1,721,025 research outputs found
BDNF and its Role in the Alcohol Abuse Initiated During Early Adolescence: Evidence from Preclinical and Clinical Studies
No full textBrain-derived neurotrophic factor (BDNF) is a crucial brain signaling protein that is integral to many signaling pathways. This neurotrophin has shown to be highly involved in brain plastic processes such as neurogenesis, synaptic plasticity, axonal growth, and neurotransmission, among others. In the first part of this review, we revise the role of BDNF in different neuroplastic processes within the central nervous system. On the other hand, its deficiency in key neural circuits is associated with the development of psychiatric disorders, including alcohol abuse disorder. Many people begin to drink alcohol during adolescence, and it seems that changes in BDNF are evident after the adolescent regularly consumes alcohol. Therefore, the second part of this manuscript addresses the involvement of BDNF during adolescent brain maturation and how this process can be negatively affected by alcohol abuse. Finally, we propose different BNDF enhancers, both behavioral and pharmacological, which should be considered in the treatment of problematic alcohol consumption initiated during the adolescence
The role of neural and psychological factors in functional recovery
No full textRecovery from brain insults which look similar at first glance may be a heterogeneous
phenomenon, since injury characteristics and neuropathological correlates
do not completely account for the variance in clinical outcomes, so that
predicting which patients will struggle and which will thrive is a difficult challenge.
The dissimilar behavioural and emotional outcomes often represent the
biggest barrier to rehabilitative treatment both in the acute phase and in social,
professional, and familial reintegration on the long term. Growing data indicate
that among the multiple neurobiological and psychological factors that impact on
the degree of brain recovery (Petrosini, 2017) there are the elements related to
pre-morbid personality and environmental context of the patient
Cerebellum, Embodied Emotions, and Psychological Traits
No full textThis chapter addresses how the embodiment approach may represent a unifying perspective for examining the cerebellar role in emotional behavior and psychological traits. It is not intended to be exhaustive, but rather it can be a good starting point for advancing the cerebellar neural mechanism underlying embodiment. Our goal is to provide illustrative examples of embodied emotions and psychological traits in the emerging field of emotional and cognitive cerebellum. We illustrate how the cerebellum could be an important hub in the embodiment processes, associated with empathic abilities, impaired emotional identification and expression (as occurring for example in the presence of alexithymia), and specific psychological constructs (i.e., hypnotizability).This chapter addresses how the embodiment approach may represent a unifying perspective for examining the cerebellar role in emotional behavior and psychological traits. It is not intended to be exhaustive, but rather it can be a good starting point for advancing the cerebellar neural mechanism underlying embodiment. Our goal is to provide illustrative examples of embodied emotions and psychological traits in the emerging field of emotional and cognitive cerebellum. We illustrate how the cerebellum could be an important hub in the embodiment processes, associated with empathic abilities, impaired emotional identification and expression (as occurring for example in the presence of alexithymia), and specific psychological constructs (i.e., hypnotizability)
Viewing the personality traits through a cerebellar lens. A focus on the constructs of novelty seeking, harm avoidance, and alexithymia
Full text linkThe variance in the range of personality trait expression appears to be linked to structural variance in specific brain regions. In evidencing associations between personality factors and neurobiological measures, it seems evident that the cerebellum has not been up to now thought as having a key role in personality. This paper will review the most recent structural and functional neuroimaging literature that engages the cerebellum in personality traits, as novelty seeking and harm avoidance, and it will discuss the findings in the context of contemporary theories of affective and cognitive cerebellar function. By using region of interest (ROI)- and voxel-based approaches, we recently evidenced that the cerebellar volumes correlate positively with novelty seeking scores and negatively with harm avoidance scores. Subjects who search for new situations as a novelty seeker does (and a harm avoiding does not do) show a different engagement of their cerebellar circuitries in order to rapidly adapt to changing environments. The emerging model of cerebellar functionality may explain how the cerebellar abilities in planning, controlling, and putting into action the behavior are associated to normal or abnormal personality constructs. In this framework, it is worth reporting that increased cerebellar volumes are even associated with high scores in alexithymia, construct of personality characterized by impairment in cognitive, emotional, and affective processing. On such a basis, it seems necessary to go over the traditional cortico-centric view of personality constructs and to address the function of the cerebellar system in sustaining aspects of motivational network that characterizes the different temperamental trait
Cerebellum and personality traits.
No full textPersonality traits are multidimensional traits comprising cognitive, emotional, and behavioral characteristics, and a wide array of cerebral structures mediate individual variability. Differences in personality traits covary with brain morphometry in specific brain regions. A cerebellar role in emotional and affective processing and on personality characteristics has been suggested. In a large sample of healthy subjects of both sexes and differently aged, the macro- and micro-structural variations of the cerebellum were correlated with the scores obtained in the Temperament and Character Inventory (TCI) by Cloninger. Cerebellar volumes were associated positively with Novelty Seeking scores and negatively with Harm Avoidance scores. Given the cerebellar contribution in personality traits and emotional processing, we investigated the cerebellar involvement even in alexithymia, construct of personality characterized by impairment in cognitive, emotional, and affective processing. Interestingly, the subjects with high alexithymic traits had larger volumes in the bilateral Crus 1. The cerebellar substrate for some personality dimensions extends the relationship between personality and brain areas to a structure up to now thought to be involved mainly in motor and cognitive functions, much less in emotional processes and even less in personality individual differences. The enlarged volumes of Crus 1 in novelty seekers and alexithymics support the tendency to action featuring both personality constructs. In fact, Novelty Seeking and alexithymia are rooted in behavior and inescapably have a strong action component, resulting in stronger responses in the structures more focused on action and embodiment, as the cerebellum is
Alzheimer’s disease and depression in the elderly: A trajectory linking gut microbiota and serotonin signaling
No full textThe occurrence of neuropsychiatric symptoms in the elderly is viewed as an early sign of subsequent cognitive deterioration and conversion from mild cognitive impairment to Alzheimer’s disease. The prognosis in terms of both the severity and progression of clinical dementia is generally aggravated by the comorbidity of neuropsychiatric symptoms and decline in cognitive function. Undeniably, aging and in particular unhealthy aging, is a silent “engine of neuropathology” over which multiple changes take place, including drastic alterations of the gut microbial ecosystem. This narrative review evaluates the role of gut microbiota changes as a possible unifying concept through which the comorbidity of neuropsychiatric symptoms and Alzheimer’s disease can be considered. However, since the heterogeneity of neuropsychiatric symptoms, it is improbable to describe the same type of alterations in the bacteria population observed in patients with Alzheimer’s disease, as well as it is improbable that the variety of drugs used to treat neuropsychiatric symptoms might produce changes in gut bacterial diversity similar to that observed in the pathophysiology of Alzheimer’s disease. Depression seems to be another very intriguing exception, as it is one of the most frequent neuropsychiatric symptoms in dementia and a mood disorder frequently associated with brain aging. Antidepressants (i.e., serotonin reuptake inhibitors) or tryptophan dietary supplementation have been shown to reduce Amyloid β-loading, reinstate microbial diversity and reduce the abundance of bacterial taxa dominant in depression and Alzheimer’s disease. This review briefly examines this trajectory by discussing the dysfunction of gut microbiota composition, selected bacterial taxa, and alteration of tryptophan and serotonin metabolism/neurotransmission as overlapping in-common mechanisms involved with depression, Alzheimer’s disease, and unhealthy aging
Neurotoxic effects, mechanisms and outcome of 192 IgG-Saporin Lesions
No full textThe first type-selective anti-neuronal active in vivo immunotoxin is the 192 IgG-saporin. 192 IgG-saporin selectively destroys basal forebrain cholinergic neurons that provide cholinergic input to the hippocampus, entire cortical mantle, amygdala, and olfactory bulb. Immunotoxic lesions by 192 IgG-saporin represent a valid animal model of Alzheimer’s disease, given the degeneration of basal cholinergic system present in this pathology.
The selective lesioning of cholinergic innervation by means of 192 IgG-saporin (injected i.p. or i.c.v.) is able to interfere with experience-dependent plasticity. A number of studies have demonstrated alterations of several structural and biochemical parameters related to neuroplasticity (dendritic spines and branching of pyramidal neurons, adult neurogenesis, levels of neurotrophic factors, neurotransmission, microglia density) in both cortical mantle and hippocampus.
Furthermore, lesions of the cholinergic basal forebrain affect cognitive functions, such as learning, memory and attention, as well as sleep-waking cycle. The effects of selective immunotoxic lesions have been examined in a variety of behavioral paradigms of learning and memory. The general framework has to take into account route of injection (i.c.v. or i.p.), lesion extent, age of lesioning, and kind of behavior analyzed. However, 192 IgG-saporin lesions result in a quite unexpected behavioral picture: in fact, massive cholinergic depletion elicits little or no impairment in spatial and nonspatial learning and memory functions and conversely, deficits in attentional and discriminative abilities
Effects of Palmitoylethanolamide on Neurodegenerative Diseases: A Review from Rodents to Humans
Full text linkPalmitoylethanolamide (PEA) stands out among endogenous lipid mediators for its neuroprotective, anti-inflammatory, and analgesic functions. PEA belonging to the N-acetylanolamine class of phospholipids was first isolated from soy lecithin, egg yolk, and peanut flour. It is currently used for the treatment of different types of neuropathic pain, such as fibromyalgia, osteoarthritis, carpal tunnel syndrome, and many other conditions. The properties of PEA, especially of its micronized or ultra-micronized forms maximizing bioavailability and efficacy, have sparked a series of innovative research to evaluate its possible application as therapeutic agent for neurodegenerative diseases. Neurodegenerative diseases are widespread throughout the world, and although they are numerous and different, they share common patterns of conditions that result from progressive damage to the brain areas involved in mobility, muscle coordination and strength, mood, and cognition. The present review is aimed at illustrating in vitro and in vivo research, as well as human studies, using PEA treatment, alone or in combination with other compounds, in the presence of neurodegeneration. Namely, attention has been paid to the effects of PEA in counteracting neuroinflammatory conditions and in slowing down the progression of diseases, such as Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, Frontotemporal dementia, Amyotrophic Lateral Sclerosis, and Multiple Sclerosis. Literature research demonstrated the efficacy of PEA in addressing the damage typical of major neurodegenerative diseases
From animal to human epigenetics
No full textA rat story: Behavioral epigenetics beginnings
Human neurodevelopment is a dynamic and protracted process. It starts in the pre-natal life,
driven by genetic information, and continues unfolding following region-specific pathways up
to early adulthood (Gogtay et al., 2004; Koenderink & Uylings, 1995; Petanjek et al., 2011). Es
pecially during the pre-natal and early post-natal life, the developing brain depends on and is
sensitive to external inputs that shape its architecture and fine-tune neural connectivity patterns
according to environmental requirements (Branchi & Cirulli, 2014; Fox, Levitt, & Nelson, 2010;
Hensch, 2005; Takesian & Hensch, 2013; Teicher, Samson, Anderson, & Ohashi, 2016). Environ
mental inputs are therefore critical for a normative development. On the other hand, adverse
conditions occurring during sensitive periods for the nervous system maturation can interact
with genetic make-up and bias developmental trajectories toward maladaptive outcomes, as dem
onstrated by increased occurrence of psychopathology and psychiatric conditions following
childhood neglect, maltreatment and abuse (Benjet, Borges, & Medina-Mora, 2010; Bick &
Nelson, 2016; Cohen, Brown, & Smaile, 2001; Green et al., 2010; Kessler et al., 2010;
Widom, 1999).
It has been suggested that modifications of adult brain function and behavior changes induced
by early experiences can be determined by changes in the epigenetic status of specific genes (Bale
et al., 2010; Fraga et al., 2005; Maccari, Krugers, Morley-Fletcher, Szyf, & Brunton, 2014;
Tsankova, Renthal, Kumar, & Nestler, 2007). In fact, epigenetic mechanisms, including DNA
methylation, histone modifications, and non-coding RNAs regulation can be affected by various
extrinsic factors, providing a molecular link between external cues and gene expression (Kang
et al., 2011; Maze et al., 2014; Nord, Pattabiraman, Visel, & Rubenstein, 2015; Shibata,
Gulden, & Sestan, 2015).
Human studies evidence that individuals exposed to adversity in early post-natal life (Romens,
McDonald, Svaren, & Pollak, 2015; Tyrka, Price, Marsit, Walters, & Carpenter, 2012; van der
Knaap et al., 2014), or during pre-natal life (Mulligan, D’Errico, Stees, & Hughes, 2012; Perroud
et al., 2014) exhibit altered methylation of genes involved in hypothalamic-pituitary-adrenal (HPA)
axis functionality, as the NR3C1 gene coding glucocorticoid receptors (GR), a key element for the ho
meostasis of stress response system (Herman et al., 2016; Sapolsky, Meaney, & McEwen, 1985).
In turn, altered NR3C1 methylation levels have been associated to emotional and behavioral problems, externalizing and internalizing symptoms (Cicchetti & Handley, 2017; Dadds, Moul, Hawes, Mendoza
Diaz, & Brennan, 2015; Parade et al., 2016; Perroud et al., 2014; van der Knaap, van Oort, Verhulst,
Oldehinkel, & Riese, 2015). Further, reduced levels of NR3C1 messenger RNA (mRNA) and mRNA
transcripts, as well as increased cytosine methylation of the NR3C1 promoter were found in suicide
victims with a history of childhood abuse compared to suicide victims without childhood trauma
and controls (McGowan et al., 2009).
Finally, longitudinal studies on very preterm infant admitted to neonatal intensive care unit, and
thus subjected to pain-related stress and maternal separation, evidence an altered serotonin transporter
gene (SLC6A4) methylation status, predictive of enhanced socio-emotional stress reactivity and asso
ciated with less-than-optimal score at Personal-Social scale of Griffith Mental Development Scales at
12 months of age (Fumagalli et al., 2018; Montirosso et al., 2016; Provenzi, Guida, &
Montirosso, 2018).
Taken together, these findings corroborate an association between environmental experiences,
epigenetic modifications and behavioral outcomes.
Nevertheless, the cascade of biochemical events through which the environment is embedded in the
individual biology, affecting physiology and behavior remains unclear. In addition, not all individuals
exposed to early life adversity develop health issues, psychopathology or psychiatric disorders
(Collishaw et al., 2007; Yehuda & LeDoux, 2007). Though, the genetic make-up, epigenetic charac
teristics, and risk and protective factors that render individuals differently sensitive to environmental
influences are not yet understood (Belsky et al., 2009; Belsky & Pluess, 2009; Branchi, 2011).
Several aspects hamper the possibility to draw firm conclusions from human studies. Retrospective
designs rely on indirect information about the conditions of the participant, and even when information
is available or directly collected within prospective studies, it is virtually impossible to disentangle the
contribution of multiple factors occurring in pre-natal and post-natal life on specific physiological and
behavioral outcomes.
Moreover, both retrospective and prospective human studies depend on availability and access to
appropriate tissues for epigenetic analysis and are based primarily on saliva, blood and buccal cells
samples. Nonetheless, epigenetic patterns appear to be tissue and gene specific (Forest et al., 2018;
Smith et al., 2015) and there is little consensus on how much changes observed in peripheral tissues
may correlates each other and resemble changes in nervous tissue (Di Sante et al., 2018; Thompson
et al., 2013; Walton et al., 2016).
Animal models have strongly stimulated and complemented human studies (Phillips & Roth,
2019)(Box 1). Indeed, the animal models allow to prospectively manipulate the onset, quality, du
ration and predictability of environmental exposures under controlled conditions and to evaluate im
mediate, long-term and trans-generational consequences on candidate gene expression and behavior.
Laboratory animals can be exposed to aversive or permissive environments at different develop
mental time points and both genomic and non-genomic inheritance can be systematically investigated
(Bohacek & Mansuy, 2015, 2017; Francis, Diorio, Liu, & Meaney, 1999; Jirtle & Skinner, 2007;
Mitchell et al., 2016; Richards, 2006). In addition, since epigenetic reactions are bidirectional and po
tentially reversible (Cervoni & Szyf, 2001; Roth, Denu, & Allis, 2001) the causal relationship between
different epigenetic identities and behavioral outcomes can be addressed in animal models by admin
istering specific molecular compounds able to promote or inhibit epigenetic mechanisms as DNA
methylation (Keller, Doherty, & Roth, 2018, 2019; Weaver et al., 2004, 2005; Weaver, Meaney, &
Szyf, 2006).
Here, we report the contribution of animal studies, in particular, laboratory rats (Rattus norvegicus)
and mice (Mus musculus), to the field of human behavioral epigenetics. The chapter focuses on the role
of maternal environment as one of the most studied vectors in inducing epigenetic modifications and
enduring phenotype in the offspring. In addition, studies on the interplay among genetic polymor
phisms, epigenome and aversive environments in contributing to psychiatric disorders and, as a bright
note, on the effect of the exposure to permissive environment (with attention to environmental enrich
ment) will be reported
Perinatal 192 IgG-Saporin as neuroteratogen
No full textThe immunotoxin 192 IgG-saporin selectively destroys basal forebrain cholinergic neurons that provide cholinergic input to the hippocampus, entire cortical mantle, amygdala, and olfactory bulb. Perinatal immunotoxic lesions by 192 IgG-saporin induce long-lasting cholinergic depletion mimicking a number of developmental disorders reported in humans. The perinatal injection of 192 IgG-saporin induces several brain modifications, which are observed in neocortex and hippocampus at short and long term. These plastic changes involve both structural (alterations in brain volume, neuronal morphology, and neurogenesis) and molecular (modulations of the levels of neurotransmitters and other proteins related to neurodegeneration) levels. Moreover, the perinatal injection of 192 IgG-saporin may interact with the brain plastic capacity to react to other injuries. Perinatal 192 IgG-saporin lesions allowed investigating the role of the basal forebrain cholinergic system in modulating behavioral functions in developing as well as adult rats. After perinatal cholinergic depletion, rats display reduced ultrasonic vocalizations as neonates, learning and exploratory deficits as juveniles, altered discriminative abilities, impulsive and perseverative behaviors, and memory deficits as adults. Overall, these findings underline the importance of cholinergic system integrity for the development of specific structural and functional features
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