fisiopatologia dello stress neonatale
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Il centro del controllo dello stress è l’amigdala, cui fa da supporto l’ippocampo.All’amigdala arrivano segnali nervosi che mostrano un ambiente ostile o sconosciuto e l’amigdala risponde facendo partire risposte ormonali in particolare attivando la produzione di cortisolo
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PVN Nucleo mediale paraventricolare dell’ipotalamo
Regolazione neuroendocrina dello stress: recenti acquisizioni FLAVIO POZZI, GAETANO FRAJESE NÓO ς 3:2004; 143-154
Ma il cortisolo e altri elementi possono tornare ad amigdala e ippocampo danneggiandoli
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Short-term survival of newly generated cells is reduced by stress.
Rosanne M. Thomas et al. J. Neurosci. 2007;27:2734-2743
©2007 by Society for Neuroscience
Short-term survival of newly generated cells is reduced by stress. A , B , Histological evaluation of BrdU-positive cells in animals examined 1 week after the stress episode (Fig. 1 C, experiment 2) revealed a robust population of BrdU-positive cells in the dentate gyrus of control animals ( A ), but an obvious reduction in cell number for intruder rats ( B ). C–F , Higher magnification of the boxed region shows BrdU-positive cells at various focal planes. Some cells present at one focal plane ( C , D , arrows) are not observed at a deeper focal plane when other BrdU-positive cells come into focus ( E , F , arrowheads). The three-dimensional distribution of cells within the section thickness shows the need for stereological quantitation. Scale bars: A , B , 250 μm; C–F , 25 μm.
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Nel neonato l’effetto è simile, ma in più abbiamo due fattiUn’immaturità e fragilità delle cellule nervose dell’intero encefaloUna difficoltà visuale e culturale a riconoscere che il neonato soffre lo stress come e più che un adulto
Gli effetti dello stress sul neonato sono studiati soprattutto su animali.E si riferiscono a studi che mostrano gli effetti sul cervello della sottrazione della mamma; oppure di ripetuti stimoli dolorosi
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• In humans, exposure to childhood abuse or neglect, for example, has been associated with an increased risk of anxiety and mood disorders, obesity, cardiovascular disease and addiction.
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anxiety- and depression-like phenotypes, such as
reduced negative-feedback of the HPA axis
and Neophobia.une addiction pour l’alcool
alterations in arginine
vasopressin (AVP) expression
dépendance à la morphine
by impairments in learning and memory
tasks such as the Morris water maze
and novel object recognition.
increased levels of novelty induced anxiety, indicated by increased startle responses,
decreased exploration in novel environment and
increased latencies to enter a novel environment
2011
2014
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Dorsal Root Gamglion
Rostroventral medulla
Periaqueductal Grey Matter Paraventral Nucleus of Hypothalamus
When the animal reaches adulthood, a decrease in phasic inhibitory signalling is observed, due to a selective reduction in glycine receptor (GlyR)-mediated input to GABAergic and glutamatergic lamina II neurons and a decreased density of tonic GlyR-mediated current in the glutamatergic population (Liet al., 2013)
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Figure 1. Cortical thickness at age 7 years in relation to neonatal pain-related stress adjusted for clinical confounders.
Ranger M, Chau CMY, Garg A, Woodward TS, Beg MF, et al. (2013) Neonatal Pain-Related Stress Predicts Cortical Thickness at Age 7 Years in Children Born Very Preterm. PLoS ONE 8(10): e76702. doi:10.1371/journal.pone.0076702http://journals.plos.org/plosone/article?id=info:doi/10.1371/journal.pone.0076702
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I meccanismi con cui lo stress danneggia il cervello neonatale sono vari:Aumento della pressione del sangue e del liquido cerebraleAumento di produzione di aminoacidi eccitatori e radicali liberiAlterazione dell’espressione di alcuni geni-chiave per l’integrità del cervello, come quello che regola la pressione (gene della vasopressina), la plasticità cerebrale e i recettori del cortisone
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Brain-derived neurotrophic factor)
Marija Kundakovic,Frances A Champagne: Early-Life Experience, Epigenetics, and the Developing Brain. Neuropsychopharmacology REVIEWS (2015) 40, 141–153
Nel cervello, è attivo nell'ippocampo, corteccia cerebrale, e prosencefalobasale - aree vitali per l'apprendimento, la memoria, e il pensiero.
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Marija Kundakovic,Frances A Champagne: Early-Life Experience, Epigenetics, and the Developing Brain. Neuropsychopharmacology REVIEWS (2015) 40, 141–153
The glucocorticoid receptor (GR, or GCR) also known as NR3C1 (nuclear receptor subfamily 3, group C, member 1) is the receptor to which cortisol and other glucocorticoids bind
In rodents, maternal licking and grooming over the first days of life cause reduced HPA-axis reactivity and anxiety-like behaviors mediated via increased GR expression accounted for, at least in part, by demethylation at exon 1–7 promoter of the rat GR gene (Nr3c1) in the hippocampus of the offspring.
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C Murgatroyd. Translational Psychiatry (2015) 5, e560
Child NR3C1 1-F promoter methylation percent by standardized maternal stroking scores. The child’s raw methylation percent decreases with maternal stroking for children with mothers who reported low prenatal but high postnatal depression scores (solid line). No such decrease is seen for the remainder of the children (dashed).
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Creare un ambiente a misura di neonato, con la “care” centrata sul bambino e sulla famiglia (NIDCAP) o riducendo il dolore (es. con la saturazione sensoriale) porta a un miglior sviluppo cerebrale misurato con la risnanza magnetica, con l’eeg e l’esame clinico
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Guzzetta A et al: The Journal of Neuroscience 2009 • 29(18):6042– 6051
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E infants showed a significantly smaller increase than C infants in umWM volumeE infants showed decreased coherence (green arrows), likely representing the pruning of C-group hyper-connectivities
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Attenzione però alle fonti di stress nascosto.Lo stesso parto può essere onte di stress, e dipende dal tipo di parto che il bambino subisce.E non va dimenticato che il primo fattore di rischio di stress per il bambino è avere infermieri e medici stressati…
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