scholarly journals Palonosetron/Methyllycaconitine Deactivate Hippocampal Microglia 1, Inflammasome Assembly and Pyroptosis to Enhance Cognition in a Novel Model of Neuroinflammation

Molecules ◽  
2021 ◽  
Vol 26 (16) ◽  
pp. 5068
Author(s):  
Reem A. Mohamed ◽  
Dalaal M. Abdallah ◽  
Amany I. El-brairy ◽  
Kawkab A. Ahmed ◽  
Hanan S. El-Abhar
Keyword(s):  
Water Maze ◽  
Amyloid Β ◽  
Novel Object Recognition ◽  
Combination Regimen ◽  
High Fat ◽  
Novel Object ◽  
Α7 Nachr ◽  
Westernized Diet ◽  
Novel Model ◽  
M2 Phenotype

Since westernized diet-induced insulin resistance is a risk factor in Alzheimer’s disease (AD) development, and lipopolysaccharide (LPS) coexists with amyloid β (Aβ)1-42 in these patients, our AD novel model was developed to resemble sporadic AD by injecting LPS into high fat/fructose diet (HFFD)-fed rats. The neuroprotective potential of palonosetron and/or methyllycaconitine, 5-HT3 receptor and α7 nAChR blockers, respectively, was evaluated after 8 days of daily administration in HFFD/LPS rats. All regimens improved histopathological findings and enhanced spatial memory (Morris Water Maze); however, palonosetron alone or with methyllycaconitine promoted animal performance during novel object recognition tests. In the hippocampus, all regimens reduced the expression of glial fibrillary acidic protein and skewed microglia M1 to M2 phenotype, indicated by the decreased M1 markers and the enhanced M2 related parameters. Additionally, palonosetron and its combination regimen downregulated the expression of ASC/TMS1, as well as levels of inflammasome downstream molecules and abated cleaved caspase-1, interleukin (IL)-1β, IL-18 and caspase-11. Furthermore, ACh and 5-HT were augmented after being hampered by the insult. Our study speculates that blocking 5-HT3 receptor using palonosetron overrides methyllycaconitine to combat AD-induced neuroinflammation and inflammasome cascade, as well as to restore microglial function in a HFFD/LPS novel model for sporadic AD.

Cnidoscolus aconitifolius-supplemented diet enhanced neurocognition, endogenous antioxidants and cholinergic system and maintains hippocampal neuronal integrity in male Wistar rats

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Olusegun G. Adebayo ◽  
Samuel A. Onasanwo ◽  
Abayomi M. Ajayi ◽  
Wadioni Aduema ◽  
Oyetola T. Oyebanjo ◽  
...  
Keyword(s):  
Cholinergic System ◽  
Water Maze ◽  
Wistar Rats ◽  
Memory Performance ◽  
Novel Object Recognition ◽  
Object Recognition Test ◽  
Novel Object ◽  
Cnidoscolus Aconitifolius ◽  
Novel Object Recognition Test ◽  
Male Wistar Rats

Abstract Objectives Cnidoscolus aconitifolius have been investigated to have abundant phytochemicals. However, study on the effect of Cnidoscolus aconitifolius on neurobehavioral performance when supplemented with diet is lacking. The study is aimed at investigating the memory-enhancing effect of Cnidoscolus aconitifolius-supplemented diet (CAD) using Morris water maze and Novel object recognition test. Methods Ninety male Wistar rats (80–100 g) were fed with CAD (1, 2.5, 5 and 10%) continuously for a period of 4, 8 and 12 weeks respectively. Six animals per group were used for assessment of memory performance (Morris water maze [MWM] and Novel object recognition test [NORT]); afterwards the brain tissues were harvested for malondialdehyde (MDA), glutathione (GSH) and catalase (CAT) estimation. Acetylcholinesterase (AChE) concentration was also determined. Hippocampal architectural change in the neuron was examined using hematoxylin and eosin (H&E) and cresyl fast violet (Nissl) stain. Results Higher percentage of CAD significantly (p<0.05) improve memory performance with time-dependent effects in rats fed with CAD on MMW and NORT. MDA significantly (p<0.05) reduce in 1 and 2.5% CAD groups at 4th weeks and in 2.5 and 5% CAD groups at 8th weeks while GSH concentration significantly (p<0.05) increase at 12th weeks in 2.5 and 10% CAD groups. However, CAT concentration significantly (p<0.05) increase in 2.5, and 5%, CAD groups, 1, 5, and 10% CAD groups and in 5, and 10% CAD groups at 4th, 8th and 12th weeks. AChE significantly (p<0.05) reduce at 4th and 12th weeks. Histological assessment reveals no neuronal and pyramidal degeneration (chromatolysis) at the hippocampal Cornu Ammonis 3 (CA3) region. Conclusions The results suggest that CAD boost memory performance in rats through positive modulation of oxidative stress, cholinergic system and degeneration of hippocampal neurons.

scholarly journals Deltamethrin Exposure Inhibits Adult Hippocampal Neurogenesis and Causes Deficits in Learning and Memory in Mice

2020 ◽  
Vol 178 (2) ◽  
pp. 347-357
Author(s):  
Muhammad M Hossain ◽  
Abdelmadjid Belkadi ◽  
Sara Al-Haddad ◽  
Jason R Richardson
Keyword(s):  
Object Recognition ◽  
Learning And Memory ◽  
Water Maze ◽  
Cellular Proliferation ◽  
Hippocampal Neurogenesis ◽  
Adult Hippocampal Neurogenesis ◽  
Novel Object Recognition ◽  
Short Term ◽  
Novel Object ◽  
Short Term Exposure

Abstract Deficits in learning and memory are often associated with disruption of hippocampal neurogenesis, which is regulated by numerous processes, including precursor cell proliferation, survival, migration, and differentiation to mature neurons. Recent studies demonstrate that adult born neurons in the dentate gyrus (DG) in the hippocampus can functionally integrate into the existing neuronal circuitry and contribute to hippocampal-dependent learning and memory. Here, we demonstrate that relatively short-term deltamethrin exposure (3 mg/kg every 3 days for 1 month) inhibits adult hippocampal neurogenesis and causes deficits in learning and memory in mice. Hippocampal-dependent cognitive functions were evaluated using 2 independent hippocampal-dependent behavioral tests, the novel object recognition task and Morris water maze. We found that deltamethrin-treated mice exhibited profound deficits in novel object recognition and learning and memory in water maze. Deltamethrin exposure significantly decreased bromodeoxyuridine (BrdU)-positive cells (39%) and Ki67+ cells (47%) in the DG of the hippocampus, indicating decreased cellular proliferation. In addition, deltamethrin-treated mice exhibited a 44% decrease in nestin-expressing neural progenitor cells and a 38% reduction in the expression of doublecortin (DCX), an early neuronal differentiation marker. Furthermore, deltamethrin-exposed mice exhibited a 25% reduction in total number of granule cells in the DG. These findings indicate that relatively short-term exposure to deltamethrin causes significant deficits in hippocampal neurogenesis that is associated with impaired learning and memory.

scholarly journals High fat diet-induced diabetes in mice exacerbates cognitive deficit due to chronic hypoperfusion

2015 ◽  
Vol 36 (7) ◽  
pp. 1257-1270 ◽  
Author(s):  
Kristen L Zuloaga ◽  
Lance A Johnson ◽  
Natalie E Roese ◽  
Tessa Marzulla ◽  
Wenri Zhang ◽  
...  
Keyword(s):  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Cognitive Impairment ◽  
High Fat Diet ◽  
Recognition Task ◽  
Vascular Cognitive Impairment ◽  
Novel Object Recognition ◽  
High Fat ◽  
Novel Object ◽  
Novel Object Recognition Task

Diabetes causes endothelial dysfunction and increases the risk of vascular cognitive impairment. However, it is unknown whether diabetes causes cognitive impairment due to reductions in cerebral blood flow or through independent effects on neuronal function and cognition. We addressed this using right unilateral common carotid artery occlusion to model vascular cognitive impairment and long-term high-fat diet to model type 2 diabetes in mice. Cognition was assessed using novel object recognition task, Morris water maze, and contextual and cued fear conditioning. Cerebral blood flow was assessed using arterial spin labeling magnetic resonance imaging. Vascular cognitive impairment mice showed cognitive deficit in the novel object recognition task, decreased cerebral blood flow in the right hemisphere, and increased glial activation in white matter and hippocampus. Mice fed a high-fat diet displayed deficits in the novel object recognition task, Morris water maze and fear conditioning tasks and neuronal loss, but no impairments in cerebral blood flow. Compared to vascular cognitive impairment mice fed a low fat diet, vascular cognitive impairment mice fed a high-fat diet exhibited reduced cued fear memory, increased deficit in the Morris water maze, neuronal loss, glial activation, and global decrease in cerebral blood flow. We conclude that high-fat diet and chronic hypoperfusion impair cognitive function by different mechanisms, although they share commons features, and that high-fat diet exacerbates vascular cognitive impairment pathology.

scholarly journals Stabilized Low-n Amyloid-β Oligomers Induce Robust Novel Object Recognition Deficits Associated with Inflammatory, Synaptic, and GABAergic Dysfunction in the Rat

2018 ◽  
Vol 62 (1) ◽  
pp. 213-226 ◽  
Author(s):  
William Watremez ◽  
Joshua Jackson ◽  
Bushra Almari ◽  
Samantha L. McLean ◽  
Ben Grayson ◽  
...  
Keyword(s):  
Object Recognition ◽  
Amyloid Β ◽  
Novel Object Recognition ◽  
Novel Object

SB-399885 is a potent, selective 5-HT6 receptor antagonist with cognitive enhancing properties in aged rat water maze and novel object recognition models

2006 ◽  
Vol 553 (1-3) ◽  
pp. 109-119 ◽  
Author(s):  
Warren D. Hirst ◽  
Tania O. Stean ◽  
Derek C. Rogers ◽  
David Sunter ◽  
Pippa Pugh ◽  
...  
Keyword(s):  
Object Recognition ◽  
Receptor Antagonist ◽  
Water Maze ◽  
Novel Object Recognition ◽  
Aged Rat ◽  
Novel Object

Impaired recognition memory and cognitive flexibility in the rat L5–L6 spinal nerve ligation model of neuropathic pain

2016 ◽  
Vol 10 (1) ◽  
pp. 61-73 ◽  
Author(s):  
Orla Moriarty ◽  
Claire L. Gorman ◽  
Fiona McGowan ◽  
Gemma K. Ford ◽  
Michelle Roche ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Cognitive Flexibility ◽  
Water Maze ◽  
Spinal Nerve ◽  
Spinal Nerve Ligation ◽  
Neural Mechanisms ◽  
Novel Object Recognition ◽  
The Novel ◽  
Novel Object ◽  
Ca1 Region

AbstractBackground and aimsAlthough neuropathic pain is known to negatively affect cognition, the neural mechanisms involved are poorly understood. Chronic pain is associated with changes in synaptic plasticity in the brain which may impact on cognitive functioning. The aim of this study was to model neuropathic pain in mid-aged rats using spinal nerve ligation (SNL). Following establishment of allodynia and hyperalgesia, behaviour was assessed in a battery of cognitive tests. Expression of the presynaptic protein, synaptophysin, and its colocalisation with the vesicular GABA and glutamate transporters (vGAT and vGLUT, respectively), was investigated in the medial prefrontal cortex (mPFC) and hippocampus.MethodsNine month old male Sprague Dawley rats underwent L5-L6 spinal nerve ligation or a sham procedure. Mechanical and cold allodynia and thermal hyperalgesia were assessed using von Frey, acetone and Hargreaves tests, respectively. Cognition was assessed in the novel-object recognition, air-puff passive avoidance and Morris water maze behavioural tasks. Immunohistochemistry was used to examine the expression of synaptophysin in the mPFC and CA1 region of the hippocampus and double labelling of synaptophysin and the vesicular transporters vGAT and vGlut was used to investigate the distribution of synaptophysin on GABAergic and glutamatergic neurons.ResultsSNL rats displayed impaired performance in the novel-object recognition task. Passive-avoidance responding, and spatial learning and memory in the Morris water maze, were unaffected by SNL surgery. However, in the water maze reversal task, pain-related impairments were evident during training and probe trials. SNL surgery was not associated with any differences in the expression of synaptophysin or its colocalisation with vGAT or vGLUT in the mPFC or the hippocampal CA1 region.ConclusionsThese results suggest that the SNL model of neuropathic pain is associated with deficits in recognition memory and cognitive flexibility, but these deficits are not associated with altered synaptophysin expression or distribution in the mPFC and CA1.ImplicationsCognitive complaints are common amongst chronic pain patients. Here we modelled cognitive impairment in a well-established animal model of neuropathic pain and investigated the neural mechanisms involved. A better understanding of this phenomenon is an important prerequisite for the development of improved treatment of patients affected.

scholarly journals Early-life status epilepticus induces long-term deficits in anxiety and spatial learning in mice

2017 ◽  
Vol 04 (01) ◽  
pp. 036-045
Author(s):  
Gregory Smith ◽  
Nowrin Ahmed ◽  
Erin Arbuckle ◽  
Joaquin Lugo
Keyword(s):  
Status Epilepticus ◽  
Object Recognition ◽  
Early Life ◽  
Water Maze ◽  
Elevated Plus Maze ◽  
Novel Object Recognition ◽  
Novel Object ◽  
Plus Maze ◽  
Marble Burying

Abstract Background One of the most devastating aspects of developmental epilepsy is the long-term impact on behavior. Children with epilepsy show a high co-morbidity with anxiety disorders and autism. Methods To examine whether early-life status epilepticus results in altered anxiety, repetitive behavior, social behavior, and learning and memory, we induced status epilepticus in male C57BL/6 mice on postnatal day (PD) 10. The mice received intraperitoneal injections of either kainic acid (2 mg/kg) or 0.9% normal saline. We also included a nontreated control group. Kainic acid induced status epilepticus for approximately 1.5 h. At PD60, the adult mice were then tested in a battery of behavioral tasks, including open field activity, elevated-plus maze, light-dark test, marble burying, social chamber, social partition, conditioned fear, novel object recognition, and Morris water maze. Results The early-life seizure group showed consistent increases in anxiety in the open field test (p < 0.05), elevated plus maze (p < 0.05), and light-dark task (p < 0.01). The seizure group showed significant (p < 0.01) impairment in the Morris water maze. There were no differences observed in marble burying, social partition, social chamber, novel object recognition, or delay fear conditioning tasks. Conclusions These results demonstrate that a single insult of status epilepticus during the neonatal period is sufficient to cause specific, long-term impairments in anxiety and spatial learning.

scholarly journals Cognitive deficits and increases in creatine precursors in a brain-specific knockout of the creatine transporter gene Slc6a8

2017 ◽  
Author(s):  
Kenea C. Udobi ◽  
Amanda N. Kokenge ◽  
Emily R. Hautman ◽  
Gabriela Ullo ◽  
Julie Coene ◽  
...  
Keyword(s):  
Cognitive Deficits ◽  
Water Maze ◽  
Memory Deficits ◽  
Whole Body ◽  
Novel Object Recognition ◽  
Transporter Gene ◽  
Biochemical Phenotype ◽  
Creatine Transporter ◽  
Novel Object ◽  
Path Lengths

AbstractCreatine transporter (CrT; SLC6A8) deficiency (CTD) is an X-linked disorder characterized by severe cognitive deficits, impairments in language, and an absence of brain creatine (Cr). In a previous study, we generated floxed Slc6a8 (Slc6a8flox) mice to create ubiquitous Slc6a8 knockout (Slc6a8-/y) mice. Slc6a8-/y mice lacked whole body Cr and exhibited cognitive deficits. While Slc6a8-/y mice have a similar biochemical phenotype to CTD patients, they also showed a reduction in size and reductions in swim speed that may have contributed to the observed deficits. To address this, we created brain-specific Slc6a8 knockout (bKO) mice by crossing Slc6a8Flox mice with Nestin-cre mice. bKO mice had reduced cerebral Cr levels while maintaining normal Cr levels in peripheral tissue. Interestingly, brain concentrations of the Cr synthesis precursor guanidinoacetic acid were increased in bKO mice. bKO mice had longer latencies and path lengths in the Morris water maze, without reductions in swim speed. In accordance with data from Slc6a8-/y mice, bKO mice showed deficits in novel object recognition as well as contextual and cued fear conditioning. bKO mice were also hyperactive, in contrast with data from the Slc6a8-/ymice. The results demonstrate that the loss of cerebral Cr is responsible for the learning and memory deficits seen in ubiquitous Slc6a8-/y mice.

scholarly journals Cognitive-Enhancing Effect of a Hydroethanolic Extract of Crinum macowanii against Memory Impairment Induced by Aluminum Chloride in BALB/c Mice

2018 ◽  
Vol 2018 ◽  
pp. 1-10
Author(s):  
Mohammed S. Jilani ◽  
Dexter Tagwireyi ◽  
Louis L. Gadaga ◽  
Charles C. Maponga ◽  
Cosmas Mutsimhu
Keyword(s):  
Aluminum Chloride ◽  
Water Maze ◽  
Memory Impairment ◽  
Recognition Task ◽  
Novel Object Recognition ◽  
The Novel ◽  
Novel Object ◽  
Object Recognition Task ◽  
Novel Object Recognition Task ◽  
Hydroethanolic Extract

Crinum macowanii is a bulbous plant indigenous to many parts of Southern Africa. Extracts of C. macowanii have gained interest since the discovery of various alkaloids, few of which possess acetylcholinesterase inhibitory activity. The present study was performed to evaluate the effect of a crude hydroethanolic extract of C. macowanii against aluminum chloride-induced memory impairment in mice using the Morris water maze and the novel object recognition task. C. macowanii (10, 20, and 40 mg/kg p.o) was administered daily for five weeks, while donepezil (3 mg/kg p.o) was used as the positive control. C. macowanii at a dosage of 40 mg/kg showed a significantly lower escape latency than the negative control (P<0.0001) and was found to be comparable to donepezil 3 mg/kg in the Morris water maze test. C. macowanii at 40 mg/kg exhibited a significantly higher discrimination index than aluminum chloride-treated mice in the novel object recognition task. The results may support the usefulness of C. macowanii in the management of dementia and related illnesses.

scholarly journals Exercise Training Results in Lower Amyloid Plaque Load and Greater Cognitive Function in an Intensity Dependent Manner in the Tg2576 Mouse Model of Alzheimer’s Disease

2020 ◽  
Vol 10 (2) ◽  
pp. 88
Author(s):  
Riya Thomas ◽  
Scott D. Zimmerman ◽  
Kayla M. Yuede ◽  
John R. Cirrito ◽  
Leon M. Tai ◽  
...  
Keyword(s):  
Object Recognition ◽  
Cognitive Function ◽  
Exercise Training ◽  
Water Maze ◽  
Amyloid Plaque ◽  
Novel Object Recognition ◽  
Dependent Manner ◽  
Novel Object ◽  
Plaque Load ◽  
Tg2576 Mice

Three months of exercise training (ET) decreases soluble Aβ40 and Aβ42 levels in an intensity dependent manner early in life in Tg2576 mice (Moore et al., 2016). Here, we examined the effects of 12 months of low- and high- intensity exercise training on cognitive function and amyloid plaque load in the cortex and hippocampus of 15-month-old Tg2576 mice. Low- (LOW) and high- (HI) intensity ET animals ran at speeds of 15 m/min on a level treadmill and 32 m/min at a 10% grade, respectively, for 60 min/day, five days/week, from 3 to 15 months of age. Sedentary mice (SED) were placed on a level, non-moving, treadmill for the same duration. ET mice demonstrated a significantly lower amyloid plaque load in the cortex and hippocampus that was intensity dependent. Improvement in cognitive function, assessed by Morris Water Maze and Novel Object Recognition tests, was greater in the HI group compared to the LOW and SED groups. LOW mice performed better in the initial latency to the platform location during the probe trial of the Morris Water Maze (MWM) test than SED, but not in any other aspect of MWM or the Novel Object Recognition test. The results of this study indicate that exercise training decreases amyloid plaque load in an intensity dependent manner and that high-intensity exercise training improves cognitive function relative to SED mice, but the intensity of the LOW group was below the threshold to demonstrate robust improvement in cognitive function in Tg2576 mice.

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