Obesity alters mobility and adult neurogenesis, but not hippocampal dependent learning in ob/ob mice

AbstractsBackgroundObesity has become a severe problem among the world’s population with clearly increasing prevalence over the last decades. Because obesity is associated with several comorbidities (e.g. hypertension or cancer) it constitutes an increasing burden for the health care system. Correlations between obesity and cognition have been studied in humans with ambivalent results. Here, we studied the effects of obesity on hippocampus dependent learning and memory and cell morphology in a mouse model of obesity.MethodsThe body mass of male and female Lep+/+(wt) and Lepob/ob(ob/ob) animals with access to food and water ad libitum was measured between postnatal day 60-200 and animals with clear adiposity (4-6 months) were further analyzed. Adult hippocampal neurogenesis in the dentate gyrus was examined using phosphohistone H3 as a marker for proliferation, doublecortin as a marker for differentiation and caspase3 as a marker for apoptosis. Moreover, the density of dendritic spines on apical and basal dendrites of pyramidal neurons of the cornu ammonis 1 (CA1) were analyzed using Golgi impregnation. In addition, mice were subjected to the open field and Morris water maze test in order to analyze locomotor activity and spatial learning.ResultsThe body weight of ob/ob mice nearly doubled during the first 120 postnatal days. Adult hippocampal neurogenesis was reduced in ob/ob mice due to reduced cell proliferation. Dendritic spine densities in the hippocampal area CA1 were not altered in ob/ob mice. Four to six months old ob/ob mice showed reduced locomotor activity in the open field test but similar performance in the Morris water maze compared to control mice.ConclusionOur data show that alterations in adult neurogenesis in leptin-deficient mice are not associated with an impairment in spatial learning abilities. Moreover, ob/ob mice are inconspicuous in the Morris water maze and do not display altered spine densities in the hippocampus, suggesting that obesity does not have a severe impact upon hippocampal neuronal plasticity and spatial learning.

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Maternal Separation Impairs Mother’s Cognition One Month Beyond The Separation

10.21203/rs.3.rs-216210/v1 ◽

2021 ◽

Author(s):

Sara Joushi ◽

Zahra Taherizadeh ◽

Fatemeh Mohtashami Borzadaran ◽

José Francis-Oliveira ◽

Khadije Esmaeilpour ◽

...

Keyword(s):

Locomotor Activity ◽

Learning And Memory ◽

Open Field ◽

Morris Water Maze ◽

Spatial Learning ◽

Water Maze ◽

Maternal Separation ◽

Stressful Event ◽

Spatial Learning And Memory ◽

Postpartum Stress

Abstract Background: Separation of pups from their dam during the infancy not only has detrimental effects on the pups’ brain but also affects dams’ behavior. Postpartum stress may affect mothers’ cognitive functions. In the present study, by using a 180 min/day maternal separation (MS) paradigm, we assessed anxiety- like behavior (in the elevated plus maze) and locomotor activity (in the open field) of rat dams which experienced separation from postnatal day (PND) 1 until weaning. Since no study has ever investigated MS effects on spatial learning and memory of dams in the Morris water maze, we tried for the first time to clarify whether such separation impairs dam’s performance in the Morris water maze. Methods:We assessed dams’ behavior at three time points; 24 hours, 1 week and 1 month after weaning. Therefore, the six groups consisted of control (CTRL); 24h, 1week and 1month and MS; 24h, 1week and 1month was allocated in this study.Results: Our results revealed that although MS-24h and MS-1week groups had intact locomotor activity, MS-1month group showed less locomotor activity in the open field. Moreover, MS induced anxiety–like behavior was more pronounced in MS-1week and MS-1month dams. Spatial learning and memory was also impaired only in MS-1month dams. Conclusions: We can conclude that MS induces cognitive impairments in dam that may appear not immediately after the separation, but a few weeks after such stressful event.

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An old test for new neurons: refining the Morris water maze to study the functional relevance of adult hippocampal neurogenesis

Frontiers in Neuroscience ◽

10.3389/fnins.2013.00063 ◽

2013 ◽

Vol 7 ◽

Cited By ~ 97

Author(s):

Alexander Garthe ◽

Gerd Kempermann

Keyword(s):

Morris Water Maze ◽

Water Maze ◽

Hippocampal Neurogenesis ◽

Adult Hippocampal Neurogenesis ◽

Functional Relevance

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Paradoxical effects of learning the Morris water maze on adult hippocampal neurogenesis in mice may be explained by a combination of stress and physical activity

Genes Brain & Behavior ◽

10.1111/j.1601-183x.2005.00129.x ◽

2005 ◽

Vol 5 (1) ◽

pp. 29-39 ◽

Cited By ~ 72

Author(s):

D. Ehninger ◽

G. Kempermann

Keyword(s):

Physical Activity ◽

Morris Water Maze ◽

Water Maze ◽

Hippocampal Neurogenesis ◽

Adult Hippocampal Neurogenesis ◽

Paradoxical Effects

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Morris Water Maze and Contextual Fear Conditioning Tasks to Evaluate Cognitive Functions Associated With Adult Hippocampal Neurogenesis

Frontiers in Neuroscience ◽

10.3389/fnins.2021.782947 ◽

2022 ◽

Vol 15 ◽

Author(s):

Karina Hernández-Mercado ◽

Angélica Zepeda

Keyword(s):

Fear Conditioning ◽

Learning And Memory ◽

Morris Water Maze ◽

Water Maze ◽

Hippocampal Neurogenesis ◽

Contextual Fear Conditioning ◽

Adult Hippocampal Neurogenesis ◽

Spatial Learning And Memory ◽

Contextual Fear ◽

Adult Lifespan

New neurons are continuously generated and functionally integrated into the dentate gyrus (DG) network during the adult lifespan of most mammals. The hippocampus is a crucial structure for spatial learning and memory, and the addition of new neurons into the DG circuitry of rodents seems to be a key element for these processes to occur. The Morris water maze (MWM) and contextual fear conditioning (CFC) are among the most commonly used hippocampus-dependent behavioral tasks to study episodic-like learning and memory in rodents. While the functional contribution of adult hippocampal neurogenesis (AHN) through these paradigms has been widely addressed, results have generated controversial findings. In this review, we analyze and discuss possible factors in the experimental methods that could explain the inconsistent results among AHN studies; moreover, we provide specific suggestions for the design of more sensitive protocols to assess AHN-mediated learning and memory functions.

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Obesity Impairs Mobility and Adult Hippocampal Neurogenesis

Journal of Experimental Neuroscience ◽

10.1177/1179069519883580 ◽

2019 ◽

Vol 13 ◽

pp. 117906951988358 ◽

Cited By ~ 4

Author(s):

Alexander Bracke ◽

Grazyna Domanska ◽

Katharina Bracke ◽

Steffen Harzsch ◽

Jens van den Brandt ◽

...

Keyword(s):

Cell Proliferation ◽

Open Field ◽

Dendritic Spine ◽

Water Maze ◽

Brain Volume ◽

Hippocampal Neurogenesis ◽

Adult Hippocampal Neurogenesis ◽

Obese Mice ◽

Phosphohistone H3 ◽

Deficient Mice

Currently, it is controversially discussed whether a relationship between obesity and cognition exists. We here analyzed a mouse model of obesity (leptin-deficient mice) to study the effects of obesity on the morphology of the hippocampus (a brain structure involved in mechanisms related to learning and memory) and on behavior. Mice aged 4 to 6 months were analyzed. At this age, the obese mice have nearly double the body weight as controls, but display smaller brains (brain volume is about 10% smaller) as control animals of the same age. Adult hippocampal neurogenesis, a process that is linked to learning and memory, might be disturbed in the obese mice and contribute to the smaller brain volume. Adult hippocampal neurogenesis was examined using specific markers for cell proliferation (phosphohistone H3), neuronal differentiation (doublecortin), and apoptosis (caspase 3). The number of phosphohistone H3 and doublecortin-positive cells was markedly reduced in leptin-deficient mice, but not the number of apoptotic cells, indicating that adult hippocampal neurogenesis on the level of cell proliferation was affected. In addition, dendritic spine densities of pyramidal neurons in the hippocampal area CA1 were analyzed using Golgi impregnation. However, no significant change in dendritic spine densities was noted in the obese mice. Moreover, the performance of the mice was analyzed in the open field as well as in the Morris water maze. In the open field test, obese mice showed reduced locomotor activity, but in the Morris water maze they showed similar performance compared with control animals.

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CGP 35348, GABABReceptor Antagonist, Has a Potential to Improve Neuromuscular Coordination and Spatial Learning in Albino Mouse following Neonatal Brain Damage

BioMed Research International ◽

10.1155/2014/295215 ◽

2014 ◽

Vol 2014 ◽

pp. 1-7 ◽

Cited By ~ 8

Author(s):

Q. Gillani ◽

M. Ali ◽

F. Iqbal

Keyword(s):

Learning And Memory ◽

Brain Damage ◽

Open Field ◽

Morris Water Maze ◽

Spatial Learning ◽

Water Maze ◽

Morris Water Maze Test ◽

Hypoxia Ischemia ◽

Albino Mice ◽

Cgp 35348

To study the effect of CGP 35348 on learning and memory in albino mice following hypoxia ischemia insult, 10 days old albino mice were subjected to right common carotid artery ligation followed by 8% hypoxia for 25 minutes. Following brain damage, mice were fed on normal rodent diet till they were 13 week old. At this time point, mice were divided into two groups. Group 1 received saline and group 2 intrapertoneally CGP 35348 (1 mg/mL solvent/Kg body weight) for 12 days. A battery of tests used to assess long term neurofunction (Morris water maze, Rota rod and open field) along with brain infarct measurement. Overall CGP 35348 has improved the motor function in male and female albino mice but effects were more pronounced in female albino mice. In open field, CGP 35348 treated female albino mice had demonstrated poor exploratory behavior. During Morris water maze test, gender specific effects were observed as CGP 35348 had improved spatial learning and memory and swimming speed in male albino mice but had no effect in female albino mice following hypoxia ischemia encephalopathy (HIE). We concluded that GABAB receptor antagonists CGP 35348 can be used to improve gender based spatial memory.

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Stress-Related Dysfunction of Adult Hippocampal Neurogenesis—An Attempt for Understanding Resilience?

International Journal of Molecular Sciences ◽

10.3390/ijms22147339 ◽

2021 ◽

Vol 22 (14) ◽

pp. 7339

Author(s):

Julia Leschik ◽

Beat Lutz ◽

Antonietta Gentile

Keyword(s):

Major Depression ◽

Adult Neurogenesis ◽

Current Knowledge ◽

Functional Relation ◽

Hippocampal Neurogenesis ◽

Adult Hippocampal Neurogenesis ◽

Special Focus ◽

Extrinsic Cues ◽

Health And Disease ◽

Newborn Neurons

Newborn neurons in the adult hippocampus are regulated by many intrinsic and extrinsic cues. It is well accepted that elevated glucocorticoid levels lead to downregulation of adult neurogenesis, which this review discusses as one reason why psychiatric diseases, such as major depression, develop after long-term stress exposure. In reverse, adult neurogenesis has been suggested to protect against stress-induced major depression, and hence, could serve as a resilience mechanism. In this review, we will summarize current knowledge about the functional relation of adult neurogenesis and stress in health and disease. A special focus will lie on the mechanisms underlying the cascades of events from prolonged high glucocorticoid concentrations to reduced numbers of newborn neurons. In addition to neurotransmitter and neurotrophic factor dysregulation, these mechanisms include immunomodulatory pathways, as well as microbiota changes influencing the gut-brain axis. Finally, we discuss recent findings delineating the role of adult neurogenesis in stress resilience.

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Intrahippocampal co-administration of nicotine and O-acetyl-L-carnitine prevents the H-89-induced spatial learning deficits in Morris water maze

Journal of Complementary and Integrative Medicine ◽

10.1515/jcim-2021-0035 ◽

2021 ◽

Vol 0 (0) ◽

Author(s):

Mahmoud Hashemzaei ◽

Najmeh Baratzadeh ◽

Iraj Sharamian ◽

Sahar Fanoudi ◽

Mehdi Sanati ◽

...

Keyword(s):

Protein Kinase ◽

Spatial Memory ◽

Morris Water Maze ◽

Spatial Learning ◽

Water Maze ◽

Synergistic Effects ◽

Deionized Water ◽

Learning Deficits ◽

Learning Impairments ◽

Morris Water Maze Task

Abstract Objectives H-89 (a protein kinase AII [PKA II] inhibitor) impairs the spatial memory in the Morris water maze task in rats. In the present study, we aimed to study the protective effects of nicotine and O-acetyl-L-carnitine against H-89-induced spatial memory deficits. Methods Spatial memory impairment was induced by the bilateral intrahippocampal administration of 10 µM H-89 (dissolved in dimethyl sulfoxide, DMSO) to rats. The rats then received bilateral administrations of either nicotine (1 μg/μL, dissolved in saline) or O-acetyl-L-carnitine (100 μM/side, dissolved in deionized water) alone and in combination. Control groups received either saline, deionized water, or DMSO. Results The H-89-treated animals showed significant increases in the time and distance travelled to find hidden platforms, and there was also a significant decrease in the time spent in the target quadrant compared to DMSO-treated animals. Nicotine and O-acetyl-L-carnitine had no significant effects on H-89-induced spatial learning impairments alone, but the bilateral intrahippocampal co-administration of nicotine and O-acetyl-L-carnitine prevented H-89-induced spatial learning deficits and increased the time spent in the target quadrant in comparison with H-89-treated animals. Conclusions Our results indicated the potential synergistic effects of nicotine and O-acetyl-L-carnitine in preventing protein kinase AII inhibitor (H-89)-induced spatial learning impairments.

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