Role of Brain Modulators in Neurodevelopment: Focus on Autism Spectrum Disorder and Associated Comorbidities

Abstract

Autism spectrum disorder (ASD) and associated neurodevelopmental disorders share similar pathogenesis and clinical features. Pathophysiological changes in these diseases are rooted in early neuronal stem cells in the uterus. Several genetic and environmental factors potentially perturb neurogenesis and synaptogenesis processes causing incomplete or altered maturation of the brain that precedes the symptomology later in life. In this review, the impact of several endogenous neuromodulators and pharmacological agents on the foetus during pregnancy, manifested on numerous aspects of neurodevelopment is discussed. Within this context, some possible insults that may alter these modulators and therefore alter their role in neurodevelopment are high-lighted. Sometimes, a particular insult could influence several neuromodulator systems as is supported by recent research in the field of ASD and associated disorders. Dopaminergic hy-pothesis prevailed on the table for discussion of the pathogenesis of schizophrenia (SCH), atten-tion-deficit hyperactivity disorder (ADHD) and ASD for a long time. However, recent cumulative evidence suggests otherwise. Indeed, the neuromodulators that are dysregulated in ASD and comorbid disorders are as diverse as the causes and symptoms of this disease. Additionally, these neuromodulators have roles in brain development, further complicating their involvement in comorbidity. This review will survey the current understanding of the neuromodulating systems to serve the pharmacological field during pregnancy and to minimize drug-related insults in pa-tients with ASD and associated comorbidity disorders, e.g., SCH or ADHD.

Human iPSC-derived neurons reveal NMDAR-independent dysfunction following HIV-associated insults

“…Considering HAND and other neurodegenerative conditions are often associated with aging, these more subtle mechanisms may accumulate over time to become major contributors to disease onset and progression. Sub-neurotoxic models can also be useful in neuropsychiatric disorders featuring altered neuronal activity without cell death, and in studies of neurodevelopmental disorders, where affected neurons are not yet synaptically mature ( Habela et al, 2016 ; Sabitha et al, 2021 ; Saad et al, 2022 ). One particular sub-neurotoxic phenotype that is relevant in neurodevelopmental disorders is alterations in spine density and morphology, which would not have been captured via our studies of MAP2 morphology and may underlie some the observed changes in neuronal activity.…”

The use of cannabinoids in the treatment of attention deficit hyperactivity disorder - a review of the latest literature.

“…Przyczyną takiego upośledzenia mogą być mutacje genetyczne bądź urazy środowiskowe, w tym środki farmakologiczne stosowane klinicznie w czasie ciąży. 5 ADHD jest zaliczane do zaburzeń neurorozwojowych, którego etiologia nie została jeszcze dokładnie poznana. 6 Takie zaburzenia w rozwoju ośrodkowego układu nerwowego obejmują upośledzenie kilku układów neuromodulatorów.…”

“…6 Takie zaburzenia w rozwoju ośrodkowego układu nerwowego obejmują upośledzenie kilku układów neuromodulatorów. 5 Dopamina (DA) i noradrenalina (NA), które są syntetyzowane z L-DOPA, odgrywają istotną rolę w skupianiu uwagi i koncentracji, odpowiadają za motywację, czujność oraz zachowania związane z nagrodą. Leki które używa się do leczenia ADHD wpływają zatem zarówno na układ DA, jak i NA 6 .…”

Effect of subchronic exposure to ambient fine and ultrafine particles on rat motor activity and ex vivo striatal dopaminergic transmission

“…However, the autism spectrum disorder is a complex neurodevelopmental condition, and environmental and genetic factors are proposed to contribute to the disorder pathogenesis (Eve et al 2022). Dopamine is involved in neurogenesis, neuronal migration, and synaptogenesis (Saad et al 2022), and perturbations in dopaminergic innervation and transmission have therefore been proposed to participate in the etiology of the autism spectrum disorder. Although in this study animals were exposed to PM in their adult life, changes in dopaminergic transmission in adulthood could also mimic, at least to some extent, behavioral changes originated by altered development of the brain dopaminergic systems.…”