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Investigating the Impact of Early-Li...

Belliveau, Claudia,

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Investigating the Impact of Early-Life Adversity on Perineuronal Nets in the Human Brain /

紀錄類型:	書目-電子資源 : Monograph/item
正題名/作者:	Investigating the Impact of Early-Life Adversity on Perineuronal Nets in the Human Brain // Claudia Belliveau.
作者:	Belliveau, Claudia,
面頁冊數:	1 electronic resource (182 pages)
附註:	Source: Dissertations Abstracts International, Volume: 86-04, Section: B.
Contained By:	Dissertations Abstracts International86-04B.
標題:	Brain-derived neurotrophic factor. -
電子資源:	https://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=31527143
ISBN:	9798342121064

Investigating the Impact of Early-Life Adversity on Perineuronal Nets in the Human Brain /
Belliveau, Claudia,

Investigating the Impact of Early-Life Adversity on Perineuronal Nets in the Human Brain /Claudia Belliveau. - 1 electronic resource (182 pages)

Source: Dissertations Abstracts International, Volume: 86-04, Section: B.

Severe child abuse experienced during the critical period of developmental brain plasticity significantly increases the risk of depression and suicide later in life. Perineuronal nets (PNNs), a condensed form of extracellular matrix (ECM), play a pivotal role in dampening the critical period of plasticity. These nets selectively enwrap specific neurons in the brain through a process that remains inadequately understood. Comprising primarily chondroitin-sulfate (CS) proteoglycans from the lectican family, PNNs consist of CS glycosaminoglycan (GAG) side chains attached to a core protein. CS disaccharides (CS-d) can manifest in various isoforms with distinct sulfation patterns, influencing the function and labeling of PNNs. The aim of this thesis was to investigate the impacts of child abuse on PNNs in the postmortem human brain.We first examined the ventromedial prefrontal cortex (vmPFC), a brain area involved in emotion regulation and impulsivity. Our findings revealed a child-abuse associated increased density and maturity of PNNs in individuals who died by suicide during a depressive episode. Significantly, we implicated oligodendrocyte precursor cells for the first time in the genesis of PNN components-a process also altered by child abuse. We then explored PNN composition using liquid chromatography tandem mass spectrometry (LC-MS/MS) to read the sulfation code across various brain regions and species. Intriguingly, we found that early-life stress (ELS) does not exert a long-lasting impact on PNN composition. Lastly, we implicated a dampened microglia response to the persistent increased density of PNNs, by investigating matrix metalloproteinases (MMPs) and various factors implicated in microglial ECM degradation.In conclusion, the findings presented in this thesis unveil enduring effects of child abuse on cortical PNNs and neuroplasticity in the human vmPFC, with glial cells likely contributing to this phenomenon. We posit that these alterations in PNN development and regulation may underlie heightened vulnerability to psychopathologies and suicide, frequently observed in individuals who have experienced childhood maltreatment.

English

ISBN: 9798342121064Subjects--Topical Terms:

3685829
Brain-derived neurotrophic factor.

Investigating the Impact of Early-Life Adversity on Perineuronal Nets in the Human Brain /
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520 $a Severe child abuse experienced during the critical period of developmental brain plasticity significantly increases the risk of depression and suicide later in life. Perineuronal nets (PNNs), a condensed form of extracellular matrix (ECM), play a pivotal role in dampening the critical period of plasticity. These nets selectively enwrap specific neurons in the brain through a process that remains inadequately understood. Comprising primarily chondroitin-sulfate (CS) proteoglycans from the lectican family, PNNs consist of CS glycosaminoglycan (GAG) side chains attached to a core protein. CS disaccharides (CS-d) can manifest in various isoforms with distinct sulfation patterns, influencing the function and labeling of PNNs. The aim of this thesis was to investigate the impacts of child abuse on PNNs in the postmortem human brain.We first examined the ventromedial prefrontal cortex (vmPFC), a brain area involved in emotion regulation and impulsivity. Our findings revealed a child-abuse associated increased density and maturity of PNNs in individuals who died by suicide during a depressive episode. Significantly, we implicated oligodendrocyte precursor cells for the first time in the genesis of PNN components-a process also altered by child abuse. We then explored PNN composition using liquid chromatography tandem mass spectrometry (LC-MS/MS) to read the sulfation code across various brain regions and species. Intriguingly, we found that early-life stress (ELS) does not exert a long-lasting impact on PNN composition. Lastly, we implicated a dampened microglia response to the persistent increased density of PNNs, by investigating matrix metalloproteinases (MMPs) and various factors implicated in microglial ECM degradation.In conclusion, the findings presented in this thesis unveil enduring effects of child abuse on cortical PNNs and neuroplasticity in the human vmPFC, with glial cells likely contributing to this phenomenon. We posit that these alterations in PNN development and regulation may underlie heightened vulnerability to psychopathologies and suicide, frequently observed in individuals who have experienced childhood maltreatment.
520 $a La maltraitance infantile subie au cours de la periode critique de la plasticite cerebrale augmente considerablement le risque de depression et de suicide plus tard dans la vie. Les filets perineuronaux (FPN), une forme condensee de matrice extracellulaire (MEC), jouent un role essentiel dans l'attenuation de la periode critique de plasticite. Ces filets enveloppent selectivement des neurones specifiques dans le cerveau par un processus qui reste mal compris. Composes principalement de proteoglycanes a base de chondroitine-sulfate (CS) de la famille des lecticans, les FPN sont constitues de chaines laterales de glycosaminoglycanes (GAG) CS attachees a une proteine centrale. Les disaccharides CS (CS-d) peuvent se manifester sous differentes isoformes avec des schemas de sulfatation distincts, influencant la fonction et le marquage des FPN. L'objectif de cette these etait d'etudier les impacts de la maltraitance infantile sur les FPN dans le cerveau humain post-mortem.Nous avons d'abord examine le cortex prefrontal ventromedian (vmPFC), une region cerebrale impliquee dans la regulation des emotions et de l'impulsivite. Nos resultats ont revele une augmentation de la densite et de la maturite des FPN associee a l'abus d'enfants chez les personnes decedees par suicide au cours d'un episode depressif. De plus, nous avons implique pour la premiere fois les cellules precurseurs d'oligodendrocytes dans la genese des composants des FPN, un processus egalement altere par la maltraitance infantile. Nous avons ensuite explore la composition des FPN en utilisant la chromatographie liquide avec spectrometrie de masse en tandem (LC-MS/MS) pour lire le code de sulfatation dans differentes regions du cerveau et chez differentes especes. Nous avons ensuite constate (avec surprise) que le stress au debut de la vie n'exerce pas d'impact durable sur la composition du FPN. Enfin, nous avons mis en evidence une reponse attenuee de la microglie a l'augmentation persistante de la densite des FPN, en etudiant les metalloproteinases matricielles et divers facteurs impliques dans la degradation de la MEC par la microglie.En conclusion, les resultats presentes dans cette these revelent des effets persistants de la maltraitance infantile sur les FPN corticaux et la neuroplasticite au sein du vmPFC humain, les cellules gliales contribuant probablement a ce phenomene. Nous postulons que ces alterations dans le developpement et la regulation des FPN puissent etre a l'origine d'une vulnerabilite accrue aux psychopathologies et au suicide, tous deux plus frequents chez les individus ayant subi de la maltraitance au cours de l'enfance.
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650 4 $a Post traumatic stress disorder. $3 3543866
650 4 $a Suicides & suicide attempts. $3 3556045
650 4 $a Psychopathology. $3 531107
650 4 $a Clinical psychology. $3 524863
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710 2 $a McGill University (Canada). $e degree granting institution. $3 3759190
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