Publications by authors named "Martinez-Rachadell L"

Pleiotropic actions of insulin and insulin-like growth factor I (IGF-I) in the brain are context- and cell-dependent, but whether this holds for their receptors (insulin receptor (IR) and IGF-I receptor (IGF-IR), respectively), is less clear. We compared mice lacking IR or IGF-IR in glial fibrillary astrocytic protein (GFAP)-expressing astrocytes in a tamoxifen-regulated manner, to clarify their role in this type of glial cells, as the majority of data of their actions in brain have been obtained in neurons. We observed that mice lacking IR in GFAP astrocytes (GFAP IR KO mice) develop mood disturbances and maintained intact cognition, while at the same time show greater pathology when cross-bred with APP/PS1 mice, a model of familial Alzheimer´s disease (AD).

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Article Synopsis
  • Mice lacking insulin receptors in astrocytes exhibit reduced sensitivity to insulin and impaired brain glucose uptake, leading to mitochondrial dysfunction.
  • The absence of insulin receptors causes a disconnect between brain blood flow and glucose uptake, as these mice also produce higher reactive oxidant species (ROS).
  • Treatment with the antioxidant N-acetylcysteine (NAC) improves both ROS levels and neurovascular coupling, revealing insulin receptors' crucial role in regulating glucose uptake and blood vessel growth in the brain.
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Sleep disturbances are common during aging. Compared to young animals, old mice show altered sleep structure, with changes in both slow and fast electrocorticographic (ECoG) activity and fewer transitions between sleep and wake stages. Insulin-like growth factor I (IGF-I), which is involved in adaptive changes during aging, was previously shown to increase ECoG activity in young mice and monkeys.

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It is known that aging is frequently accompanied by a decline in cognition. Furthermore, aging is associated with lower serum IGF-I levels that may contribute to this deterioration. We studied the effect of IGF-I in neurons of the horizontal diagonal band of Broca (HDB) of young (≤6 months old) and old (≥20-month-old) mice to determine if changes in the response of these neurons to IGF-I occur along with aging.

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Insulin-like growth factor-I (IGF-I) signaling plays a key role in learning and memory processes. While the effects of IGF-I on neurons have been studied extensively, the involvement of astrocytes in IGF-I signaling and the consequences on synaptic plasticity and animal behavior remain unknown. We have found that IGF-I induces long-term potentiation (LTP) of the postsynaptic potentials that is caused by a long-term depression of inhibitory synaptic transmission in mice.

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Obesity is a risk factor for Alzheimer's disease (AD), but underlying mechanisms are not clear. We analyzed peripheral clearance of amyloid β (Aβ) in overweight mice because its systemic elimination may impact brain Aβ load, a major landmark of AD pathology. We also analyzed whether circulating insulin-like growth factor I (IGF-I) intervenes in the effects of overweight as this growth factor modulates brain Aβ clearance and is increased in the serum of overweight mice.

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Although sleep disturbances are common co-morbidities of metabolic diseases, the underlying processes linking both are not yet fully defined. Changes in the duration of sleep are paralleled by changes in the levels of insulin-like growth factor-I (IGF-I), an anabolic hormone that shows a circadian pattern in the circulation and activity-dependent entrance in the brain. However, the specific role, if any, of IGF-I in this universal homeostatic process remains poorly understood.

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Insulin (IR) and insulin-like growth factor I (IGF-IR) receptors share structural homology and can form hybrid heterodimers. While different observations suggest that hybrid receptors are important in physiology and pathology, little is known about their function in the brain. To gain further insight into the role of IR/IGF-IR hybrids in this organ, we analyzed their cellular distribution in the mouse brain.

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