling pathway and autophagy. CIH exposures for 4 weeks in mice, modeling OSAHS, contributed to neurocognitive dysfunction, manifested as increased working memory errors (WMEs), reference memory errors (RMEs) and total memory errors (TEs) in the 8-arm radial maze test. The mice were intraperitoneally injected with SFN (0.5 mg/kg) 30 min before CIH exposure everyday. SFN treatment ameliorated neurocognitive dysfunction in CIH mice, which demonstrates less RME, WME, and TE. Also, SFN effectively alleviated apoptosis of hippocampal neurons following CIH by decreased TUNEL-positive cells, downregulated cleaved PARP, cleaved caspase 3, and upregulated Bcl-2. SFN protects hippocampal tissue from CIH-induced oxidative stress as evidenced by elevated superoxide dismutase (SOD) activities and reduced malondialdehyde (MDA). In addition, we found that SFN enhanced Nrf2 nuclear translocation to hold an antioxidative function on CIH-induced neuronal apoptosis in hippocampus. Meanwhile, SFN promoted autophagy activation, as shown by increased Beclin1, ATG5, and LC3II/LC3I. Overall, our findings indicated that SFN reduced the apoptosis of hippocampal neurons through antioxidant effect of Nrf2 and autophagy in CIH-induced brain damage, which highlights the potential of SFN as a novel therapy for OSAHS-related neurocognitive dysfunction.

Effects of Wolf Spiders' Captive Environment on Their Locomotor and Exploratory Behaviours.

Simple SummarySince the 1960s, abuses of domestic and of wild animals that have been tamed or are held in captivity have been legally prohibited and laws ensure their well-being. Many scientific investigations carried out in this context recommend ways to adapt farming and thus to avoid physical and/or psychological suffering. Evaluations of animals’ welfare in captivity entail the need to understand in detail the fundamental behaviours of the focus species and to know the degree of their variation to be able to establish objective bases that can ensure breeding conditions that respect the animals’ welfare. Current laws do not apply to invertebrate animals (such as insects or spiders) and consideration of the welfare of these animals in captivity is neglected. Here, I compared the behaviour of wild adult spiders just after collection and that of adult spiders hatched and bred in the laboratory. My results show that captivity induced rapid changes of wild spiders’ behaviour once in captivity. Therefore, it is important to establish the best breeding conditions for the needs of both invertebrate and vertebrate animals in order to promote their well-being.Here I detail the effects of the abiotic/captive environment of an adult wandering spider, Pardosa saltans (Lycosidae) on its behaviour. These studies focused on spiders collected as adults in their natural environment and spiders developed in the laboratory under controlled conditions. Wild-caught spiders were tested either immediately after capture or after being housed for 15 days post-collection. Laboratory reared spiders were kept in different environments: small or large space combined with the presence or absence of litter. Two tests evaluated by sex show the influence of these rearing conditions: an open-field test and a radial-arm maze test. The results show that wild caught spiders of both sexes tested immediately after capture weighed significantly less and were significantly more active than spiders housed in the laboratory for 15 days and spiders reared in the laboratory. Laboratory conditions induced a positive impact on body mass and negative impact on behaviour activities. The locomotor and exploratory activities of spiders of both sexes kept in container without substrate showed lower. My results suggest that the physical enrichment of the environment can reduce these negative effects for females, but not for males that seem to be more affected by being reared under controlled conditions.

Therapeutic effects of stiripentol against ischemia-reperfusion injury in gerbils focusing on cognitive deficit, neuronal death, astrocyte damage and blood brain barrier leakage in the hippocampus.

Stiripentol is an anti-epileptic drug for the treating of refractory status epilepticus. It has been reported that stiripentol can attenuate seizure severity and reduce seizure-induced neuronal damage in animal models of epilepsy. The objective of the present study was to investigate effects of post-treatment with stiripentol on cognitive deficit and neuronal damage in the cornu ammonis 1 (CA1) region of the hippocampus proper following transient ischemia in the forebrain of gerbils. To evaluate ischemia-induced cognitive impairments, passive avoidance test and 8-arm radial maze test were performed. It was found that post-treatment with stiripentol at 20 mg/kg, but not 10 or 15 mg/kg, reduced ischemia-induced memory impairment. Transient ischemia-induced neuronal death in the CA1 region was also significantly attenuated only by 20 mg/kg stiripentol treatment after transient ischemia. In addition, 20 mg/kg stiripentol treatment significantly decreased ischemia-induced astrocyte damage and immunoglobulin G leakage. In brief, stiripentol treatment after transient ischemia ameliorated transient ischemia-induced cognitive impairment in gerbils, showing that pyramidal neurons were protected and astrocyte damage and blood brain barrier leakage were significantly attenuated in the hippocampus. Results of this study suggest stiripentol can be developed as a candidate of therapeutic drug for ischemic stroke.

SiRNA Mediated GSK3β Knockdown Targets Insulin Signaling Pathway and Rescues Alzheimer's Disease Pathology: Evidence from In Vitro and In Vivo Studies.

Sporadic Alzheimer's disease (sAD) is a progressive neurodegenerative disorder with dysfunctional insulin signaling and energy metabolism. Emerging evidence suggests impairments in brain insulin responsiveness, glucose utilization, and energy metabolism may be major causes of amyloid precursor protein mishandling. The support for this notion comes from the studies wherein streptozotocin (STZ) induced brain insulin resistance in rodent model resulted in sAD-like neuropathology with cognitive decline. Our previous study showed a compromised insulin signaling pathway, glucose uptake, glucose metabolism, and energy homeostasis in STZ-induced glial-neuronal coculture and in vivo model of sAD. Various components of insulin signaling pathway were examined to understand the metabolic correlation, and GSK3β was selected for gene knockdown strategy to reverse sAD pathology based on the data. In the present study, we have synthesized carboxylated graphene oxide (GO) nanosheets functionalized with PEG and subsequently with polyethylenimine (PEI) to provide attachment sites for GSK3β siRNA. Our results showed that siRNA mediated knockdown of the GSK3β gene reduced expression of amyloid pathway genes (APP and BACE1), which was further confirmed by reduced amyloid beta (Aβ) levels in the in vitro STZ-induced sAD model. GSK3β knockdown also restored insulin signaling, AMPK and Mapk3 pathway by restoring the expression of corresponding candidate genes in these pathways (IR, Glut1/3, Prkaa1/2, Mapk3, BDNF) that reflected improved cellular energy homeostasis, neuronal proliferation, differentiation, maturation, and repair. Behavioral data from Morris water maze (MWM), open field (OF), novel object recognition (NOR), Y maze, and radial arm maze (RAM) tests showed that 0.5 μg nanoformulation (GOc-PP-siRNAGSK3β) intranasally for 7 days improved spatial memory, rescued anxiety like behavior, improved visual and working memory, and rescued exploratory behavior in STZ-induced sAD rats. GSK3β silencing resulted in decreased BACE1 expression and prevented accumulation of Aβ in the cortex and hippocampus. These molecular findings with improved behavioral performances were further correlated with reduced amyloid beta (Aβ) and neurofibrillary tangle (NFTs) formation in the cortex and hippocampus of GOc-PP-siRNAGSK3β administered sAD rats. Therefore, it is conceivable from the present study that nanoparticle-mediated targeting of GSK3β in the sAD appears to be a promising strategy to reverse sAD pathology.

Neuropeptide-S affects cognitive impairment and depression-like behavior on MPTP induced experimental mouse model of Parkinson’s disease

The present study proposes to investigate the effect of neuropeptide–S (NPS) on cognitive functions and depression-like behavior of MPTP-induced experimental model of Parkinson’s disease (PD). Three-month-old C57BL/6 mice were randomly divided into three groups as; Control, Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and MPTP + NPS 0.1 nmol (received intraperitoneal injection of MPTP and intracerebroventricular injection of NPS, 0.1 nmol for seven days). The radial arm maze and pole tests were carried out, and the levels of tyrosine hydroxylase (TH) were determined using western blotting. A mass spectrometer was used to measure the levels of dopamine, glutamic acid, and glutamine. The T-turn and time to descend enhanced in MPTP group, while these parameters were decreased by NPS treatment. In the MPTP group, the number of working memory errors (WME) and reference memory errors (RME) increased, whereas NPS administration decreased both parameters. Sucrose preference decreased in the MPTP group while increasing in the NPS group. MPTP injection significantly reduced dopamine, glutamic acid, and glutamine levels. NPS treatment restored the MPTP-induced reduction in glutamine and glutamic acid levels. NPS may be involved in the future treatment of cognitive impairments and depression-like behaviors in PD.

Blockade of adenosine A2A receptor alleviates cognitive dysfunction after chronic exposure to intermittent hypoxia in mice

Obstructive sleep apnea-hypopnea syndrome (OSAHS) is widely known for its multiple systems damage, especially neurocognitive deficits in children. Since their discovery, adenosine A2A receptors (A2ARs) have been considered as key elements in signaling pathways mediating neurodegenerative diseases such as Huntington's and Alzheimer's, as well as cognitive function regulation. Herein, we investigated A2AR role in cognitive impairment induced by chronic intermittent hypoxia (CIH). Mice were exposed to CIH 7 h every day for 4 weeks, and intraperitoneally injected with A2AR agonist CGS21680 or A2AR antagonist SCH58261 half an hour before IH exposure daily. The 8-arm radial arm maze was utilized to assess spatial memory after CIH exposures.To validate findings using pharmacology, the impact of intermittent hypoxia was investigated in A2AR knockout mice. CIH-induced memory dysfunction was manifested by increased error rates in the radial arm maze test. The behavioral changes were associated with hippocampal pathology, neuronal apoptosis, and synaptic plasticity impairment. The stimulation of adenosine A2AR exacerbated memory impairment with more serious neuropathological damage, attenuated long-term potentiation (LTP), syntaxin down-regulation, and increased BDNF protein. Moreover, apoptosis-promoting protein cleaved caspase-3 was upregulated while anti-apoptotic protein Bcl-2 was downregulated. Consistent with these findings, A2AR inhibition with SCH58261 and A2AR deletion exhibited the opposite result. Overall, these findings suggest that A2AR plays a critical role in CIH-induced impairment of learning and memory by accelerating hippocampal neuronal apoptosis and reducing synaptic plasticity. Blockade of adenosine A2A receptor alleviates cognitive dysfunction after chronic exposure to intermittent hypoxia in mice.