Impairment of long-term potentiation and spatial memory in leptin receptor-deficient rodents

Li, X.-L; Aou, Shuji; Osuga, Yutaka; Hori, Nobuaki; Fukunaga, Kohji; Hori, Tetsuro

doi:10.1016/s0306-4522(02)00162-8

Cited by 400 publications

(348 citation statements)

References 66 publications

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“…Molecular mechanisms implicated in this process include actions that modulate synaptic plasticity. Genetically obese rodents with dysfunctional leptin receptors have impaired hippocampal long-term potentiation (LTP) and long-term depression (LTD), and perform poorly on spatial memory tasks (Gerges et al, 2003;Li et al, 2002). Moreover, direct administration of leptin into the dentate gyrus enhances LTP in rats (Wayner et al, 2004), while direct leptin administration into the CA1 region of the hippocampus improves spatial memory and learning in mice (Farr et al, 2006).…”

Section: Discussionmentioning

confidence: 99%

“…In animal models, leptin facilitates learning, spatial memory and long term potentiation (Li et al, 2002), and has been shown to enhance NMDA receptor function and modulate synaptic plasticity in the hippocampus (Shanley et al, 2001). Recent work by Fewlass et al (2004) reveals that leptin may be linked to Alzheimer's disease (AD) through modulation of Aβ production and clearance.…”

Section: Introductionmentioning

confidence: 99%

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Serum leptin level and cognition in the elderly: Findings from the Health ABC Study

Holden

Lindquist

Tylavsky

et al. 2009

Neurobiology of Aging

204

142

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Leptin is a peptide hormone secreted by adipocytes. It has been shown to modulate production and clearance of amyloid beta (Aβ) in rodent models. We sought to determine if serum leptin was associated with cognitive decline in the elderly.We studied 2871 well-functioning elders, aged 70-79, who were enrolled in a prospective study. Serum leptin concentrations were measured at baseline and analyzed by mean ± 1 SD. Clinically significantly cognitive decline over 4 years was defined as ≥ 5 point drop on the Modified Mini Mental State Exam (3MS).Compared to those in the lower leptin groups, elders in the high leptin group had less cognitive decline, 20.5% vs. 24.7% (OR=0.79 95% CI 0.61-1.02, p=0.07). After adjustment for demographic and clinical variables, including body mass index and total percent body fat, those in the high leptin group had significantly less likelihood of cognitive decline, OR=0.66 (95% CI 0.48-0.91). We conclude that in elderly individuals, higher serum leptin appears to protect against cognitive decline, independent of comorbidites and body fat. HHS Public Access

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Serum leptin level and cognition in the elderly: Findings from the Health ABC Study

Holden

Lindquist

Tylavsky

et al. 2009

Neurobiology of Aging

204

142

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“…The greater response of the hippocampus in the Le U than in the Ob U may possibly reflect the effects of leptin in modulating responses to familiar food stimuli. 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.…”

Section: Discussionmentioning

confidence: 99%

“…32 Indeed, impaired hippocampal functioning in rats has been linked to a reduction in the ability to use information provided by interoceptive energy state signals, an increase in appetitive behavior, food intake, weight gain, as well as heightened general behavioral activity in environments that are strongly associated with food. 32 Leptin receptors in the hippocampus appear to be involved in memory function; 17 direct administration of leptin into the hippocampus facilitates long-term potentiation and improves memory processing in mice. 33 Insulin receptors are also expressed in large concentrations in the hippocampus and are believed to be involved in memory function, possibly through their regulation of glucose transport.…”

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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“…Insulin may affect Aβ degradation via an insulin‐degrading metalloprotease. It has been observed that the decreased activity, low concentrations, and small amounts of mRNA of insulin‐degrading enzyme in brains of patients with AD and knockout mice that lack the enzyme have reduced degradation of Aβ and insulin in brain (Lam & Lu, 2007; Li et al, 2002; Shanley, Irving, & Harvey, 2001). Similarly, insulin resistance is commonly observed in older adults (Barzilai, Huffman, Muzumdar, & Bartke, 2012; Morley, 2008).…”

Section: Lifestyle Associations and Interventions For Aging And Admentioning

confidence: 99%

Aging and Alzheimer’s disease: Comparison and associations from molecular to system level

et al. 2018

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Alzheimer's disease is the most prevalent cause of dementia, which is defined by the combined presence of amyloid and tau, but researchers are gradually moving away from the simple assumption of linear causality proposed by the original amyloid hypothesis. Aging is the main risk factor for Alzheimer's disease that cannot be explained by amyloid hypothesis. To evaluate how aging and Alzheimer's disease are intrinsically interwoven with each other, we review and summarize evidence from molecular, cellular, and system level. In particular, we focus on study designs, treatments, or interventions in Alzheimer's disease that could also be insightful in aging and vice versa.

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Impairment of long-term potentiation and spatial memory in leptin receptor-deficient rodents

Cited by 400 publications

References 66 publications

Serum leptin level and cognition in the elderly: Findings from the Health ABC Study

Serum leptin level and cognition in the elderly: Findings from the Health ABC Study

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

Aging and Alzheimer’s disease: Comparison and associations from molecular to system level

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