Memory Impairment In Animal Model Research Articles

The Development of a Regulator of Human Serine Racemase for N-Methyl-D-aspartate Function.

It is crucial to regulate N-methyl-D-aspartate (NMDA) function bivalently depending on the central nervous system (CNS) conditions. CNS disorders with NMDA hyperfunction are involved in the pathogenesis of neurotoxic and/or neurodegenerative disorders with elevated D-serine, one of the NMDA receptor co-agonists. On the contrary, NMDA-enhancing agents have been demonstrated to improve psychotic symptoms and cognition in CNS disorders with NMDA hypofunction. Serine racemase (SR), the enzyme regulating both D- and L-serine levels through both racemization (catalysis from L-serine to D-serine) and β-elimination (degradation of both D- and L-serine), emerges as a promising target for bidirectional regulation of NMDA function. In this study, we explored using dimethyl malonate (DMM), a pro-drug of the SR inhibitor malonate, to modulate NMDA activity in C57BL/6J male mice via intravenous administration. Unexpectedly, 400 mg/kg DMM significantly elevated, rather than decreased (as a racemization inhibitor), D-serine levels in the cerebral cortex and plasma. This outcome prompted us to investigate the regulatory effects of dodecagalloyl-α-D-xylose (α12G), a synthesized tannic acid analog, on SR activity. Our findings showed that α12G enhanced the racemization activity of human SR by about 8-fold. The simulated and fluorescent assay of binding affinity suggested a noncooperative binding close to the catalytic residues, Lys56 and Ser84. Moreover, α12G treatment can improve behaviors associated with major CNS disorders with NMDA hypofunction including hyperactivity, prepulse inhibition deficit, and memory impairment in animal models of positive symptoms and cognitive impairment of psychosis. In sum, our findings suggested α12G is a potential therapeutic for treating CNS disorders with NMDA hypofunction.

Synthesis, in silico Studies and Pharmacological Evaluation of a New Series of Indanone Derivatives as Anti-Parkinsonian and Anti-Alzheimer's Agents.

Parkinson's disease (PD) and Alzheimer's disease (AD) are the most common forms of neurodegenerative disorders. The aim of the current work is to study the potential of some new indanone derivatives for the treatment of these neurological disorders. A new series of 4-(2-oxo-2-aminoethoxy)-2-benzylidene substituted indanone derivatives have been synthesized and studied for anti-Parkinsonian and anti-Alzheimer's effects. Substitution of different aminoalkyl functionalities at the para position of 2-benzylidene moiety of indanone ring resulted in the formation of potent anti-parkinsonian and anti-Alzheimer's agents (5-10). The neuroprotective effects of newly synthesized compounds were evaluated using perphenazine (PPZ)-induced catatonia in rats and LPS-induced cognitive deficits in mice models. Further, in silico molecular modelling studies of the new indanone derivatives were performed by docking against the 3D structures of various neuroinflammatory mediators, such as interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α) and monoamine oxidase-B (MAO-B), to gain the mechanistic insights of their anti-Alzheimer's and antiparkinsonian effects. The newly synthesized indanone analogues 5-10 were found effective against PPZinduced motor dysfunction and LPS-induced memory impairment in animal models. Among all the synthesized analogues, morpholine-substituted indanone 9 displayed maximum anti-parkinsonian activity, even better than the standard drug L-DOPA, while pyrrolidine and piperidine substituted analogues 5 and 6 were found to be the most potent anti-Alzheimer's agents. The new 2-arylidene-1-indanone analogues show good potential as promising leads for designing compounds against Parkinson's and Alzheimer's diseases.

Evaluation of Chenopodium Quinoa Extract on Diazepam Induced Memory Impairment in Animal Models

Aim: The present study explored the pharmacological and insilico studies of ethanolic seed extract of Chenopodium quinoa.
 Materials and Methods: The screening of in vivo anti- amnesic activity of the ethanolic seed extract of Chenopodium quinoa was carried out using Actophotometer and Rotarod apparatus. The extract exhibited active constituents like myristic acid, palmitic acid, eicosadienoic acid, pentadecanoic acid, tocopherols, stigmasterol, β-sitosterol, quercetin, benzoic acid, kaempferol, arachidonic acid, benzofuran and 2-bromodecanoic acid. In silico approaches like docking studies (Mcule software) and Ramchandran plot (procheck), online softwares were used in the study to establish mechanism of action of active constituents present in the extract.
 Results: The extract treated groups at doses (200 mg/kg and 400 mg/kg, bd.wt) showed significant anti-amnesic activity. The basal activity score in actophotometer is as an indicator for impairment of learning and memory. Fall of time by rotarod is used to evaluate learning and memory in rodent models of CNS disorders as in case of amnesia. The results revealed that quercetin, kaempferol, myristic acid, palmitic acid, stigmasterol, lenolenic acid, pentadecanoic acid, tocopherols, arachidonic acid and standard donepezil have got highest glide scores against selected Protein Data Bank (PDB ID): 1EVE, 2FY4, 7CUM and 3EJ8. According to Ramachandran plot a good quality model would be expected to have over 90% in the most favoured region. Proteins like PDB ID: 1EVE, 2FY4, 7CUM and 3EJ8 showed almost 80-90% favoured region which clearly indicates that the selected proteins in the present study are of good quality.
 Conclusion: Our research unveiled that ethanolic seed extract of Chenopodium quinoa possessed significant anti- amnesic activity.

Nanotechnology Therapy for Alzheimer's Disease Memory Impairment Attenuation.

Currently, there is no cure for Alzheimer’s disease (AD) in humans; treatment is symptomatic only. Aging of the population, together with an unhealthy diet and lifestyle, contribute to the steady, global increase of AD patients. This increase creates significant health, societal and economical challenges even for the most developed countries. AD progresses from an asymptomatic stage to a progressively worsening cognitive impairment. The AD cognitive impairment is underpinned by progressive memory impairment, an increasing inability to recall recent events, to execute recently planned actions, and to learn. These changes prevent the AD patient from leading an independent and fulfilling life. Nanotechnology (NT) enables a new, alternative pathway for development of AD treatment interventions. At present, the NT treatments for attenuation of AD memory impairment are at the animal model stage. Over the past four years, there has been a steady increase in publications of AD animal models with a wide variety of original NT treatment interventions, able to attenuate memory impairment. NT therapy development, in animal models of AD, is faced with the twin challenges of the nature of AD, a chronic impairment, unique to human, of the tau protein and A β peptides that regulate several key physiological brain processes, and the incomplete understanding of AD′s aetiology. This paper reviews the state-of-the-art in NT based treatments for AD memory impairment in animal models and discusses the future work for translation to the successful treatment of AD cognitive impairment in human.

Neuro-protective Effect of Ayurveda Formulation, Saraswatharishtam, on Scopolamine Induced Memory Impairment in Animal Model

Introduction: In the management of neurodegenerative and neuropsychiatric diseases, memory loss remains very challenging. Saraswatharishtam (SWRT) is an ayurvedic formulation prescribed for several neurological ailments like acute anxiety, partial memory loss, slurred speech, neuro-degenerative diseases like Parkinson’s, Alzheimer’s etc. Methods: Present study explores the possibilities of curative effects of SWRT on Scopolamine induced memory impairment and to compare the effects of commonly used drug Piracetam. Adult Wistar Swiss albino mice were used for this experiment and divided into five different groups for the treatments of the drugs in various combinations. The first group was vehicle treated control while the second group was treated with scopolamine to induce memory impairment. The third groups of animals were treated with Scopolamine where the mice were pretreated with standard neuro-protective drug Piracetam, while the fourth and fifth groups of animals were treated with scopolamine and the animals were pretreated with SWRT at the doses of 200 and 400 mg/kg respectively to compare with the effect of Piracetam. Scopolamine was administered on day eight, only for 45 minutes in all the cases (Group I- Group V). Several neurobehavioral parameters were examined to confirm the neuro-protective effects of SWRT. Results: Saraswatharishtam significantly reversed the memory loss in mice model as revealed from elevated plus maze, radial maze and rectangular maze experiments justifying its neuroprotective potential as observed in usually used synthetic Piracetam. SWRT was found to be nontoxic and very promising antioxidant recorded from acute and chronic toxicological studies. Conclusions: It is suggested that SWRT, could be used as safe and easily available Ayurveda medicine to treat neurological dysfunctions without any side effects. Further translational research is needed to explore its neuro-protective potential.

Neuro-protective Effect of Ayurveda Formulation, Saraswatharishtam, on Scopolamine Induced Memory Impairment in Animal Model

Introduction: In the management of neurodegenerative and neuropsychiatric diseases, memory loss remains very challenging. Saraswatharishtam (SWRT) is an ayurvedic formulation prescribed for several neurological illnesses like acute anxiety, partial memory loss, slurred speech, neuro degenerative diseases like Parkinson’s, Alzheimer’s etc. Methods: Present study explores the possibilities of curative effects of SWRT on Scopolamine induced memory impairment and to compare the effects of commonly used drug piracetam. Adult Wistar Swiss albino mice were used for this experiment and divided into five different groups for the treatments of the drugs in various combinations. The first group was vehicle treated control while the second group was treated with scopolamine to induce memory impairment. The third group of animals were treated with Scopolamine where the mice were pretreated with standard neuroprotective drug Piracetam, while the fourth and fifth group of animals were treated with scopolamine and the animals were pretreated with SWRT at the doses of 200 and 400 mg/kg respectively to compare with the effect of Piracetam. Scopolamine was administered on day eight, only for 45 minutes in all the cases (Group I- Group V). Several neurobehavioral parameters were examined to confirm the neuroprotective effects of SWRT. Results: Saraswatharishtam significantly reversed the memory loss in mice model revealed from elevated plus maze, radial maze and rectangular maze experiments justifying its neuroprotective potential as observed in usually used synthetic Piracetam. SWRT was found to be nontoxic and very promising antioxidant recorded from acute and chronic toxicological studies. Conclusions: It is suggested that SWRT, could be used as safe and easily available Ayurveda medicine to treat neurological dysfunctions without any side effects. Further translational research is needed to explore its neuro-protective potential.

Diphtheria toxoid nanoparticles improve learning and memory impairment in animal model of Alzheimer's disease.

Alzheimer's disease (AD) is a neurodegenerative disorder involving memory. The present study aimed at evaluating the effects of encapsulated diphtheria toxoid (DT) on behavioral learning impairment, and XBP1 mRNA splicing in AD. A DT-loaded nanoparticle (NP) carrier was prepared using the ionic gelation method. Sixty-three rats were divided into nine groups: (1) healthy, (2-4) sham, and (5-9) AD models: (5) AD was induced by intracerebroventricular injection of amyloid beta (Aβ) 1-42. (6) The rats received a subcutaneous diphtheria vaccine only 28 days before Aβ injection. (7) The rats received an intranasal diphtheria vaccine, in group 8, induced by administering empty chitosan NPs. 9) it was induced by administering chitosan NPs carrying DT. Morris water maze (MWM) test was used to examine the animals' learning and memory. Also, X-box binding protein 1 (XBP-1) mRNA gene splicing was studied in the hippocampus by reverse-transcription polymerase chain reaction (RT-PCR). For the first time, chitosan NPs were prepared with an average diameter size of 40 nm and the effectiveness of approximately 70% during DT encapsulation. In comparison with the healthy group, the AD models exhibited significant impairment of learning and memory (P < 0.05), while DT-administrated animals showed significant improvements in learning and memory impairment (P < 0.05). XBP-1 mRNA gene splicing was only detected in an untreated AD group, while encapsulated DT completely inhibited splicing. The therapeutic effects of DT chitosan NPs against learning and memory impairment were observed in this study, and XBP1 mRNA splicing was reported in the animal models.

Phosphodiesterase-4 inhibitors ameliorates cognitive deficits in deoxycorticosterone acetate induced hypertensive rats via cAMP/CREB signaling system

Phosphodiesterase-4 (PDE-4) inhibitors promote memory by blocking the degradation of cAMP. Existing evidence also shows that neuronal survival and plasticity are dependent on the phosphorylation of cAMP-response element-binding protein. In this regard, PDE-4 inhibitors have also been shown to reverse pharmacologically and genetically induced memory impairment in animal models. In the present study, the authors examined the effect of both rolipram and roflumilast (PDE-4 inhibitors) on the impairment of learning and memory observed in hypertensive rats. Deoxycorticosterone acetate (DOCA) salt hypertensive model was used to induce learning and memory deficits. The mRNA expression of different PDE-4 subtypes along with the protein levels of pCREB and BDNF in the hippocampus was quantified. Systolic blood pressure was significantly increased in DOCA salt hypertensive rats when compared to sham operated rats. This effect was reversed by clonidine, an α2 receptor agonist, while PDE-4 inhibitors did not. PDE-4 inhibitors significantly improved the time-induced memory deficits in object recognition task (ORT). In DOCA salt hypertensive rats, the gene expression of PDE-4B and PDE-4D was significantly increased. Furthermore, both pCREB and BDNF showed decreased levels of expression in hypertensive rats in comparison to sham operated rats. Repeated administration of PDE-4 inhibitors significantly decreased both PDE-4B and PDE-4D with an increase in the expression of pCREB and BDNF in hypersensitive rats. Also, rolipram, roflumilast and roflumilast N-oxide showed a linear increase in the plasma and brain concentrations after ORT. Our present findings suggested that PDE-4 inhibitors ameliorate hypertension-induced learning impairment via cAMP/CREB signaling that regulates BDNF expression downstream in the rat hippocampus.

6-Shogaol, an active constituent of ginger, attenuates neuroinflammation and cognitive deficits in animal models of dementia

Recently, increased attention has been directed towards medicinal extracts as potential new drug candidates for dementia. Ginger has long been used as an important ingredient in cooking and traditional herbal medicine. In particular, ginger has been known to have disease-modifying effects in Alzheimer's disease (AD). However, there is no evidence of which constituents of ginger exhibit therapeutic effects against AD. A growing number of experimental studies suggest that 6-shogaol, a bioactive component of ginger, may play an important role as a memory-enhancing and anti-oxidant agent against neurological diseases. 6-Shogaol has also recently been shown to have anti-neuroinflammatory effects in lipopolysaccharide (LPS)-treated astrocytes and animal models of Parkinson’s disease, LPS-induced inflammation and transient global ischemia. However, it is still unknown whether 6-shogaol has anti-inflammatory effects against oligomeric forms of the Aβ (AβO) in animal brains. Furthermore, the effects of 6-shogaol against memory impairment in dementia models are also yet to be investigated. In this study, we found that administration of 6-shogaol significantly reduced microgliosis and astrogliosis in intrahippocampal AβO-injected mice, ameliorated AβO and scopolamine-induced memory impairment, and elevated NGF levels and pre- and post-synaptic marker in the hippocampus. All these results suggest that 6-shogaol may play a role in inhibiting glial cell activation and reducing memory impairment in animal models of dementia.

Laser Acupuncture at HT7 Acupoint Improves Cognitive Deficit, Neuronal Loss, Oxidative Stress, and Functions of Cholinergic and Dopaminergic Systems in Animal Model of Parkinson's Disease.

To date, the therapeutic strategy against cognitive impairment in Parkinson's disease (PD) is still not in satisfaction level and requires novel effective intervention. Based the oxidative stress reduction and cognitive enhancement induced by laser acupuncture at HT7, the beneficial effect of laser acupuncture at HT7 against cognitive impairment in PD has been focused. In this study, we aimed to determine the effect of laser acupuncture at HT7 on memory impairment, oxidative stress status, and the functions of both cholinergic and dopaminergic systems in hippocampus of animal model of PD. Male Wistar rats, weighing 180–220 g, were induced unilateral lesion at right substantianigra by 6-OHDA and were treated with laser acupuncture continuously at a period of 14 days. The results showed that laser acupuncture at HT7 enhanced memory and neuron density in CA3 and dentate gyrus. The decreased AChE, MAO-B, and MDA together with increased GSH-Px in hippocampus of a 6-OHDA lesion rats were also observed. In conclusion, laser acupuncture at HT7 can improve neuron degeneration and memory impairment in animal model of PD partly via the decreased oxidative stress and the improved cholinergic and dopaminergic functions. More researches concerning effect of treatment duration are still required.

SILKWORM PUPAE PROTECT AGAINST ALZHEIMER&amp;rsquo;S DISEASE

Silkworm ( Bombyx mori) pupae have long been used as food and medicine in Asian countries. It is reputed for the treatment of numerous neurological disorders re lated to oxidative stress including stroke. Therefo re, we hypothesized that silkworm pupae could attenuate memory impairment and neurodegeneration in Alzheimer’s disease. In the present study, we determined the ef fect of silkworm pupae on the neurodegeneration and memory impairment in animal model of Alzheimer’s disease. Adult male Wistar rats, weighing 180-220 g, were orally given the silkworm pupae at doses of 60, 90 and 135 mg kg -1 BW 14 days before and 7 days after the bilateral administration of AF64A, a cholinotoxin, via intrac erebroventricular route. The animals were determined the memory using Morris water maze test and determined the density of neurons in hippocampus. All doses of silkworm pupae used in this study significantly mit igated the memory impairment and the decreased neurons density in hippocampus. To explore the possible und erlying mechanism of the cognitive enhancing effect and neuroprotective effect, the activity of acetylcholi nesterase enzyme and the Malondialdehyde (MDA), the oxidative marker were determined respectively. Our results clearly demonstrated that the cognitive enh ancing effect of silkworm pupae occurred at least via the increased cholinergic function while its neuroprote ctive effect occurred via the decrease oxidative stress. In conc lusion, silkworm pupae appear to be the potential f unctional food to protect against Alzheimer’s disease.

P–441 - AC-3933, a novel cognitive enhancer: II. Effects on memory impairment in animal models.

P–441 - AC-3933, a novel cognitive enhancer: II. Effects on memory impairment in animal models.

Effects of TRH and Its Analogue, DN-1417, on Memory Impairment in Animal Models

Effects of TRH and Its Analogue, DN-1417, on Memory Impairment in Animal Models

Effects of TRH and Its Analogue, DN-1417, on Memory Impairment in Animal Models

Effects of TRH and Its Analogue, DN-1417, on Memory Impairment in Animal Models