Early Inflammation Dysregulates Neuronal Circuit Formation <i>In Vivo</i> via Upregulation of IL-1β

Solek, Cynthia M.; Farooqi, Nasr; Brake, Niklas; Kesner, Philip; Schohl, Anne; Antel, Jack; Ruthazer, Edward S.

doi:10.1523/jneurosci.2159-20.2021

Cited by 7 publications

(3 citation statements)

References 77 publications

(86 reference statements)

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“…Lastly, while there is mixed evidence regarding whether pro-inflammatory cytokines can successfully cross the placenta, [ 51 – 53 ] it is well established that the placenta is capable of its own cytokine production [ 54 – 57 ] where acute and chronic maternal inflammation during pregnancy has been associated with neurodevelopmental disorders [ 58 – 62 ]. This is important since increased levels of neuroinflammation have been linked to morphological changes in the brain in animal models [ 63 , 64 ]. Together, these studies suggest several mechanisms by which prenatal ambient air pollution may impact neurodevelopment in early life.…”

Section: Discussionmentioning

confidence: 99%

Prenatal exposure to ambient air pollution is associated with neurodevelopmental outcomes at 2 years of age

et al. 2023

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Background Higher prenatal ambient air pollution exposure has been associated with impaired neurodevelopment in preschoolers and school-aged children. The purpose of this study was to explore the relationships between prenatal ambient air pollution exposure and neurodevelopment during infancy. Methods This study examined 161 Latino mother-infant pairs from the Southern California Mother’s Milk Study. Exposure assessments included prenatal nitrogen dioxide (NO2) and particulate matter smaller than 2.5 and 10 microns in diameter (PM2.5 and PM10, respectively). The pregnancy period was also examined as three windows, early, mid, and late, which describe the first, middle, and last three months of pregnancy. Infant neurodevelopmental outcomes at 2 years of age were measured using the Bayley-III Scales of Infant and Toddler Development. Multivariable linear models and distributed lag linear models (DLM) were used to examine relationships between prenatal exposures and neurodevelopmental scores, adjusting for socioeconomic status, breastfeeding frequency, time of delivery, pre-pregnancy body mass index, and infant birthweight and sex. Results Higher prenatal exposure to PM10 and PM2.5 was negatively associated with composite cognitive score (β = -2.01 [-3.89, -0.13] and β = -1.97 [-3.83, -0.10], respectively). In addition, higher average prenatal exposure to PM10 was negatively associated with composite motor (β = -2.35 [-3.95, -0.74]), scaled motor (β = -0.77 [-1.30, -0.24]), gross motor (β = -0.37 [-0.70, -0.04]), fine motor (β = -0.40 [-0.71, -0.09]), composite language (β = -1.87 [-3.52, -0.22]), scaled language (β = -0.61 [-1.18, -0.05]) and expressive communication scaled scores (β = -0.36 [-0.66, -0.05]). DLMs showed that higher prenatal air pollution exposure during mid and late pregnancy was inversely associated with motor, cognitive, and communication language scores. Conclusions Higher exposure to air pollutants during pregnancy, particularly in the mid and late prenatal periods, was inversely associated with scaled and composite motor, cognitive, and language scores at 2 years. These results indicate that prenatal ambient air pollution may negatively impact neurodevelopment in early life.

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Section: Discussionmentioning

confidence: 99%

Prenatal exposure to ambient air pollution is associated with neurodevelopmental outcomes at 2 years of age

et al. 2023

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“…Moreover, genes affecting neuronal migration and axonal growth which can disrupt white matter long tract brain connectivity, have been found to be associated with schizophrenia 52,53 . Further, prenatal stress, a risk factor for SZ, as shown in a non-mammalian vertebrate model via maternal immune activation, can in uence circuit formation and normal axonal development 54 .…”

Section: Discussionmentioning

confidence: 99%

The organization of frontostriatal brain wiring in non-affective early psychosis compared with healthy subjects using a novel diffusion imaging fiber cluster analysis

et al. 2023

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BackgroundAlterations in brain connectivity may underlie neuropsychiatric conditions such as schizophrenia. We here assessed the degree of convergence of frontostriatal ber projections in 56 young adult healthy controls (HCs) and 108 matched Early Psychosis-Non-Affective patients (EP-NAs) using our novel ber cluster analysis of whole brain diffusion magnetic resonance imaging tractography. MethodsUsing whole brain tractography and our ber clustering methodology on harmonized diffusion magnetic resonance imaging data from the Human Connectome Project for Early Psychosis we identi ed 17 white matter ber clusters that connect frontal cortex (FC) and caudate (Cd) per hemisphere in each group. To quantify the degree of convergence and, hence, topographical relationship of these ber clusters, we measured the inter-cluster mean distances between the endpoints of the ber clusters at the level of the FC and of the Cd, respectively. ResultsWe found 1) in both groups, bilaterally, a non-linear relationship, yielding convex curves, between FC and Cd distances for FC-Cd connecting ber clusters, driven by a cluster projecting from inferior frontal gyrus; however, in the right hemisphere, the convex curve was more attened in EP-NAs; 2) that cluster pairs in the right (p = 0.03), but not left (p = 0.13), hemisphere were signi cantly more convergent in HCs vs EP-NAs; 3) in both groups, bilaterally, similar clusters projected signi cantly convergently to the Cd; and, 4) a signi cant group by ber cluster pair interaction for 2 right hemisphere ber clusters (numbers 5, 11; p = .00023; p = .00023) originating in selective PFC subregions. ConclusionsIn both groups, we found the FC-Cd wiring pattern deviated from a strictly topographic relationship and that similar clusters projected signi cantly more convergently to the Cd. Interestingly, we also found a signi cantly more convergent pattern of connectivity in HCs in the right hemisphere and that 2 clusters from PFC subregions in the right hemisphere signi cantly differed in their pattern of connectivity between groups.we surmise may subserve functions that bene t from greater circuit integration; and, 3) HCs would show a more convergent FC-caudate connectivity pattern compared to EP-NA subjects. Methods SubjectsThis study was comprised of data from 108 young adult EP-NA subjects and 56 controls from the Human Connectome Project for Early Psychosis (HCP-EP) (MPI: Shenton, Breier). Subjects were recruited from 4

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“…However, IL-1β plays a crucial role in regulating axonal dynamics and neural circuit activity during acute inflammation. IL-1β contributes to the increased axonal dynamics, the enhancement of branch addition rates, branch loss, and the increased number of transient branches [220].…”

Section: The Cerebellar Circuit Dysfunctionmentioning

confidence: 99%

Acute Cerebellar Inflammation and Related Ataxia: Mechanisms and Pathophysiology

Parvez

Ohtsuki

2022

Brain Sciences

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The cerebellum governs motor coordination and motor learning. Infection with external microorganisms, such as viruses, bacteria, and fungi, induces the release and production of inflammatory mediators, which drive acute cerebellar inflammation. The clinical observation of acute cerebellitis is associated with the emergence of cerebellar ataxia. In our animal model of the acute inflammation of the cerebellar cortex, animals did not show any ataxia but hyperexcitability in the cerebellar cortex and depression-like behaviors. In contrast, animal models with neurodegeneration of the cerebellar Purkinje cells and hypoexcitability of the neurons show cerebellar ataxia. The suppression of the Ca2+-activated K+ channels in vivo is associated with a type of ataxia. Therefore, there is a gap in our interpretation between the very early phase of cerebellar inflammation and the emergence of cerebellar ataxia. In this review, we discuss the hypothesized scenario concerning the emergence of cerebellar ataxia. First, compared with genetically induced cerebellar ataxias, we introduce infection and inflammation in the cerebellum via aberrant immunity and glial responses. Especially, we focus on infections with cytomegalovirus, influenza virus, dengue virus, and SARS-CoV-2, potential relevance to mitochondrial DNA, and autoimmunity in infection. Second, we review neurophysiological modulation (intrinsic excitability, excitatory, and inhibitory synaptic transmission) by inflammatory mediators and aberrant immunity. Next, we discuss the cerebellar circuit dysfunction (presumably, via maintaining the homeostatic property). Lastly, we propose the mechanism of the cerebellar ataxia and possible treatments for the ataxia in the cerebellar inflammation.

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Early Inflammation Dysregulates Neuronal Circuit Formation In Vivo via Upregulation of IL-1β

Cited by 7 publications

References 77 publications

Prenatal exposure to ambient air pollution is associated with neurodevelopmental outcomes at 2 years of age

Prenatal exposure to ambient air pollution is associated with neurodevelopmental outcomes at 2 years of age

The organization of frontostriatal brain wiring in non-affective early psychosis compared with healthy subjects using a novel diffusion imaging fiber cluster analysis

Acute Cerebellar Inflammation and Related Ataxia: Mechanisms and Pathophysiology

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