Surgery Trauma Severity but not Anesthesia Length Contributes to Postoperative Cognitive Dysfunction in Mice

Background: Perioperative, modifiable factors contributing to perioperative neurocognitive disorders (PND) have not been clearly defined. Objective: To determine the contribution of anesthesia lengths and the degrees of surgical trauma to PND and neuroinflammation, a critical process for PND. Methods: Three-month-old C57BL/6J mice were subjected to 2 h or 6 h isoflurane anesthesia plus a 5 min or 15 min left common carotid artery exposure (surgery) in a factorial design (two factors: anesthesia with two levels and surgery with three levels). Their learning and memory were tested by Barnes maze and novel object recognition paradigms. Blood, spleen, and hippocampus were harvested for measuring interleukin (IL)-6 and IL-1β. Eighteen-month-old C57BL/6J mice (old mice) were subjected to 6 h isoflurane anesthesia or 2 h isoflurane anesthesia plus 15 min surgery and then had learning and memory tested. Results: Three-month-old mice with 15 min surgery (long surgery) under 2 h or 6 h anesthesia performed poorly in the learning and memory tests compared with controls. Anesthesia alone or anesthesia plus 5 min surgery did not affect mouse performance in these tests. Similarly, only mice with long surgery but not mice with other experimental conditions had increased IL-6 and IL-1β in the blood, spleen, and hippocampus and decreased spleen weights. Splenocytes were found in the hippocampus after surgery. Similarly, old mice with long surgery but not the mice with isoflurane anesthesia alone had poor performance in the Barnes maze and novel object recognition tests. Conclusion: Surgical trauma, but not anesthesia, contributes to the development of PND and neuroinflammation. Splenocytes may modulate these processes.

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

Toxicological Sciences ◽

10.1093/toxsci/kfaa144 ◽

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.

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PT3: A Novel Benzamide Class Histone Deacetylase 3 Inhibitor Improves Learning and Memory in Novel Object Recognition Mouse Model

ACS Chemical Neuroscience ◽

10.1021/acschemneuro.0c00721 ◽

2021 ◽

Author(s):

Sravani Pulya ◽

Ashutosh Mahale ◽

Yamini Bobde ◽

Ganesh Routholla ◽

Tarun Patel ◽

...

Keyword(s):

Object Recognition ◽

Mouse Model ◽

Learning And Memory ◽

Histone Deacetylase ◽

Novel Object Recognition ◽

Novel Object ◽

Histone Deacetylase 3

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Effects of Melatonin on Neurobehavior and Cognition in a Cerebral Palsy Model of plppr5−/− Mice

Frontiers in Endocrinology ◽

10.3389/fendo.2021.598788 ◽

2021 ◽

Vol 12 ◽

Author(s):

Yuxiao Sun ◽

Liya Ma ◽

Meifang Jin ◽

Yuqin Zheng ◽

Dandan Wang ◽

...

Keyword(s):

Spinal Cord ◽

Cerebral Palsy ◽

Object Recognition ◽

Brain Injury ◽

Learning And Memory ◽

Brain Damage ◽

Novel Object Recognition ◽

Wild Type ◽

Novel Object ◽

The Brain

Cerebral palsy (CP), a group of clinical syndromes caused by non-progressive brain damage in the developing fetus or infant, is one of the most common causes of lifelong physical disability in children in most countries. At present, many researchers believe that perinatal cerebral hypoxic ischemic injury or inflammatory injury are the main causes of cerebral palsy. Previous studies including our works confirmed that melatonin has a protective effect against convulsive brain damage during development and that it affects the expression of various molecules involved in processes such as metabolism, plasticity and signaling in the brain. Integral membrane protein plppr5 is a new member of the plasticity-related protein family, which is specifically expressed in brain and spinal cord, and induces filopodia formation as well as neurite growth. It is highly expressed in the brain, especially in areas of high plasticity, such as the hippocampus. The signals are slightly lower in the cortex, the cerebellum, and in striatum. Noteworthy, during development plppr5 mRNA is expressed in the spinal cord, i.e., in neuron rich regions such as in medial motor nuclei, suggesting that plppr5 plays an important role in the regulation of neurons. However, the existing literature only states that plppr5 is involved in the occurrence and stability of dendritic spines, and research on its possible involvement in neonatal ischemic hypoxic encephalopathy has not been previously reported. We used plppr5 knockout (plppr5−/−) mice and their wild-type littermates to establish a model of hypoxicischemic brain injury (HI) to further explore the effects of melatonin on brain injury and the role of plppr5 in this treatment in an HI model, which mainly focuses on cognition, exercise, learning, and memory. All the tests were performed at 3–4 weeks after HI. As for melatonin treatment, which was performed 5 min after HI injury and followed by every 24h. In these experiments, we found that there was a significant interaction between genotype and treatment in novel object recognition tests, surface righting reflex tests and forelimb suspension reflex tests, which represent learning and memory, motor function and coordination, and the forelimb grip of the mice, respectively. However, a significant main effect of genotype and treatment on performance in all behavioral tests were observed. Specifically, wild-type mice with HI injury performed better than plppr5−/− mice, regardless of treatment with melatonin or vehicle. Moreover, treatment with melatonin could improve behavior in the tests for wild-type mice with HI injury, but not for plppr5−/− mice. This study showed that plppr5 knockout aggravated HI damage and partially weakened the neuroprotection of melatonin in some aspects (such as novel object recognition test and partial nerve reflexes), which deserves further study.

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Effect of chronic exposure of Losartan in mouse prenatal alcohol exposure (PAE) model

European Psychiatry ◽

10.1016/j.eurpsy.2017.01.932 ◽

2017 ◽

Vol 41 (S1) ◽

pp. S600-S600

Author(s):

A. Takyi

Keyword(s):

Object Recognition ◽

Learning And Memory ◽

Prenatal Alcohol Exposure ◽

Alcohol Exposure ◽

Novel Object Recognition ◽

The Novel ◽

Novel Object ◽

Beneficial Effects ◽

Prenatal Alcohol ◽

Competing Interest

Background and aimsFoetal alcohol syndrome (FAS) is a condition that currently affects 1% of babies born in Europe and North America. It is characterised by memory impairment, developmental delay and distinctive facial features. This research uses a mouse prenatal alcohol exposure (PAE) model to explore the effects of PAE on learning, memory and to explore the potentially beneficial effects of common drugs previously shown to have cognitive enhancing effects in both humans and animals.MethodsSixty mice (M = 30 F = 30) C57 mice were exposed to 5% ethanol throughout pregnancy. After weaning the offspring received Losartan (10 mg/kg) via their drinking water for 8 weeks. At 3 months, learning and memory was assessed using the novel object recognition paradigm.ResultsPAE caused a significant decrease in offspring body weight. Treatment with Losartan caused no growth impairment or renal damage. Novel object recognition indicated that PAE caused male offspring to spend significantly less time exploring the novel object than controls and that treatment with Losartan had the effect of improving awareness of the novel object both in the control and alcohol group and decreasing anxiety (P ≤ 0.05). A significant opposite effect was noticed in the female alcohol progeny when compared to the male alcohol progeny (P ≤ 0.05). Losartan in female alcohol progeny had no effect on anxiety. Male control Losartan spent more time exploring the novel object than male alcohol Losartan (P ≤ 0.05).ConclusionsLosartan had no deleterious effects on the development of the animals, and was able to improve learning and memory in control animals without effect in PAE mice.Disclosure of interestThe author has not supplied his declaration of competing interest.

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Novel Object Recognition Test for the Investigation of Learning and Memory in Mice

Journal of Visualized Experiments ◽

10.3791/55718 ◽

2017 ◽

Cited By ~ 52

Author(s):

Lindsay M. Lueptow

Keyword(s):

Object Recognition ◽

Learning And Memory ◽

Recognition Test ◽

Novel Object Recognition ◽

Object Recognition Test ◽

Novel Object ◽

Novel Object Recognition Test

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NBM-T-L-BMX-OS01, Semisynthesized from Osthole, Is a Novel Inhibitor of Histone Deacetylase and Enhances Learning and Memory in Rats

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2013/514908 ◽

2013 ◽

Vol 2013 ◽

pp. 1-18 ◽

Cited By ~ 5

Author(s):

Ying-Chen Yang ◽

Chia-Nan Chen ◽

Carol-Imei Wu ◽

Wei-Jan Huang ◽

Tsun-Yung Kuo ◽

...

Keyword(s):

Object Recognition ◽

Learning And Memory ◽

Water Maze ◽

Recognition Task ◽

Avoidance Task ◽

Novel Object Recognition ◽

Novel Object ◽

Object Recognition Task ◽

Novel Object Recognition Task ◽

The Brain

NBM-T-L-BMX-OS01 (BMX) was derived from the semisynthesis of osthole, isolated fromCnidium monnieri(L.) Cuss., and was identified to be a potent inhibitor of HDAC8. This study shows that HDAC8 is highly expressed in the pancreas and the brain. The function of HDAC8 in the brain has not been adequately studied. Because BMX enhances neurite outgrowth and cAMP response element-binding protein (CREB) activation, the effect of BMX on neural plasticity such as learning and memory is examined. To examine declarative and nondeclarative memory, a water maze, a passive one-way avoidance task, and a novel object recognition task were performed. Results from the water maze revealed that BMX and suberoylanilide-hydroxamic-acid-(SAHA-) treated rats showed shorter escape latency in finding the hidden platform. The BMX-treated animals spent more time in the target quadrant in the probe trial performance. An analysis of the passive one-way avoidance results showed that the BMX-treated animals stayed longer in the illuminated chamber by 1 day and 7 days after footshock. The novel object recognition task revealed that the BMX-treated animals showed a marked increase in the time spent exploring novel objects. Furthermore, BMX ameliorates scopolamine-(Sco-) induced learning and memory impairment in animals, indicating a novel role of BMX in learning and memory.

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