Leptin facilitates learning and memory performance and enhances hippocampal CA1 long-term potentiation and CaMK II phosphorylation in rats

Osuga, Yutaka; Hori, Nobuaki; Shiraishi, Takeshi; Fukunaga, Kohji; Takeda, Haruhiko; Tsuji, Michiko; Matsumiya, Teruhiko; Ishibashi, Masaru; Aou, Shuji; Li, X.L.; Kohno, Daisuke; Uramura, Kazuhide; Sougawa, Hiromichi; Yada, Toshihiko; Wayner, M.J.; Sasaki, Kohsuke

doi:10.1016/j.peptides.2006.07.001

Cited by 238 publications

(219 citation statements)

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“…Indeed, the hippocampus expresses large concentrations of leptin receptors 17 and leptin modulates the excitability of hippocampal neurons 18 facilitating learning. 19 There are several reports of volumetric Food stimulation and brain glucose utilization PK Thanos et al Abbreviations: Le, lean; Ob, obese; R, restricted; U, unrestricted. Metabolic activation under baseline conditions (before FS) in the four experimental groups.…”

Section: Discussionmentioning

confidence: 99%

Differences in response to food stimuli in a rat model of obesity: in-vivo assessment of brain glucose metabolism

et al. 2008

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Objective: Food intake is regulated by factors that modulate caloric requirements as well as food's reinforcing properties. In this study, we measured brain glucose utilization to an olfactory stimulus (bacon scent), and we examined the role of food restriction and genetic predisposition to obesity on such brain metabolic activity. Methods: Zucker obese (Ob) and lean (Le) rats were divided into four groups: (1) Ob ad-libitum fed, (2) Ob food restricted (70% of ad libitum), (3) Le ad-libitum fed and (4) Le food restricted. Rats were scanned using m-positron emission tomography and 2-[ 18 F]-fluoro-2-deoxy-D-glucose under two conditions: (1) baseline scan (no stimulation) and (2) challenge scan (food stimulation, FS). Results: FS resulted in deactivation of the right and left hippocampus. Ob rats showed greater changes with FS than Le rats (deactivation of hippocampus and activation of the medial thalamus) and Ob but not Le animals deactivated the frontal cortex and activated the superior colliculus. Access to food resulted in an opposite pattern of metabolic changes to the food stimuli in olfactory nucleus (deactivated in unrestricted and activated in restricted) and in right insular/parietal cortex (activated in unrestricted and deactivated in restricted). In addition, restricted but not unrestricted animals activated the medial thalamus. Conclusions: The greater changes in the Ob rats suggest that leptin modulates the regional brain responses to a familiar food stimulus. Similarly, the differences in the pattern of responses with food restriction suggest that FS is influenced by access to food conditions. The main changes with FS occurred in the hippocampus, a region involved in memory, the insular cortex, a region involved with interoception (perception of internal sensations), the medial thalamus (region involved in alertness) and in regions involved with sensory perception (olfactory bulb, olfactory nucleus, occipital cortex, superior colliculus and parietal cortex), which corroborates their relevance in the perception of food.

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Section: Discussionmentioning

confidence: 99%

Differences in response to food stimuli in a rat model of obesity: in-vivo assessment of brain glucose metabolism

et al. 2008

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“…In accordance with the high levels of leptin receptor expression detected at hippocampal synapses [6], evidence is growing that leptin is a potent modulator of hippocampal excitatory synaptic function [11][12][13][14][15]. Indeed, studies in obese leptin-insensitive rodents (Zucker fa/fa rats; db/db mice) have identified deficits in hippocampal long-term potentiation (LTP) and long-term depression (LTD) as well as spatial memory [16,17].…”

Section: Introductionmentioning

confidence: 96%

Leptin regulation of hippocampal synaptic function in health and disease

Irving

Harvey

2014

Phil. Trans. R. Soc. B

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The endocrine hormone leptin plays a key role in regulating food intake and body weight via its actions in the hypothalamus. However, leptin receptors are highly expressed in many extra-hypothalamic brain regions and evidence is growing that leptin influences many central processes including cognition. Indeed, recent studies indicate that leptin is a potential cognitive enhancer as it markedly facilitates the cellular events underlying hippocampal-dependent learning and memory, including effects on glutamate receptor trafficking, neuronal morphology and activity-dependent synaptic plasticity. However, the ability of leptin to regulate hippocampal synaptic function markedly declines with age and aberrant leptin function has been linked to neurodegenerative disorders such as Alzheimer's disease (AD). Here, we review the evidence supporting a cognitive enhancing role for the hormone leptin and discuss the therapeutic potential of using leptin-based agents to treat AD.

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“…Leptin administered in vitro to hippocampal neurons facilitates neuronal processes that are presumed to underlie hippocampal-dependent memory formation, including long-term potentiation (LTP) (Shanley et al, 2001) and long-term depression (LTD) (Durakoglugil et al, 2005). Systemic leptin administration improves performance in a hippocampal-dependent Morris water maze task in rats (Oomura et al, 2006) that requires learning and remembering the spatial location of an escape platform. Further, direct administration of leptin to the hippocampus improves memory consolidation in mice on tasks that involve remembering the location of an aversive event (ie, foot shock) (Farr et al, 2006).…”

Section: Introductionmentioning

confidence: 99%

Hippocampal Leptin Signaling Reduces Food Intake and Modulates Food-Related Memory Processing

Kanoski

Hayes

Greenwald

et al. 2011

Neuropsychopharmacol

132

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The increase in obesity prevalence highlights the need for a more comprehensive understanding of the neural systems controlling food intake; one that extends beyond food intake driven by metabolic need and considers that driven by higher-order cognitive factors. The hippocampus, a brain structure involved in learning and memory function, has recently been linked with food intake control. Here we examine whether administration of the adiposity hormone leptin to the dorsal and ventral sub-regions of the hippocampus influences food intake and memory for food. Leptin (0.1 mg) delivered bilaterally to the ventral hippocampus suppressed food intake and body weight measured 24 h after administration; a higher dose (0.4 mg) was needed to suppress intake following dorsal hippocampal delivery. Leptin administration to the ventral but not dorsal hippocampus blocked the expression of a conditioned place preference for food and increased the latency to run for food in an operant runway paradigm. Additionally, ventral but not dorsal hippocampal leptin delivery suppressed memory consolidation for the spatial location of food, whereas hippocampal leptin delivery had no effect on memory consolidation in a non-spatial appetitive response paradigm. Collectively these findings indicate that ventral hippocampal leptin signaling contributes to the inhibition of food-related memories elicited by contextual stimuli. To conclude, the results support a role for hippocampal leptin signaling in the control of food intake and food-related memory processing.

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Leptin facilitates learning and memory performance and enhances hippocampal CA1 long-term potentiation and CaMK II phosphorylation in rats

Cited by 238 publications

References 77 publications

Differences in response to food stimuli in a rat model of obesity: in-vivo assessment of brain glucose metabolism

Differences in response to food stimuli in a rat model of obesity: in-vivo assessment of brain glucose metabolism

Leptin regulation of hippocampal synaptic function in health and disease

Hippocampal Leptin Signaling Reduces Food Intake and Modulates Food-Related Memory Processing

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