Publications by authors named "Maria Carmen Inda"

4 Publications

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The epichaperome is a mediator of toxic hippocampal stress and leads to protein connectivity-based dysfunction.

Nat Commun 2020 01 16;11(1):319. Epub 2020 Jan 16.

Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA.

Optimal functioning of neuronal networks is critical to the complex cognitive processes of memory and executive function that deteriorate in Alzheimer's disease (AD). Here we use cellular and animal models as well as human biospecimens to show that AD-related stressors mediate global disturbances in dynamic intra- and inter-neuronal networks through pathologic rewiring of the chaperome system into epichaperomes. These structures provide the backbone upon which proteome-wide connectivity, and in turn, protein networks become disturbed and ultimately dysfunctional. We introduce the term protein connectivity-based dysfunction (PCBD) to define this mechanism. Among most sensitive to PCBD are pathways with key roles in synaptic plasticity. We show at cellular and target organ levels that network connectivity and functional imbalances revert to normal levels upon epichaperome inhibition. In conclusion, we provide proof-of-principle to propose AD is a PCBDopathy, a disease of proteome-wide connectivity defects mediated by maladaptive epichaperomes.
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http://dx.doi.org/10.1038/s41467-019-14082-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6965647PMC
January 2020

Memory retrieval and the passage of time: from reconsolidation and strengthening to extinction.

J Neurosci 2011 Feb;31(5):1635-43

Department of Neuroscience, Mount Sinai School of Medicine, New York, New York, 10029, USA.

An established memory can be made transiently labile if retrieved or reactivated. Over time, it becomes again resistant to disruption and this process that renders the memory stable is termed reconsolidation. The reasons why a memory becomes labile after retrieval and reconsolidates still remains debated. Here, using inhibitory avoidance learning in rats, we provide evidence that retrievals of a young memory, which are accompanied by its reconsolidation, result in memory strengthening and contribute to its overall consolidation. This function associated to reconsolidation is temporally limited. With the passage of time, the stored memory undergoes important changes, as revealed by the behavioral outcomes of its retrieval. Over time, without explicit retrievals, memory first strengthens and becomes refractory to both retrieval-dependent interference and strengthening. At later times, the same retrievals that lead to reconsolidation of a young memory extinguish an older memory. We conclude that the storage of information is very dynamic and that its temporal evolution regulates behavioral outcomes. These results are important for potential clinical applications.
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http://dx.doi.org/10.1523/JNEUROSCI.4736-10.2011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3069643PMC
February 2011

Double-bouquet cells in the monkey and human cerebral cortex with special reference to areas 17 and 18.

Prog Brain Res 2006 ;154:15-32

Cajal Institute (CSIC), Avenida Dr. Arce 37, 28002-Madrid, Spain.

The detailed microanatomical study of the human cerebral cortex began in 1899 with the experiments of Santiago Ramón y Cajal, who applied the Golgi method to define the structure of the visual, motor, auditory and olfactory cortex. In the first article of this series, he described a special type of interneuron in the visual cortex capable of exerting its influence in the vertical dimension. These neurons are now more commonly referred to as double-bouquet cells (DBCs). The DBCs are readily distinguished owing to their characteristic axons that give rise to tightly interwoven bundles of long, vertically oriented axonal collaterals resembling a horsetail (DBC horsetail). Nevertheless, the most striking characteristic of these neurons is that they are so numerous and regularly distributed that the DBC horsetails form a microcolumnar structure. In addition, DBCs establish hundreds of inhibitory synapses within a very narrow column of cortical tissue. These features have generated considerable interest in DBCs over recent years, principally among those researchers interested in the analysis of cortical circuits. In the present chapter, we shall discuss the morphology, synaptic connections and neurochemical features of DBCs that have been defined through the study of these cells in different cortical areas and species. We will mainly consider the immunocytochemical studies of DBCs that have been carried out in the visual cortex (areas 17 and 18) of human and macaque monkey. We will see that there are important differences in the morphology, number and distribution of DBC horsetails between areas 17 and 18 in the primate. This suggests important differences in the microcolumnar organization between these areas, the functional significance of which awaits detailed correlative physiological and microanatomical studies.
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http://dx.doi.org/10.1016/S0079-6123(06)54002-6DOI Listing
January 2007

Voltage-gated ion channels in the axon initial segment of human cortical pyramidal cells and their relationship with chandelier cells.

Proc Natl Acad Sci U S A 2006 Feb 10;103(8):2920-5. Epub 2006 Feb 10.

Departamento de Biología Celular, Universidad Complutense de Madrid, Jose Antonio Novais 2, 28040 Madrid, Spain.

The axon initial segment (AIS) of pyramidal cells is a critical region for the generation of action potentials and for the control of pyramidal cell activity. Here we show that Na+ and K+ voltage-gated channels, together with other molecules involved in the localization of ion channels, are distributed asymmetrically in the AIS of pyramidal cells situated in the human temporal neocortex. There is a high density of Na+ channels distributed along the length of the AIS together with the associated proteins spectrin betaIV and ankyrin G. In contrast, Kv1.2 channels are associated with the adhesion molecule Caspr2, and they are mostly localized to the distal region of the AIS. In general, the distal region of the AIS is targeted by the GABAergic axon terminals of chandelier cells, whereas the proximal region is innervated, mostly by other types of GABAergic interneurons. We suggest that this molecular segregation and the consequent regional specialization of the GABAergic input to the AIS of pyramidal cells may have important functional implications for the control of pyramidal cell activity.
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http://dx.doi.org/10.1073/pnas.0511197103DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1413846PMC
February 2006