Person: Muñoz Céspedes, Alberto
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First Name
Alberto
Last Name
Muñoz Céspedes
Affiliation
Universidad Complutense de Madrid
Faculty / Institute
Ciencias Biológicas
Department
Biología Celular
Area
Biología Celular
Identifiers
3 results
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Item High levels of 27‑hydroxycholesterol results in synaptic plasticity alterations in the hippocampus(Scientific Reports, 2021) Loera‑Valencia, Raul; Vazquez‑Juarez, Erika; Muñoz Céspedes, Alberto; Gerenu, Gorka; Gómez‑Galán, Marta; Lindskog, Maria; DeFelipe, Javier; Cedazo‑Minguez, Angel; Merino‑Serrais, PaulaAlterations in brain cholesterol homeostasis in midlife are correlated with a higher risk of developing Alzheimer’s disease (AD). However, global cholesterol-lowering therapies have yielded mixed results when it comes to slowing down or preventing cognitive decline in AD. We used the transgenic mouse model Cyp27Tg, with systemically high levels of 27-hydroxycholesterol (27-OH) to examine longterm potentiation (LTP) in the hippocampal CA1 region, combined with dendritic spine reconstruction of CA1 pyramidal neurons to detect morphological and functional synaptic alterations induced by 27-OH high levels. Our results show that elevated 27-OH levels lead to enhanced LTP in the Schafer collateral-CA1 synapses. This increase is correlated with abnormally large dendritic spines in the stratum radiatum. Using immunohistochemistry for synaptopodin (actin-binding protein involved in the recruitment of the spine apparatus), we found a signifcantly higher density of synaptopodinpositive puncta in CA1 in Cyp27Tg mice. We hypothesize that high 27-OH levels alter synaptic potentiation and could lead to dysfunction of fne-tuned processing of information in hippocampal circuits resulting in cognitive impairment. We suggest that these alterations could be detrimental for synaptic function and cognition later in life, representing a potential mechanism by which hypercholesterolemia could lead to alterations in memory function in neurodegenerative diseases.Item Pyramidal cell axon initial segment in Alzheimer´s disease(Scientific Reports, 2022) Antón-Fernández, Alejandro; León-Espinosa, Gonzalo; DeFelipe, Javier; Muñoz Céspedes, AlbertoThe axon initial segment (AIS) is a region of the neuron that is critical for action potential generation as well as for the regulation of neural activity. This specialized structure—characterized by the expression of different types of ion channels as well as adhesion, scaffolding and cytoskeleton proteins—is subjected to morpho-functional plastic changes in length and position upon variations in neural activity or in pathological conditions. In the present study, using immunocytochemistry with the AT8 antibody (phospho-tau S202/T205) and 3D confocal microscopy reconstruction techniques in brain tissue from Alzheimer’s disease patients, we found that around half of the cortical pyramidal neurons with hyperphosphorylated tau showed changes in AIS length and position in comparison with AT8-negative neurons from the same cortical layers. We observed a wide variety of AIS alterations in neurons with hyperphosphorylated tau, although the most common changes were a proximal shift or a lengthening of the AISs. Similar results were found in neocortical tissue from non-demented cases with neurons containing hyperphosphorylated tau. These findings support the notion that the accumulation of phospho-tau is associated with structural alterations of the AIS that are likely to have an impact on normal neuronal activity, which might contribute to neuronal dysfunction in AD.Item Slow-wave activity in the S1HL cortex is contributed by different layer-specific field potential sources during development(Journal of Neuroscience, 2019) Ortuño, Tania; López-Madrona, Victor J.; Makarova, Julia; Tapia-Gonzalez, Silvia; Muñoz Céspedes, Alberto; DeFelipe, Javier; Herreras, ÓscarSpontaneous correlated activity in cortical columns is criticalfor postnatal circuit refinement.We used spatial discriminationtechniques to explore the late maturation of synaptic pathways through the laminar distribution of the field potential (FP) generators underlying spontaneous and evoked activities ofthe S1HL cortex in juvenile (P14 –P16) and adult anesthetized rats. Juveniles exhibit an intermittent FP pattern resembling Up/Down states in adults, but with much reduced power and different laminar distribution. Whereas FPs in active periods are dominated by a layer VI generator in juveniles, in adults a developing multipart generatortakes over, displaying current sinks in middle layers (III–V). The blockade of excitatory transmission in upper and middle layers of adults recovered the juvenile-like FP profiles. In additiontothe layer VI generator, a gamma-specific generator in supragranular layers wasthe same in both age groups.While searching for dynamical coupling among generators in juveniles we found significant cross-correlation in one-half of the tested pairs, whereas excessive coherence hindered their efficient separation in adults. Also, potentials evoked by tactile and electrical stimuli showed different short-latency dipoles between the two age groups, and the juveniles lacked the characteristic long latency UP state currents in middle layers. In addition, the mean firing rate of neurons was lower in juveniles. Thus, cortical FPs originate from different intracolumnar segments as they become active postnatally. We suggest that although some cortical segments are active early postnatally, a functional sensory-motor control relies on a delayed maturation and network integration of synaptic connections in middle layers.