Leptin regulation of hippocampal synaptic function in health and disease

Hamilton, Kirsty; Harvey, Jenni

doi:10.1016/bs.vh.2020.12.006

Cited by 9 publications

(6 citation statements)

References 106 publications

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“…Leptin is transported across the blood–brain barrier (BBB) via a saturable transport system ( Banks, 2004 ) and is a potent modulator of excitatory synaptic transmission at hippocampal CA1 synapses ( Irving and Harvey, 2014 , 2021 ). Consequently, the ability of leptin to regulate excitatory synaptic efficacy at CA1 synapses suggests that leptin is likely to influence cognition processes ( Hamilton and Harvey, 2021 ; Harvey, 2022 ). However, leptin transport across the BBB is impaired in high BMI phenotypes ( Banks et al, 1999 ), which has an adverse effect on the synaptic transmission of hippocampal CA1 ( Grillo et al, 2011 ).…”

Section: Discussionmentioning

confidence: 99%

Body mass index related to executive function and hippocampal subregion volume in subjective cognitive decline

Chen

Cai

et al. 2022

Front. Aging Neurosci.

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ObjectiveThis study aims to explore whether body mass index (BMI) level affects the executive function and hippocampal subregion volume of subjective cognitive decline (SCD).Materials and methodsA total of 111 participants were included in the analysis, including SCD (38 of normal BMI, 27 of overweight and obesity) and normal cognitive control (NC) (29 of normal BMI, 17 of overweight and obesity). All subjects underwent the Chinese version of the Stroop Color-Word Test (SCWT) to measure the executive function and a high-resolution 3D T1 structural image acquisition. Two-way ANOVA was used to examine the differences in executive function and gray matter volume in hippocampal subregions under different BMI levels between the SCD and NC.ResultThe subdimensions of executive function in which different BMI levels interact with SCD and NC include inhibition control function [SCWT C-B reaction time(s): F(1,104) = 5.732, p = 0.018], and the hippocampal subregion volume of CA1 [F(1,99) = 8.607, p = 0.004], hippocampal tail [F(1,99) = 4.077, p = 0.046], and molecular layer [F(1,99) = 6.309, p = 0.014]. After correction by Bonferroni method, the population × BMI interaction only had a significant effect on the CA1 (p = 0.004). Further analysis found that the SCWT C-B reaction time of SCD was significantly longer than NC no matter whether it is at the normal BMI level [F(1,104) = 4.325, p = 0.040] or the high BMI level [F(1,104) = 21.530, p < 0.001], and the inhibitory control function of SCD was worse than that of NC. In the normal BMI group, gray matter volume in the hippocampal subregion (CA1) of SCD was significantly smaller than that of NC [F(1,99) = 4.938, p = 0.029]. For patients with SCD, the high BMI group had worse inhibitory control function [F(1,104) = 13.499, p < 0.001] and greater CA1 volume compared with the normal BMI group [F(1,99) = 7.619, p = 0.007].ConclusionThe BMI level is related to the inhibition control function and the gray matter volume of CA1 subregion in SCD. Overweight seems to increase the gray matter volume of CA1 in the elderly with SCD, but it is not enough to compensate for the damage to executive function caused by the disease. These data provide new insights into the relationship between BMI level and executive function of SCD from the perspective of imaging.

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Section: Discussionmentioning

confidence: 99%

Body mass index related to executive function and hippocampal subregion volume in subjective cognitive decline

Chen

Cai

et al. 2022

Front. Aging Neurosci.

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“…Studies in animal models support the neuroprotective effects of leptin and the administration of exogenous leptin as a possible therapy for AD (Hamilton & Harvey, 2021) (Table 1). Even though there are no clinical trials in humans, a study carried out in congenital cases of leptin deficiency (Paz‐Filho et al, 2015) suggests leptin administration may be a safe treatment.…”

Section: Effects Of Adipokines On the Brain And Cerebrovascular Syste...mentioning

confidence: 98%

Adipose tissue as a therapeutic target for vascular damage in Alzheimer's disease

Bettinetti‐Luque,

Trujillo‐Estrada,

Garcia‐Fuentes

et al. 2023

British J Pharmacology

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The adipose tissue (AT) has recently been recognized as an important endocrine organ that plays a crucial role in energy metabolism and in the immune response in multiple metabolic tissues. With this regard, emerging evidence indicates that an important crosstalk exists between the AT and the brain. However, the AT contribution in the development of age‐related diseases, including Alzheimer’s disease (AD), remains poorly defined. New studies suggest that the AT modulates brain function through multiple bioactive factors known as adipokines, which can cross the blood brain barrier (BBB) to reach the brain target‐areas or even regulate the BBB function. In this review, we discuss the effect of multiple adipokines in the BBB physiology, their contribution to the development of AD and their therapeutic potential.

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“…Sin embargo, el cerebro, que consume mucha energía, no necesita la insulina para absorberla, pero esta hormona llega al cerebro, especialmente al hipocampo, donde se une a receptores específicos y modula mecanismos de plasticidad sináptica subyacentes a los procesos de aprendizaje y memoria [ 46 , 47 ]. La leptina también participa en mecanismos de plasticidad sináptica [ 48 ]. En consecuencia, las alteraciones de la leptina y la insulina no sólo dificultan la regulación de los mecanismos de saciedad en el hipotálamo, sino que también interrumpen mecanismos básicos de formación de la memoria en el hipocampo.…”

Section: Desarrollounclassified

Efectos del sobrepeso y la obesidad en las funciones cognitivas de niños y adolescentes

Nicolovius¹

2022

RevNeurol

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Introducción. Investigaciones recientes sugieren que el sobrepeso y la obesidad en niños y adolescentes afectan a los procesos cognitivos y pueden alterar el aprendizaje escolar. En particular, las denominadas funciones ejecutivas, como la capacidad de inhibición de la respuesta, el control de la impulsividad, la flexibilidad cognitiva, la planificación y la toma de decisiones, se han relacionado de forma inversa con el índice de masa corporal. Objetivo. Este trabajo pretende examinar las hipótesis neurobiológicas y psicológicas que explican por qué el sobrepeso y la obesidad alteran las funciones cognitivas de niños y adolescentes. Desarrollo. Las dietas ricas en grasas y azúcares pueden provocar hiperinsulinemia, dislipidemia, hipertensión, aumento del tejido adiposo abdominal y resistencia a la insulina y a la leptina. Estas alteraciones metabólicas inducen un proceso inflamatorio sistémico periférico que puede afectar a la barrera hematoencefálica y al funcionamiento cerebral de regiones vinculadas a los procesos de atención y de aprendizaje y memoria. Algunos trastornos metabólicos de la madre gestante, la obesidad durante el embarazo y las experiencias traumáticas pre- y posnatales pueden desencadenar cambios en el control de la ingesta de comida en niños y adolescentes e inducir sobrepeso en sus etapas críticas del desarrollo. La obesidad afecta al funcionamiento del hipocampo y produce disminución de la sustancia gris de la corteza prefrontal, modificando con ello las capacidades cognitivas, especialmente las funciones ejecutivas. Conclusiones. El sobrepeso y la obesidad en la infancia y la adolescencia son un factor de riesgo no sólo para la salud general, sino también para el correcto desarrollo cerebral y de las funciones cognitivas, y pueden, por tanto, conducir al fracaso escolar.

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Leptin regulation of hippocampal synaptic function in health and disease

Abstract: One contribution of 35 to a Discussion Meeting Issue 'Synaptic plasticity in health and disease'.

Cited by 9 publications

References 106 publications

Body mass index related to executive function and hippocampal subregion volume in subjective cognitive decline

Body mass index related to executive function and hippocampal subregion volume in subjective cognitive decline

Adipose tissue as a therapeutic target for vascular damage in Alzheimer's disease

Efectos del sobrepeso y la obesidad en las funciones cognitivas de niños y adolescentes

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