Induced Memory Impairment Research Articles

Concomitant administration of resveratrol and resistance training ameliorates acrylamide-induced spatial learning impairment in rats.

The present study examined effects of resistance training (RT) and resveratrol (RES) alone and together on acrylamide (AC)-induced memory impairment in rats. Animals were divided into 6 groups: (1) Control group which received normal saline intraperitoneally (ip) daily for 8 weeks; (2) Scopolamine (SCO) group which received SCO (1 mg/kg/day, ip) for 8 weeks; (3) AC group which received AC (5 mg/kg/day, ip) for 8 weeks; (4) AC + RT group which received AC (5 mg/kg/day, ip) for 8 weeks and performed RT (5 days a week for 8 weeks); (5) AC + RES group which received AC (5 mg/kg/day, ip) and RES (1 mg/kg/day, ip) for 8 weeks; and (6) AC + RT + RES group which received AC (5 mg/kg/day, ip) and RES (1 mg/kg/day, ip) for 8 weeks and performed RT (5 days a week for 8 weeks). On day 53, animal training began in the Morris Water Maze (MWM) and 24 hr after the last training, the probe test was performed. RT and RES alone did not significantly affect escape latency or traveled distance increased by AC. However, concomitant RES and RT treatment significantly reduced these parameters compared to the AC group. Co-treatment with RES and RT also significantly increased the time spent in the target quadrant compared to the AC group. Lipid peroxidation was reduced in the AC+RES and AC+RT+RES groups compared to the AC group. It seems that daily co-treatment with RES and RT for 8 weeks ameliorates the memory-impairing effects of AC.

Preclinical Assessment of <i>Crocus sativus</i> Extract Loaded Nano Emulsion for Scopolamine Induced Cognitive Impairment: A Comprehensive Safety and Efficacy Study

Background 
 Crocus sativus is popular herb used to improve and treat the memory, cognition related functions of brain and thereby impose significant role in improve and maintain brain health. The medicinal important part of Crocus sativus is stigma of flower which is rich in apocarotenoids crocin, picrocrocin, safranal and many more volatile compounds. The pharmacological actions such as antioxidant, anti-amyloidogenic, anti-depressant, anti depressant, anti cancer, anti inflammatory etc. properties are attributed due to of presence of caratenoids. However the poor stability, solubility and enzymatic degradation of bioactives of Crocus sativus have substantially limited their therapeutic application. In this study, a saffron nano emulsion of carotenoid rich fraction of Crocus sativus extract was assessed for its safety and efficacy.
 Methodology
 The single dose acute oral toxicity assessment of nanoemulsion was performed as per OECD 420 to determine the lethal dose (LD50). The subacute repeated 28 days oral toxicity was performed to provide the effective dose for the preclinical assessment as per OECD guideline 407 The animals were observed during the entire toxicity experimentation for any toxic signs and changes of hematological, biochemistry parameters. The efficacy study of saffron nano emulsion was evaluated by two behavioral test models- Passive avoidance test and Morris water maze test using scopolamine induced memory impairment.
 Results & Conclusions
 Animals administered 500 mg/kg/day as single dose orally did not cause any signs of toxicity or mortality in rats and results of acute toxicity assessment of saffron nano emulsion has indicated that the NOAEL (No Observed Adverse Effective Level) of saffron nano emulsion was found to be 500 mg/kg. In subacute toxicity study three different dose of 75, 100 & 125 mg/kg/day for 28 days administered orally in animals revealed no significant changes in body weight, hematological, biochemical parameters. The histopathological study has indicated no pathological changes observed in the vital organs of rats treated with the 125 mg/kg/day.
 The efficacy assessment of saffron nano emulsion using two behavioral models have suggested that nano emulsion at the dose of 10 mg/kg/day was significantly reduced the Scopolamine induced memory impairment.

HDAC9-mediated calmodulin deacetylation induces memory impairment in Alzheimer's disease.

Alzheimer's disease (AD) is a neurodegenerative disease characterized by progressive cognitive dysfunction and memory impairment. AD pathology involves protein acetylation. Previous studies have mainly focused on histone acetylation in AD, however, the roles of nonhistone acetylation in AD are less explored. The protein acetylation and expression levels were detected by western blotting and co-immunoprecipitation. The stoichiometry of acetylation was measured by home-made and site-specific antibodies against acetylated-CaM (Ac-CaM) at K22, K95, and K116. Hippocampus-dependent learning and memory were evaluated by using the Morris water maze, novel object recognition, and contextual fear conditioning tests. We showed that calmodulin (CaM) acetylation is reduced in plasma of AD patients and mice. CaM acetylation and its target Ca2+ /CaM-dependent kinase II α (CaMKIIα) activity were severely impaired in AD mouse brain. The stoichiometry showed that Ac-K22, K95-CaM acetylation were decreased in AD patients and mice. Moreover, we screened and identified that lysine deacetylase 9 (HDAC9) was the main deacetylase for CaM. In addition, HDAC9 inhibition increased CaM acetylation and CaMKIIα activity, and hippocampus-dependent memory in AD mice. HDAC9-mediated CaM deacetylation induces memory impairment in AD, HDAC9, or CaM acetylation may become potential therapeutic targets for AD.

Environmental enrichment improves social isolation-induced memory impairment: The possible role of ITSN1-Reelin-AMPA receptor signaling pathway.

Environmental enrichment (EE) through combination of social and non-biological stimuli enhances activity-dependent synaptic plasticity and improves behavioural performance. Our earlier studies have suggested that EE resilience the stress induced depression/ anxiety-like behaviour in Indian field mice Mus booduga. This study was designed to test whether EE reverses the social isolation (SI) induced effect and improve memory. Field-caught mice M. booduga were subjected to behaviour test (Direct wild, DW), remaining animals were housed under SI for ten days and then housed for short-term at standard condition (STSC)/ long-term at standard condition (LTSC) or as group in EE cage. Subsequently, we have examined reference, working memory and expression of genes associated with synaptic plasticity. Our analysis have shown that EE reversed SI induced impairment in reference, working memory and other accompanied changes i.e. increased level of Intersectin 1 (ITSN1), Huntingtin (Htt), Synaptotagmin -IV (SYT4), variants of brain-derived neurotrophic factor (Bdnf - III), α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor (GluR1) expression, and decreased variants of Bdnf (IV), BDNF, Reelin, Apolipoprotein E receptor 2 (ApoER2), very low-density lipoprotein receptor (VLDLR), Src family tyrosine kinase (SFKs), Disabled protein (Dab)-1, Protein kinase B (PKB/Akt), GluR2, Mitogen-activated protein kinase (MAPK) and Extracellular signal-regulated kinase (ERK1/2) expression. In addition, SI induced reduction in BDNF expressing neurons in dentate gyrus of hippocampus reversed by EE. Further, we found that SI decreases small neuro-active molecules such as Benzenedicarboxylic acid, and increases 2-Pregnene in the hippocampus and feces reversed by EE. Overall, this study demonstrated that EE is effectively reversed the SI induced memory impairment by potentially regulating the molecules associated with the ITSN1-Reelin-AMPA receptor pathway to increase synaptic plasticity.

Single-Cell Transcriptome Reveals Cell Type–Specific Molecular Pathology in a 2VO Cerebral Ischemic Mouse Model

Post-ischemia memory impairment is a major sequela in cerebral ischemia patients. However, cell type–specific molecular pathology in the hippocampus after ischemia is poorly understood. In this study, we adopted a mouse two-vessel occlusion ischemia model (2VO model) to mimic cerebral ischemia–induced memory impairment and investigated the single-cell transcriptome in the hippocampi in 2VO mice. A total of 27,069 cells were corresponding 14 cell types with neuronal, glial, and vascular lineages. We next analyzed cell-specific gene alterations in 2VO mice and the function of these cell-specific genes. Differential expression analysis identified cell type–specific genes with altered expression in neurons, astrocytes, microglia, and oligodendrocytes in 2VO mice. Notably, four subtypes of oligodendrocyte precursor cells with distinct differentiation pathways were suggested. Taken together, this is the first single-cell transcriptome analysis of gene expression in a 2VO model. Furthermore, we suggested new types of oligodendrocyte precursor cells with angiogenesis and neuroprotective potential, which might offer opportunities to identify new avenues of research and novel targets for ischemia treatment.

Evaluation of Anti Alzheimer Activity of Ethanolic Extract of Aerial Parts of Justicia tranquebariensis L.F Against Scopalamine Induced Memory Impairment in Swiss Albino Mice

Evaluation of Anti Alzheimer Activity of Ethanolic Extract of Aerial Parts of Justicia tranquebariensis L.F Against Scopalamine Induced Memory Impairment in Swiss Albino Mice

The Neuroprotective Effects of Dendropanax morbifera Water Extract on Scopolamine-Induced Memory Impairment in Mice.

This study investigated the neuroprotective effects of Dendropanax morbifera leaves and stems (DMLS) water extract on scopolamine (SCO)-induced memory impairment in mice. First, we conducted experiments to determine the protective effect of DMLS on neuronal cells. Treatment with DMLS showed a significant protective effect against neurotoxicity induced by Aβ(25-35) or H2O2. After confirming the neuroprotective effects of DMLS, we conducted animal studies. We administered DMLS orally at concentrations of 125, 250, and 375 mg/kg for 3 weeks. In the Y-maze test, SCO decreased spontaneous alternation, but treatment with DMLS or donepezil increased spontaneous alternation. In the Morris water-maze test, the SCO-treated group showed increased platform reach time and decreased swim time on the target platform. The passive avoidance task found that DMLS ingestion increased the recognition index in short-term memory. Furthermore, memory impairment induced by SCO reduced the ability to recognize novel objects. In the Novel Object Recognition test, recognition improved with DMLS or donepezil treatment. In the mouse brain, except for the cerebellum, acetylcholinesterase activity increased in the SCO group and decreased in the DMLS and donepezil groups. We measured catalase and malondialdehyde, which are indicators of antioxidant effectiveness, and found that oxidative stress increased with SCO but was mitigated by DMLS or donepezil treatment. Thus, our findings suggest that ingestion of DMLS restored memory impairment by protecting neuronal cells from Aβ(25-35) or H2O2-induced neurotoxicity, and by reducing oxidative stress.

The Unfolded Protein Response in a Murine Model of Alzheimer's Disease: Looking for Predictors.

Alzheimer's disease (AD) represents the most frequent type of dementia worldwide, and aging is the most important risk factor for the sporadic form of the pathology. The endoplasmic reticulum (ER), the main cellular actor involved in proteostasis, appears significantly compromised in AD due to the accumulation of the β-amyloid (Aβ) protein and the phosphorylated Tau protein. Increasing protein misfolding activates a specific cellular response known as Unfolded Protein Response (UPR), which orchestrates the recovery of ER function. The aim of the present study was to investigate the role of UPR in a murine model of AD induced by intracerebroventricular (i.c.v.) injection of Aβ1-42 oligomers at 3 or 18 months. The oligomer injection in aged animals induced memory impairment, oxidative stress, and the depletion of glutathione reserve. Furthermore, the RNA sequencing and the bioinformatic analysis performed showed the enrichment of several pathways involved in neurodegeneration and protein regulations. The analysis highlighted the significant dysregulation of the protein kinase RNA-like ER kinase (PERK), inositol-requiring protein 1α (IRE1α) and activating transcription factor 6 (ATF-6). In turn, ER stress affected the PI3K/Akt/Gsk3β and MAPK/ERK pathways, highlighting Mapkapk5 as a potential marker, whose regulation could lead to the definition of new pharmacological and neuroprotective strategies to counteract AD.

Protective effects of alpha-lipoic acid on anxiety-like behavior, memory and prevention of hippocampal oxidative stress in methamphetamine-treated rats.

Alpha-lipoic acid is an essential cofactor for aerobic metabolism and acts as a potent antioxidant in the body. It has been shown that acute exposure to methamphetamine induces oxidative stress, which is responsible for severe cognitive deficits in animals. The hippocampus plays a crucial role in the processing of memory and anxiety-like behavior. In this study, preventive effect of the alpha-lipoic acid on memory impairment in methamphetamine-induced neurotoxicity was investigated. Wistar male rats (200-220g) were allocated to five groups (seven rats in each group): (1) saline + saline, (2) saline + vehicle (sunflower oil as alpha-lipoic acid solvent), (3) methamphetamine + vehicle, (4) methamphetamine + alpha-lipoic acid 10mg/kg, and (5) methamphetamine + alpha-lipoic acid 40mg/kg. Rats received intraperitoneal methamphetamine repeatedly (2 × 20mg/kg, 2h interval). Alpha-lipoic acid was injected 30min, 24h, and 48h after the last injection of methamphetamine. The passive avoidance test and open field were used for evaluation of memory retrieval and anxiety, respectively. After behavioral test, rats were anesthetized, their brains were extracted, and after preparing hippocampal homogenates, malondialdehyde (MDA) level, catalase, and superoxide dismutase (SOD) activities were evaluated. Statistical analysis showed that injection of saline or sunflower oil had no significant effect on anxiety, memory, or oxidative stress markers. Methamphetamine induced memory impairment, increased anxiety-like behavior and MDA level, but it reduced catalase and SOD activity. Treatment with alpha-lipoic acid decreased MDA, increased catalase and SOD activity, and also prevented memory impairment and anxiety-like behavior. Our results showed that alpha-lipoic acid protected the hippocampus from oxidative stress by elevating SOD and CAT activities and reduced memory impairment following acute methamphetamine injection. These findings suggest that alpha-lipoic acid may have a protective effect against the adverse effects of methamphetamine exposure on the hippocampus. Therefore, the current data indicated that ALA can reduce oxidative stress predominantly by its antioxidant property.

Acute single non-sedative doses of NOP receptor agonists affect acquisition of object location memory but repeated high doses do not induce long-lasting deficits

The Nociceptin/Orphanin FQ (N/OFQ) system has been shown to modulate various aspects of long-term memory. It is therefore important to study the effects on memory impairment by nociceptin receptor (NOP) agonists under preclinical development. In the present study, we investigated the effect of systemic injection of two small molecule selective NOP agonists, AT-202 and AT-524, in the object location memory task in male and female mice. Since high doses of NOP agonists have been shown to induce sedation, we first determined the sedative doses for the two compounds and found them to be higher in female than in male mice. We then observed that sub-sedative doses of NOP agonists administered before learning, induced memory impairment during a test session performed 24 h later. Again, female mice were less sensitive to the amnesic effects than males. On the contrary, in male mice, NOP agonists did not produce amnesia when they were injected after learning, suggesting that they do not affect the consolidation of object location memory. Finally, repeated administration of high doses of NOP agonists over 7 days did not impair long-term spatial memory. Together, our data show for the first time that NOP receptor agonists impair the acquisition of object location memory with sex-dependent potency but do not affect memory consolidation, and that repeated stimulation of the receptor does not compromise long-term episodic-like spatial memory.

Evaluation of neuroprotective and anti-amnesic effects of the chloroform fraction of Nigella sativa L. on scopolamine-induced memory impairment in rats

The aim of this study was to investigate the neuroprotective and anti-amnesic effects of total extract (NTE) and chloroform fraction of Nigella sativa (NCE) on scopolamine (SCO)-induced memory impairment in the rat. After plant extraction and fractionation, the rats were treated with different doses of NTE (200, 400, and 800 mg/kg) and NCE (50, 100 or 200 mg/kg) before scopolamine administration for 7 successive days compared to donepezil (DON). Learning power and memory capacity of the treated animals were evaluated and the rat brain samples were further assessed for in vivo acetylcholinesterase (AChE) activity, lipid peroxidation, and finally validated by histopathological examination. Pretreatment with NTE and NCE effectively increased antioxidant activity, decreased cholinesterase activity and malondialdehyde (MDA) content in the hippocampal and cortical tissues as well as mitigated scopolamine-induced behavioral, and histological changes in a manner comparable to DON. Based on the pathology results, the most toxicity of NCE was observed at 200 mg/kg. The observed neuroprotective and anti-amnesic effects of NCE indicate that this fraction could be a promising candidate both for further studies to isolate the active components and for use in clinical trials in patients with cognitive impairment.

Cholinergic cognitive enhancer effect of Salvia triloba L. essential oil inhalation in rats

Objective: Current treatment of Alzheimer’s disease is provided by cholinesterase inhibitors. Salvia triloba L. (syn. Salvia fruticosa Mill.),
 a species mostly consumed as refreshing herbal tea in traditional medicine, is rich in 1,8-cineole that is known to have cholinesterase
 inhibiting effects. In this study, we investigated cognitive enhancer effects of S. triloba essential oil inhalation on healthy control rats
 and rats with scopolamine induced memory impairment.
 Materials and Methods: S. triloba samples from different geographical locations of Turkey were hydro-distilled and analyzed by Gas
 Chromatography-Mass Spectrometry (GC-MS). The optimum sample with the highest 1,8-cineole and lowest camphor, α-thujone and
 β-thujone content was selected. In vitro cholinergic and antioxidant potentials of the selected essential oil were calculated. Cognitive
 enhancer and anti-amnestic effects of the inhaled essential oil on rats were assessed by means of Morris water maze. The bioavailability
 of 1,8-cineole in blood of rats was measured by GC-MS.
 Results: The group that inhaled S. triloba significantly outperformed control group, namely faster achieving peak escape latency
 performance in Morris water maze. However, S. triloba inhalation failed to restore scopolamine induced learning impairment.
 Conclusion: In this study, we report positive effects of inhaling S. triloba essential oil as a complementary treatment for supporting
 cognitive functions.

Neuroprotective Potential of Vitamin B-12 Against Cadmium–Induced Neuroinflammation Mediated Memory Dysfunctions in Adult Albino Mice

Cadmium induces neurotoxicity in brain and results in increased enzymatic functions, accumulation of Amyloid beta plaque and Neuo Fibrillary Tangles (NFTs) causing neurodegenerative diseases. The purpose of the present work was to investigate the anti-inflammatory or anti-oxidative potential of vitaminB12 against Cd -induced memory impairment and mechanism of signaling pathway of vitamin-B12 protection in Cd-induced neuroinflammatory in mice model. Male albino mice of BALB/C trait of age 7 to 8 weeks and weighing about (30-32±3g) were used as model animal in the study. All mice were divided in three groups. Control Group (CG) treated with 0.9% saline (1mL/Kg), Cd Cl2 administered Group (CD) (1mg/kg) and Cd +Vitamin administered group (CV) B-12 (500µg/kg). CD group was treated with Cd Cl2 for three weeks on alternate days while CV group was treated with Vitamin B12 and toxin CdCl2 for the next two weeks intraperitonealy. Behavior tests like Morris Water Maze (MWM) and Y-Maze (YM) tests were conducted on the experimental mice to study the neuro protective potential of Vitamin-B12 against CdCl2 induced memory dysfunctions. After completing the above procedures, mice were sacrificed and the brains of each group were collected for protein quantification step and western blotting. The Immuno blots of Iba-1, NF-kB, TNF-α, IL-1β, BACE1 and Aβ proteins in the brain homogenates of CD and CV mice confirm the anti-neuroinflammatory potential of vitamin-B12 against Cadmium –induced Neuroinflammation. Escape latency of CV group mice receiving Methylcobalamine was less and showed better performance in MWM test. The results of Y-maze test also showed that the spontaneous percentage alternation of CD group mice was less than CV and CG group of mice. Immuno blot of p-Akt confirm the signaling pathways of vitamin-B12 protection in Cd-induced neuroinflammatory mediated memory-impairment in the model mice. Our findings suggest that Vitamin-B12 could be a potent candidate drug for treating cognitive dysfunctions due to its anti-inflammatory and anti-oxidative potential. Our study also shows that Vitamin-B12 activates p-Akt signaling pathway along with decreasing the NF-Κb, TNF-α and IL-1β to protect the brain of mice against CdCl2 neurotoxicity.

Effects and mechanism of extracts rich in phenylpropanoids-polyacetylenes and polysaccharides from Codonopsis Radix on improving scopolamine-induced memory impairment of mice

Ethnopharmacological relevanceAlzheimer's disease (AD) is a progressive developmental neurodegenerative disease that primarily develops in old age. Memory impairment is an important manifestation of AD. It has been demonstrated that inflammation and oxidative stress are important mediators in the development and progression of AD. Codonopsis Radix (CR) has a long history of consumption, exhibiting lots of beneficial health effects, including anti-ageing, antioxidant, and anti-inflammatory properties. However, studies on the effects of CR on scopolamine-induced amnesia have rarely been reported. Aim of the studyThe aim of this study was to investigate the ameliorative effect of macromolecular portion (polysaccharides, POL) and small molecule portion (fine extract rich in phenylpropanoids-polyacetylenes, EPP) from CR on improving scopolamine-induced memory impairment and to elucidate the potential mechanism of action. Materials and methodsC57BL/6 mice were pretreated with EPP (0.2, 0.4, and 0.6 g/kg), POL (0.3, 0.6, and 0.9 g/kg), and donepezil (5 mg/kg) by gavage for 7 days, followed by intraperitoneal injection of scopolamine (1 mg/kg) to induce memory impairment. The 16S rRNA gene sequencing, histopathological, western blotting, and biochemical analysis (various biochemical markers and protein expressions related to cholinergic system, oxidative stress, and neuroinflammation) were performed to further elucidate the mechanism of action. Moreover, the acetylcholinesterase (AChE) inhibitory activities of POL, EPP, and its main compounds tangshenoside I, lobetyol, lobetyolin, and lobetyolinin were evaluated. ResultsExperiments have confirmed that both POL and EPP from CR could improve scopolamine-induced spatial learning memory deficits. Both of them could regulate cholinergic function by inhibiting AChE and activating choline acetyltransferase (ChAT) activities. They also could enhance antioxidant defense via increasing the activities of superoxide dismutase and glutathione peroxidase, and anti-inflammatory function through suppressing inflammatory factors (nitric oxide, TNF-α, and IL-6) and regulating gut flora. Besides, in vitro experiments demonstrated that four monomeric compounds and EPP, except POL, exhibited inhibition of AChE activity. ConclusionEPP and POL from CR exert a beneficial effect on learning and memory processes in mice with scopolamine-induced memory impairment. CR may be a promising medicine for preventing and improving learning memory.

Erucic acid ameliorates the lipopolysaccharide‐induced memory deficit in rats through inhibited inflammation cytokines expression/caspase 3/NF‐κB pathways

AbstractErucic acid is a single unsaturated fatty acid that falls under the omega‐9 fatty acid family. It was suggested to treat Wistar rats with lipopolysaccharide (LPS)‐induced memory impairment and minimize cognitive impairment. A total of 30 animals were randomized: group I was normally treated group, group II was administered with LPS, group III was treated with LPS along with erucic acid at the dose of 10 mg kg–1 p.o.–1, group IV was treated with LPS along with erucic acid at 20 mg kg–1 p.o.–1 and group V was the erucic acid per se group provided at the dose of 20 mg kg–1 p.o.–1 per se. Behavioral tests were evaluated by using the Morris water maze and Y‐maze. Biochemical analysis including acetylcholine esterase (AChE), choline acetyltransferase (ChAT), glutathione (GSH), catalase activity (CAT), superoxide dismutase (SOD), and nitric oxide (NO) along with proinflammatory mediators tumor necrosis factor‐α (TNF‐α), interleukin‐1β (IL‐1β), caspase 3, and neuroinflammatory biomarker (nuclear factor kappa B‐NF‐κB) were measured. Erucic acid produced substantial behavioral improvement in the Y‐maze test, including spontaneous alterations and reduced latency time during acquisition, and a longer duration of time in the consolidation phase undergoing the MWM test. Furthermore, erucic acid improved the AChE, proinflammatory markers, and oxidative stress as well as restoring endogenous antioxidant levels, ChAT, caspase 3, and NF‐κB levels. Erucic acid may be a therapeutic component for conditions related to memory disorders such as memory impairment, enhances memory functioning, and protects against neuronal damage.

High-intensity interval training improves long-term memory and increases hippocampal antioxidant activity and BDNF levels in ovariectomized Wistar rats

Menopause is the period in which women cease to produce the hormone estrogen, which can trigger physiological, cognitive, and behavioral changes. In this context, alternatives are needed that can reduce the effects provided by menopause, specifically in terms of cognitive and behavioral aspects. High-intensity interval training (HIIT) is an exercise protocol that has shown the potential to improve cognition by promoting an increase in antioxidant defenses and BDNF levels. Therefore, the aim of this study was to evaluate the effects of HIIT on behavior and hippocampal neurochemistry in ovariectomized adult rats. Four groups of rats were divided into: females without ovariectomy surgery and sedentary (SHAM-SED); females with ovariectomy surgery and sedentary (OVX-SED); females without ovariectomy surgery and trained (SHAM-HIIT); females with ovariectomy surgery and trained (OVX-HIIT). After the surgical procedure and the HIIT protocol, the animals underwent anxiety (elevated plus maze and open field) and memory (novel object recognition) tests. Corticosterone was measured in blood and BDNF levels and redox status were evaluated in the hippocampus. The OVX-SED group showed low BDNF levels and antioxidant enzymes, which may be linked to the observed memory impairments. The HIIT protocol (SHAM-HIIT and OVX-HIIT groups) increased the BDNF levels and antioxidant enzymes in the hippocampus, improving the animals' memory. However, HIIT also led to increased plasma corticosterone and anxiety-like behaviors. The ovariectomy procedure induced memory impairment probably due to reductions in hippocampal BDNF levels and redox imbalance. The HIIT protocol demonstrates promising results as an alternative to improve memory in ovariectomized rats.

Edaravone Improves Streptozotocin-Induced Memory Impairment via Alleviation of Behavioral Dysfunction, Oxidative Stress, Inflammation, and Histopathological Parameters.

Alzheimer's disease (AD), as the main cause of dementia, has a progressive and neurodegenerative pattern with number of cases increasing over the next decades. Therefore, discovering an effective treatment with the ability to invert memory impairment and pathophysiological events of AD seems to be required. The present study performed to investigate the probable effects of Edaravone (EDV) in AD-like disorder induced by intracerebroventricular streptozotocin (ICV-STZ) administration in mice. This study also compares the two different methods of ICV-STZ in the memory impairment induction. NMRI male mice were administrated with 3 mg/kg of STZ for two times during 48 hours span, and after 24 hours, animals were treated with EDV (5 and 10 mg/kg), Donepezil, and Memantine for 14 days. After behavioral tests regarding memory and cognitive function, animals were sacrificed, and the hippocampi were utilized for further analyses. Our results demonstrated that administration of STZ induced memory impairment in the Morris water maze (MWM) test and decreased the discriminative factor in novel object recognition (NOR). The biochemical output shows a significant decrease in ferric reducing antioxidant power (FRAP) and glutathione (GSH) levels followed by increase in malondialdehyde (MDA) and protein carbonylation (PCO) levels. The output showed no difference between the patterns of AD-like disorder induction. Following our treatment groups, administration of EDV (5 and 10 mg/kg), Donepezil, and Memantine significantly improved memory performance and discriminatory behavior. Aforementioned treatments managed to improve FRAP and GSH content of hippocampus, while significantly attenuating MDA, PCO, and nitric oxide overproduction. In addition, no significant difference has been observed between the effect of 5 and 10 mg/kg EDV application. It was supposed that EDV managed to ameliorate memory dysfunction, discriminatory behavior, oxidative stress, and cellular antioxidant power in a dose-independent pattern in mice.

Silymarin pretreatment protects against ethanol-induced memory impairment: Biochemical and histopathological evidence

BackgroundEthanol (Eth.) abuse induces memory impairment. Oxidative damage and apoptosis are considered the likely causes of memory impairment. Silymarin (Sil.) is a flavonoid isolated from the plant Silymarin marianum (milk thistle). While studies have reported the neuroprotective effect of Sil. against neurodegenerative processes, the precise mechanism of action of Sil. in Eth.-induced memory impairment remains unclear. MethodsTwenty-eight rats were equally divided into four groups: Control (saline 1 ml/rat); Sil. (200 mg/kg for 30 days); Eth. (2 g/kg/day for 30 days); and Sil. + Eth. Behavioral tests including inhibitory avoidance and open field were used to investigate memory and locomotion. Brain antioxidant parameters, including catalase, superoxide dismutase, total antioxidant capacity and total thiol group, plus oxidative parameters, including malondialdehyde and total oxidant status, followed by hippocampal apoptosis (Bax/Bcl2, cleaved caspase) and histopathological changes were evaluated in the groups. ResultsWhile the administration of Eth. impaired memory, Sil. significantly reversed Eth-induced memory deficits. Eth. administration also augmented brain oxidative and hippocampal apoptosis parameters. In contrast, a marked reduction in brain antioxidant and anti-apoptotic parameters was observed in the Eth. group. At the tissue level, hippocampal sections from Eth.-treated animals revealed severe neuronal damage. The administration of Sil. to Eth.-treated rats remarkably alleviated all the said Eth.-induced biochemical and histopathological effects. On the contrary, Sil. alone did not change the behavior and biochemical/molecular parameters. ConclusionThe memory-enhancing effect of Sil. in Eth.-induced demented rats may be partly mediated by the augmented antioxidant effects and amelioration of apoptotic and histopathological changes.

Vitamin D Improves Dementia Induced by Scopolamine in Mice: Histological Study

In Dementia, there is a deterioration in cognitive ability, which affect memory, thinking, and the ability to perform daily activities. Vitamin D is a steroid hormone; its deficiency may play an aggressive role in neurodegeneration disorders. Scopolamine is a muscarinic receptor antagonist that induces memory impairment and oxidative stress. The aim of the work is to determine the histological effect of vitamin D on dementia induced by scopolamine in albino mice. Male albino mice were divided into eight groups of six each. Group 1: Administered T80(1%) for one week, Group 2: Administered scopolamine for one week, Group 3: Administered Vitamin D for one week, Group 4: Administered scopolamine plus Vitamin D for one week (prophylactic effect), Group 5: Administered scopolamine for one week, followed by vitamin D administration for another one week (treatment). Group 6: Administered scopolamine for one week, followed by no treatment for another week, Group 7: Administered donepezil as standard to evaluate learning and memory, Group 8: Administered scopolamine plus Donepezil for one week. Drugs were administered by intraperitoneal route, at the volume of 5ml/kg body weight. All drugs were freshly prepared. The transfer latency was measured using plus maze; mice were killed by neck dislocation; the brains were immediately removed, inserted in 10% formalin, and sent to the histology department, for histological study. Vitamin D repairs the histological damage induced by scopolamine; the improvement induced by vitamin D was much better when given with scopolamine as prophylaxis, more than when it is given after dementia is established as treatment. The model of dementia induced by scopolamine is a reversible model.

Dual Role of Low Frequency Magnetic Field on Neuroinflammation Induced Dendritic Trimming And Memory Impairment on Rat Model of Sporadic Alzheimer’s Disease

AbstractBackgroundGliosis and dendritic loss is reported to be secondary to the amyloid beta (Aß) and hyperphosphorylated tau (hp‐tau) production in Alzheimer’s disease(AD) brain. STZ administration is reported to induce sporadic AD. Previous clinical or preclinical studies on effect of rTMS treatment in AD patients or APP23 mice showed cognitive improvement alone or as adjuvant therapy along‐with amelioration of the glial aggravation in the hippocampus. However, studies on the effect of magnetic field stimulation on the gliosis related dendritic trimming in animal models of sporadic AD is elusive. Therefore, in the present study we have looked in to the effect of extremely low frequency magnetic field stimulation (ELF‐MF; 17.96µT, 50Hz, 2hr/day) for one month post‐injection of STZ (bilateral, 3mg/kg).MethodTotal 45 animals were (ethical no. 937/IAEC/2016) randomly divided into five groups: Control, Sham, AD, Sham+MF and AD+MF. After assessing retention of spatial and avoidance memory using Morris water maze and passive avoidance step down test on 30th day, animals were sacrificed and tissues processed for oxidative stress and immunofluorescence, Golgi‐Cox staining.ResultBehavioural analysis revealed spatial memory improvement with no effect on the avoidance memory loss in AD+MF group as compared to AD group. We also found significant decrease in superoxide dismutase, catalase, GSH and increase in malon‐di‐aldehyde (MDA) in AD group. ELF‐MF treatment only reduced MDA level in hippocampus and frontal cortex. GFAP, IBA‐1 and hp‐tau (ser356) positive cells were found to be reduced in AD+MF group, as compared to all groups except Control. Sholl analysis revealed partial improvement of reduction in the number of intersection, bifurcation and length in basal and apical dendrite in the AD group after ELF‐MF treatment in CA3 layer. Convex hull analysis revealed a contradictory result showing reduction in apical (p = 0.018) and increase in basal dendrite (p = 0.038) of AD group as compared to control.ConclusionThese findings suggests dual role of ELF‐MF exposure on STZ model of AD showing improvement of spatial memory by reducing the gliosis induced dendritic loss but loss in avoidance memory.