The claustrum is a brain structure that remains shrouded in mystery due to the limited understanding of its cellular structure, neural pathways, functionality and physiological aspects. Significant research has unveiled connections spanning from the claustrum to the entire cortex as well as subcortical areas. This widespread connectivity has led to speculations of its role in integrating information from different brain regions, possibly contributing to processes such as attention, consciousness, learning and memory.
View Article and Find Full Text PDFAutism spectrum disorder (ASD) exhibits a gender bias, with boys more frequently affected than girls. Similarly, in mouse models induced by prenatal exposure to valproic acid (VPA), males typically display reduced sociability, while females are less affected. Although both males and females exhibit VPA effects on neuroinflammatory parameters, these effects are sex-specific.
View Article and Find Full Text PDFIntergenerational transmission of the effects of environmental factors on brain function and behavior can occur through epigenetic mechanisms. Valproic acid (VPA) is an anticonvulsant drug that, when administered during pregnancy, causes various birth defects. The mechanisms of action are largely unclear: VPA can reduce neuronal excitability, but it also inhibits the histone deacetylases, affecting gene expression.
View Article and Find Full Text PDFEnvironmental factors acting on young animals affect neurodevelopmental trajectories and impact adult brain function and behavior. Psychiatric disorders may be caused or worsen by environmental factors, but early interventions can improve performance. Understanding the possible mechanisms acting upon the developing brain could help identify etiological factors of psychiatric disorders and enable advancement of effective therapies.
View Article and Find Full Text PDFMost psychiatric disorders show a sex bias in incidence, symptomatology, and/or response to treatment. Males are more susceptible to neurodevelopmental disorders including autism spectrum disorder and attention-deficit activity disorder, while women are more prone to major depressive disorder and anxiety disorders after puberty. A striking difference between males and females in humans and other mammals is that males undergo a process of brain masculinization due to the early exposure to gonadal hormones.
View Article and Find Full Text PDFAutism spectrum disorder (ASD) is a group of neurodevelopmental disorders with an incidence four times higher in boys than in girls. By analyzing the effect of sex in a mouse model of ASD, we were able to identify immune alterations that could underlie this sex bias. Pregnant mice were injected subcutaneously with 600 mg/kg of valproic acid (VPA) or saline at gestational day 12.
View Article and Find Full Text PDFAutism spectrum disorders (ASDs) are neuropsychiatric diseases characterized by impaired social interaction, communication deficits, and repetitive and stereotyped behaviors. ASD etiology is unknown, and both genetic and environmental causes have been proposed. Different brain structures are believed to play a role in ASD-related behaviors, including medial prefrontal cortex (mPFC), hippocampus, piriform cortex (Pir), basolateral amygdala (BLA) and Cerebellum.
View Article and Find Full Text PDFBackground: Autism spectrum disorder (ASD) is characterized by impaired social interactions and repetitive patterns of behavior. Symptoms appear in early life and persist throughout adulthood. Early social stimulation can help reverse some of the symptoms, but the biological mechanisms of these therapies are unknown.
View Article and Find Full Text PDFSemin Cell Dev Biol
May 2018
Perinatal environment plays a crucial role in brain development and determines its function through life. Epidemiological studies and clinical reports link perinatal exposure to infection and/or immune activation to various psychiatric disorders. In addition, accumulating evidence from animal models shows that perinatal inflammation can affect various behaviors relevant to psychiatric disorders such as schizophrenia, autism, anxiety and depression.
View Article and Find Full Text PDFTemporal processing in the seconds-to-minutes range, known as interval timing, is a crucial cognitive function that requires activation of cortico-striatal circuits via dopaminergic-glutamatergic pathways. In humans, both children and adults with autism spectrum disorders (ASD) present alterations in their estimation of time intervals. At present, there are no records of interval timing studies in animal models of ASD.
View Article and Find Full Text PDFDuring an infection, animals suffer several changes in their normal physiology and behavior which may include lethargy, appetite loss, and reduction in grooming and general movements. This set of alterations is known as sickness behavior and although it has been extensively believed to be orchestrated primarily by the immune system, a relevant role for the central nervous system has also been established. The aim of the present work is to develop a simple animal model to allow studying how the immune and the nervous systems interact coordinately during an infection.
View Article and Find Full Text PDFIn Autism Spectrum Disorders (ASD), a bias to a higher incidence in boys than in girls has been reported. With the aim to identify biological mechanisms acting in female animals that could underlie this bias, we used an extensively validated mouse model of ASD: the prenatal exposure to valproic acid (VPA). We found postnatal behavioral alterations in female VPA pups: a longer latency in righting reflex at postnatal day (P) 3, and a delay in the acquisition of the acoustic startle response.
View Article and Find Full Text PDFIncreasing clinical and experimental evidence links immune and inflammatory alterations with the pathogenesis of autism spectrum disorders (ASD). Autistic individuals show signs of neuroinflammation, altered inflammatory responses, and immune abnormalities throughout life. Mice injected subcutaneously with 600 mg/kg valproic acid (VPA600) at gestational day 12.
View Article and Find Full Text PDFPeripheral inflammation, both during the prenatal period and in adulthood, impairs adult neurogenesis. We hypothesized that, similar to other programming effects of prenatal treatments, only prenatal inflammation causes long-term consequences in adult neurogenesis and its neurogenic niche. To test this, pregnant Wistar rats were subcutaneously injected with lipopolysaccharide (LPS; 0.
View Article and Find Full Text PDFRecent reports have given a central role to environmental factors in the etiology of autism spectrum disorders (ASD). However, most proposed perinatal factors seem to converge into the activation of the immune system, suggesting that an early inflammatory response could be a unifying factor in the etiology ASD. Here I review the evidence of early immune activation in individuals with ASD, and the chronic peripheral and central alterations observed in the inflammatory response in ASD.
View Article and Find Full Text PDFBrain Behav Immun
November 2011
TGF-β1 is an anti-inflammatory cytokine that is augmented in the brain of autistic patients and that can affect brain development. In this work, we studied the effects of overexpressing TGF-β1 in the dentate gyrus of adult or young mice on behavior. TGF-β1 overexpression during postnatal development led to a long-term decrease in social interaction and to long-term increases in self-grooming and depression-related behaviors.
View Article and Find Full Text PDFPrenatal exposure to inflammatory stimuli is known to influence adult brain function. In addition, adult hippocampal neurogenesis is impaired by a local pro-inflammatory microenvironment. On this basis, we hypothesized that a pro-inflammatory insult during gestation would have negative effects on adult neurogenesis in the offspring.
View Article and Find Full Text PDFThe perinatal development of the nervous system is influenced by different external and internal stimuli. Previous data show that maternal care and perinatal inflammation can induce long-term changes in anxiety- and depression-related behavior. Our hypothesis is that both maternal care and perinatal inflammation act through interacting biological pathways to program adult behavior.
View Article and Find Full Text PDFThe differentiation of neural stem cells toward a neuronal phenotype is determined by the extracellular and intracellular factors that form the neurogenic niche. In this review, we discuss the available data on the functional role of inflammation and in particular, pro- and anti-inflammatory cytokines, on neuronal differentiation from endogenous and transplanted neural stem/progenitor cells. In addition, we discuss the role of microglial cell activation on these processes and the fact that microglial cell activation is not univocally associated with a pro-inflammatory milieu.
View Article and Find Full Text PDFDuring development, when inhibitory and excitatory synapses are formed and refined, homeostatic mechanisms act to adjust inhibitory input in order to maintain neural activity within a normal range. As the brain matures, synaptogenesis slows and a relatively stable level of inhibition is achieved. Deficits in inhibitory neurotransmission are associated with increased anxiety-related behavior and drugs that potentiate GABA function, the major inhibitory neurotransmitter in the brain, are effective anxiolytics.
View Article and Find Full Text PDFIn humans, anxiety is accompanied by changes in autonomic nervous system function, including increased heart rate, body temperature, and blood pressure, and decreased heart rate variability. In rodents, anxiety is inferred by examining anxiety-related behavioral responses such as avoidance and freezing, and more infrequently by assessing autonomic responses to anxiogenic stimuli. However, few studies have simultaneously measured behavioral and autonomic responses to aversive stimuli in rodents and it remains unclear whether autonomic measures are reliable correlates of anxiety-related behavior in these animal models.
View Article and Find Full Text PDFThe functional role of the long-lasting inflammation found in the substantia nigra (SN) of Parkinson's disease (PD) patients and animal models is unclear. Proinflammatory cytokines such as interleukin-1beta (IL-1beta) could be involved in mediating neuronal demise. However, it is unknown whether the chronic expression of cytokines such as IL-1beta in the SN can alter neuronal vitality.
View Article and Find Full Text PDFAn appropriate inflammatory response is crucial for the maintenance of tissue homeostasis. The inflammatory responses seen in the brain parenchyma differ from those elicited in the periphery, ventricles and meninges. However, although an inflammatory component has been associated with many CNS diseases, the differences among parenchymal inflammatory responses in different brain regions have not yet been fully elucidated.
View Article and Find Full Text PDFInterleukin-1beta (IL-1) expression is associated with a spectrum of neuroinflammatory processes related to chronic neurodegenerative diseases. The single-bolus microinjection of IL-1 into the central nervous system (CNS) parenchyma gives rise to delayed and localized neutrophil recruitment, transient blood-brain barrier (BBB) breakdown, but no overt damage to CNS integrity. However, acute microinjections of IL-1 do not mimic the chronic IL-1 expression, which is a feature of many CNS diseases.
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