Unilateral proximal occlusion of the middle cerebral artery has no effect on acquisition or retention of spatial memory

Evaluation of the efficacy of novel therapeutics for potential treatment of Alzheimer's disease (AD) requires an animal model that develops age-related cognitive deficits reproducibly between independent groups of investigators. Herein we assessed comparative temporal changes in spatial memory function in two commercially available transgenic mouse models of AD using the Morris water maze (MWM), incorporating both visible and hidden platform training. Individual cohorts of cDNA-based 'line 85'-derived double-transgenic mice coexpressing the 'Swedish' mutation of amyloid precursor protein (APPSwe) and the presenillin 1 (PS1) 'dE9' mutation were assessed in the MWM at mean ages of 3.6, 9.3 and 14.8months. We found significant deficits in spatial memory retention in APPSwe/PS1dE9 mice aged 3.6months and robust deficits in spatial memory acquisition and retention in APPSwe/PS1dE9 mice aged 9.3months, with a further significant decline by age 14.8months. β-Amyloid deposits were present in brain sections by 7.25months of age. In contrast, MWM studies with individual cohorts (aged 4-21months) of single-transgenic genomic-based APPSwe mice expressing APPSwe on a yeast artificial chromosomal (YAC) construct showed no significant deficits in spatial memory acquisition until 21months of age. There were no significant deficits in spatial memory retention up to 21months of age and β-amyloid deposits were not present in brain sections up to 24months of age. These data, generated using comprehensive study designs, show that APPSwe/PS1dE9 but not APPSwe YAC mice appear to provide a suitably robust model of AD for efficacy assessment of novel AD treatments in development.

Behavioral and molecular effects of intrahippocampal infusion of auraptene, resveratrol, and curcumin on H-89-induced deficits on spatial memory acquisition and retention in Morris water maze.

Estrogen enhances the retention of spatial reference memory in the open field tower task, but disrupts the expression of spatial memory following a novel start position

Mutations in the Cyclin-dependent kinase-like 5 (CDKL5) gene cause severe neurodevelopmental disorders. Recently we have generated Cdkl5 KO mice by targeting exon 2 on the C57BL/6N background, and demonstrated postsynaptic overaccumulation of GluN2B-containing N-methyl-D-aspartate (NMDA) receptors in the hippocampus. In the current study, we subjected the Cdkl5 KO mice to a battery of comprehensive behavioral tests, aiming to reveal the effects of loss of CDKL5 in a whole perspective of motor, emotional, social, and cognition/memory functions, and to identify its undetermined roles. The neurological screen, rotarod, hot plate, prepulse inhibition, light/dark transition, open field, elevated plus maze, Porsolt forced swim, tail suspension, one-chamber and three-chamber social interaction, 24-h home cage monitoring, contextual and cued fear conditioning, Barnes maze, and T-maze tests were applied on adult Cdkl5 -/Y and +/Y mice. Cdkl5 -/Y mice showed a mild alteration in the gait. Analyses of emotional behaviors revealed significantly enhanced anxiety-like behaviors of Cdkl5 -/Y mice. Depressive-like behaviors and social interaction of Cdkl5 -/Y mice were uniquely altered. The contextual and cued fear conditioning of Cdkl5 -/Y mice were comparable to control mice; however, Cdkl5 -/Y mice showed a significantly increased freezing time and a significantly decreased distance traveled during the pretone period in the altered context. Both acquisition and long-term retention of spatial reference memory were significantly impaired. The morphometric analysis of hippocampal CA1 pyramidal neurons revealed impaired dendritic arborization and immature spine development in Cdkl5 -/Y mice. These results indicate that CDKL5 plays significant roles in regulating emotional behaviors especially on anxiety- and fear-related responses, and in both acquisition and long-term retention of spatial reference memory, which suggests that focus and special attention should be paid to the specific mechanisms of these deficits in the CDKL5 deficiency disorder.

Background: Alzheimer’s disease (AD) is one of the most common neurodegenerative syndromes characterized by a progressive decline in the spatial memory. There are convincing evidences on the neuroprotective effects of flavonoids against AD. Aims and Objective: To determine the effect of quercetin on the acquisition and retention of spatial memory in a rat model of AD. Materials and Methods: Twenty-four male Wistar rats were divided into four groups (six in each): group I: control rats receiving intracerebroventricular (ICV) injection of normal saline, group II: rats induced AD by ICV injection of streptozotocin (STZ; 3 mg/kg bilaterally; twice, on days 1 and 3), and groups III and IV: ICV-STZ AD rats treated intraperitoneally (IP) with 40 and 80 mg/kg/day quercetin, respectively, over a period of 12 days. Then, the rats were trained with four trials per day for five consecutive days in the Morris water maze (MWM). On the sixth day, the memory retention was evaluated. Result: The ICV-STZ AD groups showed a significant impairment in the acquisition and retrieval of spatial memory when compared with the control group (P < 0.001). In the AD groups, the escape latency during the training trials showed a significant decrease (P < 0.001). Meanwhile, during the MWM task, these rats spent more time in the target quadrant in probe trials when compared with the controls. Conclusion: Quercetin acted as a spatial memory enhancer in ICV-STZ–induced AD rats. Hence, this flavonoid can be considered potentially as a promising agent for developing prophylactic and therapeutic neuroprotection. This neuroprotective effect of quercetin may be attributed to its antioxidant and scavenging properties.

Alzheimer's disease (AD) is the most common type of neurodegenerative amyloid disorder causing progressive cognitive decline and memory loss. A considerable number of therapies for AD rely on inhibition/delay/dissociation of amyloid beta (Aβ) oligomers and fibrils. In this case, nanoparticles (NPs) demonstrated substantial effects on the Aβ fibrillation process; however, their effects on progressive cognitive decline and memory have been poorly investigated in vivo. In this study, acquisition and retention of spatial learning and memory are studied in a rat animal model of AD after intrahippocampal (IH) and intraperitoneal (IP) injections of a model NP, i.e., gold NPs (AuNPs). The outcomes revealed that the AuNPs could improve the acquisition and retention of spatial learning and memory in Aβ treated rats as indicated by decreased time (Aβ: 39.60 ± 3.23 s vs Aβ+AuNPs: 25.78 ± 2.80 s) and distance (Aβ: 917.98 ± 50.81 cm vs Aβ+AuNPs: 589.09 ± 65.96 cm) of finding the hidden platform during training days and by increased time spent in the target quadrant (Aβ: 19.40 ± 0.98 s vs Aβ+AuNPs: 29.36 ± 1.14 s) in the probe test in Morris water maze (MWM). Expression of brain-derived neurotrophic factor, BDNF, cAMP response element binding protein, CREB, and stromal interaction molecules, e.g., STIM1 and STIM2 was also increased, supporting improved neural survival. Our outcomes may pave a way for mechanistic insights toward the role of NPs on retrieval of the deteriorated behavioral functions in brain tissue after AD outbreak.

Neonatal anoxia in rats: Hippocampal cellular and subcellular changes related to cell death and spatial memory

Mercury is a highly poisonous heavy metal abundantly found in the environment in its inorganic form. Although evidence have been provided about the possible role of inorganic mercury in the pathology of Alzheimer's disease (AD), its effect on cognitive and mitochondrial functions have not yet been completely understood. Thus, the purpose of the present study was to examine the effects of the chronic exposure to mercuric chloride (0.4, 0.8 and 1.6 mg kg-1 per day for 3 weeks) through drinking water (by gavage) on spatial learning and memory and hippocampal mitochondrial function in beta-amyloid treated rats (1 μg per μL per side, intrahippocampally). The acquisition and retention of spatial memory were evaluated by the Morris water maze (MWM) test. Several parameters of hippocampal mitochondrial function were also measured. The results indicated that mercury impaired spatial learning and memory as well as aggravated Aβ-induced memory impairments in a concentration-dependent manner. Furthermore, mercury exposure resulted in a significant increase in ROS generation, MMP collapse, mitochondrial swelling, glutathione oxidation, lipid peroxidation, and outer membrane damage. In addition, a reduced cytochrome c oxidase (complex IV) activity and elevated ADP/ATP ratio in the rats' hippocampus was also observed. The findings of the current study revealed that chronic mercury exposure led to mitochondrial dysfunction, which resulted in spatial memory impairments. The results also showed that mercury can exacerbate the toxic effects of Aβ on spatial memory and hippocampal mitochondrial function.

Facilitative effects of an adenosine A 1/A 2 receptor blockade on spatial memory performance of rats: selective enhancement of reference memory retention during the light period

Objectives: Chronic stress exposure can disrupt the balance of organisms, result in learning and memory impairments and induce oxidative stress. However, there is a lack of safe and effective long-term therapeutic agents for stress-related injuries. Fresh ginseng (FG), an unprocessed raw root of ginseng, has antioxidant and neuroprotective activities and has been used as functional health food in Asian countries for many years. The aim of this study was to verify the protective effects of FG on chronic restraint stress (CRS)-induced learning and memory impairments as well as oxidative stress damage in mice.Methods: Animals were subjected to object location recognition test (OLRT) and novel object recognition test (NORT) to evaluate discriminative ability and spatial learning and memory, and Morris water maze test (MWMT) was used to evaluate the acquisition and retention of spatial memory. In addition, oxidative stress parameters were assessed by measuring the malondialdehyde (MDA) and total antioxidant reactivity levels in serum.Results: Experimental results demonstrated that CRS-induced mice exhibited significantly decreased discrimination index (DI) in OLRT and NORT, longer escape latency and swimming distance, and decreased crossing numbers in MWMT. FG (2 and 6 g/kg) treatment markedly enhanced the discriminative ability by elevating DI in OLRT and NORT, improved the acquisition and retention of spatial memory by decreasing escape latency and swimming distance in the acquisition phase, and increased the crossing numbers in the probe phase of MWMT. Administration of FG (2 and 6 g/kg) significantly reduced the elevated MDA level caused by CRS.Discussion: Our results suggest that FG treatment could improve CRS-induced learning and memory impairments and oxidative stress damage. FG is an intriguing therapeutic agent and functional health food in stress-related dementia.

BackgroundGinseng (Panax ginseng C.A. Meyer) has been used as a traditional herb in the treatment of many medical disorders. Ginsenosides, which are triterpene derivatives that contain sugar moieties, are the main pharmacological ingredients in ginseng. This study was designed to investigate the effect of ginsenoside Rg3-enriched ginseng extract (Rg3GE) on scopolamine-induced memory impairment in mice.MethodsRg3GE (50 and 100 mg/kg) were administered to C57BL/6 mice by oral gavage for 14 days (days 1–14). Memory impairment was induced by scopolamine (1 mg/kg, intraperitoneal injection) for 6 days (days 914). The Morris water maze test was used to assess hippocampus-dependent spatial memory. The effects of scopolamine with or without Rg3GE on acetylcholinesterase and nuclear factor-κB (NF-κB) in the hippocampus were also examined.ResultsMice with scopolamine treatment alone showed impairments in the acquisition and retention of spatial memory. Mice that received Rg3GE and scopolamine showed no scopolamine-induced impairment in the acquisition of spatial memory. Oral administration of Rg3GE suppressed the scopolamine-mediated increase in acetylcholinesterase activity and stimulation of the NF-κB pathway (i.e., phosphorylation of p65) in the hippocampus.ConclusionThese findings suggest that Rg3GE may stabilize scopolamine-induced memory deficits through the inhibition of acetylcholinesterase activity and NF-κB signaling in the hippocampus.

CaMKII Activation in the Entorhinal Cortex Disrupts Previously Encoded Spatial Memory

Phencyclidine affects memory in a nitric oxide-dependent manner: Working and reference memory

Nerve growth factor reverses spatial memory impairments in aged rats

Prior studies suggested that the transcription factor ATF4 negatively regulates synaptic plastic and memory. By contrast, we provide evidence from direct in vitro and in vivo knockdown of ATF4 in rodent hippocampal neurons and from ATF4-null mice that implicate ATF4 as essential for normal synaptic plasticity and memory. In particular, hippocampal ATF4 downregulation produces deficits in long-term spatial memory and behavioral flexibility without affecting associative memory or anxiety-like behavior. ATF4 knockdown or loss also causes profound impairment of both long-term potentiation (LTP) and long-term depression (LTD) as well as decreased glutamatergic function. We conclude that ATF4 is a key regulator of the physiological state necessary for neuronal plasticity and memory.