Cerebellar and Striatal Implications in Autism Spectrum Disorders: From Clinical Observations to Animal Models

Thabault, Mathieu; Turpin, Valentine; Maisterrena, Alexandre; Jaber, Mohamed; Egloff, M.; Galvan, Laurie

doi:10.3390/ijms23042294

Cited by 40 publications

(38 citation statements)

References 205 publications

(307 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Therefore, it comes as no surprise that changes in cerebellar structure and function have been linked to many neurodevelopmental disorders, such as attention deficit-hyperactivity disorder (ADHD) or autism spectrum disorders (ASD) ( Courchesne et al, 2005 ; Fatemi et al, 2012 ; Stoodley, 2016 ). Aberrant Purkinje cell localization has been identified as one of the recurrent findings in autistic patients ( Wang et al, 2014 ; Thabault et al, 2022 ).…”

Section: Discussionmentioning

confidence: 99%

Endoglycan Regulates Purkinje Cell Migration by Balancing Cell-Cell Adhesion

et al. 2022

View full text Add to dashboard Cite

The importance of cell adhesion molecules for the development of the nervous system has been recognized many decades ago. Functional in vitro and in vivo studies demonstrated a role of cell adhesion molecules in cell migration, axon growth and guidance, as well as synaptogenesis. Clearly, cell adhesion molecules have to be more than static glue making cells stick together. During axon guidance, cell adhesion molecules have been shown to act as pathway selectors but also as a means to prevent axons going astray by bundling or fasciculating axons. We identified Endoglycan as a negative regulator of cell-cell adhesion during commissural axon guidance across the midline. The presence of Endoglycan allowed commissural growth cones to smoothly navigate the floor-plate area. In the absence of Endoglycan, axons failed to exit the floor plate and turn rostrally. These observations are in line with the idea of Endoglycan acting as a lubricant, as its presence was important, but it did not matter whether Endoglycan was provided by the growth cone or the floor-plate cells. Here, we expand on these observations by demonstrating a role of Endoglycan during cell migration. In the developing cerebellum, Endoglycan was expressed by Purkinje cells during their migration from the ventricular zone to the periphery. In the absence of Endoglycan, Purkinje cells failed to migrate and, as a consequence, cerebellar morphology was strongly affected. Cerebellar folds failed to form and grow, consistent with earlier observations on a role of Purkinje cells as Shh deliverers to trigger granule cell proliferation.

show abstract

Section: Discussionmentioning

confidence: 99%

Endoglycan Regulates Purkinje Cell Migration by Balancing Cell-Cell Adhesion

et al. 2022

View full text Add to dashboard Cite

show abstract

“…Preclinical translational animal studies play a major role in neuroscience research to understand the roles of neuropeptides, neurohormones, and endogenous biomolecules in the normal function of human life such as cognition, emotion, and social interaction, and in pathological alterations developing into neurological and psychiatric disorders [82][83][84][85][86][87][88][89][90][91][92][93][94][95][96][97]. Various bioactive molecules are synthesized in the Try-KYN metabolic system.…”

Section: Discussionmentioning

confidence: 99%

Memory Enhancement with Kynurenic Acid and its Mechanisms in Neurotransmission

Martos¹,

Tuka²,

Tanaka³

et al. 2022

Preprint

View full text Add to dashboard Cite

Kynurenic acid (KYNA) is an endogenous tryptophan (Trp) metabolite known to possess neuroprotective property. KYNA plays critical roles in nociception, neurodegeneration, and neuroinflammation. A lower level of KYNA is observed in patients with neurodegenerative diseases such as Alzheimer’s and Parkinson’s diseases or psychiatric disorders such as depression and autism spectrum disorders, whereas a higher level of KYNA is associated with the pathogenesis of schizophrenia. Little is known about the optimal concentration for neuroprotection and the threshold for neurotoxicity. In this study the effects of KYNA on memory functions were investigated by passive avoidance test in mice. Six different doses of KYNA were administered intracerebroventricularly to previously trained CFLP mice and they were observed following 24 hours. High doses of KYNA (i.e., 20-40 μg/2 μl) significantly decreased the avoidance latency, whereas a low dose of KYNA (0.5 μg/2 μl) significantly elevated it compared with controls, suggesting that the low dose of KYNA enhanced memory function. Furthermore, six different receptor blockers were applied to reveal the mechanisms underlying the memory enhancement induced by KYNA. The series of tests revealed the possible involvement of the serotonergic, dopaminergic, α and β adrenergic, and opiate systems in the nootropic effect. The study confirmed that a low dose of KYNA improved a memory component of cognitive domain, which was mediated by, at least in part, four systems of neurotransmission in an animal model of learning and memory.

show abstract

“…Animal models of ASD include prenatal exposure to valproate during pregnancy, inbred strains of mice expressing autism traits, and genetical modification targeting autism-related genes (including mtDNA) [ 376 ]. The insertion of mtDNA ND6 gene missense mutation ( ND6 P25L ) exhibits ASD endophenotypes, including autism-like behaviors and electroencephalographic profiles, and correlates with mitochondrial respiration and increased RCS of the brain, suggesting a link to mitochondrial dysfunction [ 377 ].…”

Section: Diseases Linked To Mitochondrial Dysfunctionmentioning

confidence: 99%

Mitochondrial Impairment: A Common Motif in Neuropsychiatric Presentation? The Link to the Tryptophan–Kynurenine Metabolic System

Tanaka

Szabó

Spekker

et al. 2022

Cells

119

View full text Add to dashboard Cite

Nearly half a century has passed since the discovery of cytoplasmic inheritance of human chloramphenicol resistance. The inheritance was then revealed to take place maternally by mitochondrial DNA (mtDNA). Later, a number of mutations in mtDNA were identified as a cause of severe inheritable metabolic diseases with neurological manifestation, and the impairment of mitochondrial functions has been probed in the pathogenesis of a wide range of illnesses including neurodegenerative diseases. Recently, a growing number of preclinical studies have revealed that animal behaviors are influenced by the impairment of mitochondrial functions and possibly by the loss of mitochondrial stress resilience. Indeed, as high as 54% of patients with one of the most common primary mitochondrial diseases, mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS) syndrome, present psychiatric symptoms including cognitive impairment, mood disorder, anxiety, and psychosis. Mitochondria are multifunctional organelles which produce cellular energy and play a major role in other cellular functions including homeostasis, cellular signaling, and gene expression, among others. Mitochondrial functions are observed to be compromised and to become less resilient under continuous stress. Meanwhile, stress and inflammation have been linked to the activation of the tryptophan (Trp)–kynurenine (KYN) metabolic system, which observably contributes to the development of pathological conditions including neurological and psychiatric disorders. This review discusses the functions of mitochondria and the Trp-KYN system, the interaction of the Trp-KYN system with mitochondria, and the current understanding of the involvement of mitochondria and the Trp-KYN system in preclinical and clinical studies of major neurological and psychiatric diseases.

show abstract

Cerebellar and Striatal Implications in Autism Spectrum Disorders: From Clinical Observations to Animal Models

Cited by 40 publications

References 205 publications

Endoglycan Regulates Purkinje Cell Migration by Balancing Cell-Cell Adhesion

Endoglycan Regulates Purkinje Cell Migration by Balancing Cell-Cell Adhesion

Memory Enhancement with Kynurenic Acid and its Mechanisms in Neurotransmission

Mitochondrial Impairment: A Common Motif in Neuropsychiatric Presentation? The Link to the Tryptophan–Kynurenine Metabolic System

Contact Info

Product

Resources

About