Structural and Functional Deviations of the Hippocampus in Schizophrenia and Schizophrenia Animal Models

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(10), P. 5482 - 5482

Published: May 13, 2022

Schizophrenia is a grave neuropsychiatric disease which frequently onsets between the end of adolescence and beginning adulthood. It characterized by variety abnormalities are categorized into positive, negative cognitive symptoms. Most therapeutical strategies address positive symptoms antagonizing D2-dopamine-receptors (DR). However, persist highly impair life quality patients due to their disabling effects. Interestingly, hippocampal deviations hallmark schizophrenia can be observed in early as well advanced phases progression. These alterations commonly accompanied rise neuronal activity. Therefore, formation plays an important role manifestation schizophrenia. Furthermore, studies with animal models revealed link environmental risk factors morphological electrophysiological hippocampus. Here, we review recent findings on structural functional schizophrenic models, give overview current experimental approaches that especially target A better understanding aberrations might clarify impact outcome this severe disease.

Language: Английский

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Perineuronal Nets: Subtle Structures with Large Implications

The Neuroscientist, Journal Year: 2022, Volume and Issue: 29(5), P. 569 - 590

Published: July 23, 2022

Perineuronal nets (PNNs) are specialized structures of the extracellular matrix that surround soma and proximal dendrites certain neurons in central nervous system, particularly parvalbumin-expressing interneurons. Their appearance overlaps maturation neuronal circuits closure critical periods different regions brain, setting their connectivity abruptly reducing plasticity. As a consequence, digestion PNNs, as well removal or manipulation components, leads to boost this plasticity can play key role functional recovery from insults etiopathology neurologic psychiatric disorders. Here we review structure, composition, distribution PNNs variation throughout evolutive scale. We also discuss methodological approaches study these structures. The function during neurodevelopment adulthood is discussed, influence intrinsic extrinsic factors on matrix. Finally, current data alterations described diseases system (CNS), focusing Together, all available point promising target understand physiology pathologic conditions CNS.

Language: Английский

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How Stress Influences the Dynamic Plasticity of the Brain’s Extracellular Matrix

Frontiers in Cellular Neuroscience, Journal Year: 2022, Volume and Issue: 15

Published: Jan. 25, 2022

Diffuse and structured extracellular matrix (ECM) comprise ∼20% of the brain’s volume play important roles in development adult plasticity. Perineuronal nets (PNNs), specialized ECM structures that surround certain types neurons brain, emerge during postnatal period, making their maintenance potentially sensitive to experience. Recent studies have shown stress affects diffuse as well PNNs, such effects are dependent on life stage brain region. Given participates synaptic plasticity, generation neuronal oscillations, synchronous firing across regions, all which been linked cognition emotional regulation, components may be candidate therapeutic targets for stress-induced neuropsychiatric disease. This review considers influence over with a focus functional outcomes potential translational relevance.

Language: Английский

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Perineuronal Nets Alterations Contribute to Stress-Induced Anxiety-Like Behavior

Molecular Neurobiology, Journal Year: 2023, Volume and Issue: 61(1), P. 411 - 422

Published: Aug. 24, 2023

Language: Английский

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Developmental and adult stress: effects of steroids and neurosteroids

Stress, Journal Year: 2024, Volume and Issue: 27(1)

Published: April 2, 2024

In humans, exposure to early life adversity has profound implications for susceptibility developing neuropsychiatric disorders later in life. Studies rodents have shown that stress experienced during postnatal can lasting effects on brain development. Glucocorticoids and sex steroids are produced endocrine glands the from cholesterol; these molecules bind nuclear membrane-associated steroid receptors. Unlike other also be made brain, neurosteroids specifically neurotransmitter receptors, not The relationships among steroids, neurosteroids, multifaceted yet fully understood. However, studies demonstrating altered levels of progestogens, androgens, estrogens, glucocorticoids, their neuroactive metabolites both developmental adult paradigms strongly suggest may important players circuits behavior. this review, we discuss influence various components including neurons, glia, perineuronal nets, with a focus neurosteroids. Gaining an enhanced understanding how impacts intricate systems neurosteroid regulation could prove instrumental identifying novel therapeutic targets stress-related conditions.

Language: Английский

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Impact of stress on inhibitory neuronal circuits, our tribute to Bruce McEwen

Neurobiology of Stress, Journal Year: 2022, Volume and Issue: 19, P. 100460 - 100460

Published: May 13, 2022

This manuscript is dedicated to the memory of Bruce S. McEwen, commemorate impact he had on how we understand stress and neuronal plasticity, profound influence exerted our scientific careers. The focus this review stressors inhibitory circuits, particularly those limbic system, but also consider other regions affected by these adverse experiences. We revise effects acute chronic during different stages development lifespan, taking into account sex animals. first physiology neurons expression molecules related directly GABAergic neurotransmission, then specific interneuron subpopulations, parvalbumin somatostatin expressing cells. Then analyze structures plasticity neurons: polysialylated form neural cell adhesion molecule perineuronal nets. Finally, potential antidepressants or environmental manipulations revert circuits.

Language: Английский

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Early life adversity across different cell- types in the brain

Neuroscience & Biobehavioral Reviews, Journal Year: 2023, Volume and Issue: 148, P. 105113 - 105113

Published: Feb. 28, 2023

Language: Английский

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GABAergic and inflammatory changes in the frontal cortex following neonatal PCP plus isolation rearing, as a dual-hit neurodevelopmental model for schizophrenia

Molecular Neurobiology, Journal Year: 2024, Volume and Issue: 61(9), P. 6968 - 6983

Published: Feb. 16, 2024

Abstract The pathogenesis of schizophrenia begins in early neurodevelopment and leads to excitatory-inhibitory imbalance. It is therefore essential that preclinical models used understand disease, select drug targets evaluate novel therapeutics encompass similar neurochemical deficits. One approach improved modelling incorporates dual-hit neurodevelopmental insults, like neonatal administration phencyclidine (PCP, disrupt development glutamatergic circuitry) then post-weaning isolation (Iso, mimic adolescent social stress). We recently showed male Lister-hooded rats exposed PCP-Iso exhibit reduced hippocampal expression the GABA interneuron marker calbindin. current study expanded on this by investigating changes additional populations GABAergic interneurons frontal cortical tissue from same animals (by immunohistochemistry) as well levels itself (via ELISA). Because inflammatory are also implicated schizophrenia, we performed immunohistochemical evaluations Iba-1 positive microglia ELISA analysis IL-6 brain regions. Single-hit isolation-reared both parvalbumin immunoreactivity prelimbic/infralimbic region cortex. However, was more widespread PCP-Iso, extending medial/ventral lateral/dorsolateral orbitofrontal cortices. Loss markers accompanied increased microglial activation cortices together with elevations not seen following single-hit rearing. These findings enhance face validity advocate use model for future evaluation therapeutics—especially those designed normalise imbalance or reduce neuroinflammation.

Language: Английский

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Degradation of Perineuronal Nets in the Ventral Hippocampus of Adult Rats Recreates an Adolescent-Like Phenotype of Stress Susceptibility

Biological Psychiatry Global Open Science, Journal Year: 2024, Volume and Issue: 4(5), P. 100338 - 100338

Published: June 1, 2024

Psychiatric disorders often emerge during late adolescence/early adulthood, a period with increased susceptibility to socio-environmental factors and coinciding the incomplete parvalbumin interneuron (PVI) development. Stress this causes functional loss of PVIs in ventral hippocampus (vHip), which has been associated dopamine system overdrive. This vulnerability persists until appearance perineuronal nets (PNNs) around PVIs. We assessed long-lasting effects adolescent or adult stress on behavior, tegmental area (VTA) neuron activity, number their PNNs vHip. Additionally, we tested whether PNN removal vHip rats, proposed reset juvenile-like state, recreates an adolescent-like phenotype susceptibility. Male rats underwent 10-day protocol adolescence adulthood. Three four weeks post-stress, evaluated behaviors related anxiety, sociability, cognition, VTA PV+ PNN+ cells Furthermore, animals received intra-vHip infusion chondroitinase ABC (ChABC) degrade before undergoing stress. Unlike stress, induced anxiety responses, reduced cognitive deficits, overdrive, decreased However, ChABC caused produce changes similar those observed after Our findings underscore as heightened impact highlight protective role against stress-induced damage

Language: Английский

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Introduction: What Are Dendritic Spines?

Advances in neurobiology, Journal Year: 2023, Volume and Issue: unknown, P. 1 - 68

Published: Jan. 1, 2023

Language: Английский

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