A Novel Short Isoform of Cytosolic PSD-95 Interactor (Cypin) Regulates Neuronal Development

Patel, Mihir V.; Swiatkowski, Przemyslaw; Kwon, Munjin; Rodriguez, Ana R.; Campagno, Keith E.; Firestein, Bonnie L.

doi:10.1007/s12035-017-0849-z

Cited by 11 publications

(14 citation statements)

References 48 publications

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“…Furthermore, none of the compounds affected dendrite length (data not shown). These data suggest that in addition to increasing guanine deaminase activity, only H9 increases dendrites, consistent with our previous data that cypin’s action on increasing dendritic arborization does not depend on guanine deaminase activity 17 .…”

Section: Resultssupporting

confidence: 92%

“…We have published extensively on the role of cypin in promoting dendritogenesis 14-18 ; however, it is unclear what role the guanine deaminase activity plays in this activity 14,17 . Thus, we tested the ability of inhibitor B9 and two cypin activators H9 and G5 to alter dendrite branching in hippocampal neurons.…”

Section: Resultsmentioning

confidence: 99%

“…Cytosolic PSD-95 interactor (cypin) is a molecule that regulates plasticity by increasing dendrite number 14-16 , decreasing dendritic spine density and maturity 17,18 , and increasing the frequency of miniature excitatory postsynaptic currents 17 . At the circuit level, cypin overexpression results in an increase in spike count variability and a more complex distribution of spike waveforms 18 .…”

Section: Introductionmentioning

confidence: 99%

“…Furthermore, overexpression of cypin confers resistance to N-methyl-D-aspartate (NMDA)-induced neuronal death, an in vitro model of secondary injury in TBI. As the major guanine deaminase in the brain 14,15,17,19,20 , Cypin activates the first step of the purine salvage pathway to ultimately produce uric acid, an antioxidant that correlates with reduced damage after TBI 21,22 , stroke 23-25 , and spinal cord injury 26,27 and may decrease the development of neurological disorders, such as Parkinson’s Disease 28,29 . Additionally, cypin activity is important for proper brain development 30,31 as the breakdown of guanine by cypin is necessary for the proper patterning of dendrites and formation of spines 14,15,17 .…”

Section: Introductionmentioning

confidence: 99%

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Cypin: A novel target for traumatic brain injury

Swiatkowski

Sweet

Dickson

et al. 2018

Neurobiology of Disease

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Cytosolic PSD-95 interactor (cypin), the primary guanine deaminase in the brain, plays key roles in shaping neuronal circuits and regulating neuronal survival. Despite this pervasive role in neuronal function, the ability for cypin activity to affect recovery from acute brain injury is unknown. A key barrier in identifying the role of cypin in neurological recovery is the absence of pharmacological tools to manipulate cypin activity in vivo. Here, we use a small molecule screen to identify two activators and one inhibitor of cypin's guanine deaminase activity. The primary screen identified compounds that change the initial rate of guanine deamination using a colorimetric assay, and secondary screens included the ability of the compounds to protect neurons from NMDA-induced injury and NMDA-induced decreases in frequency and amplitude of miniature excitatory postsynaptic currents. Hippocampal neurons pretreated with activators preserved electrophysiological function and survival after NMDA-induced injury in vitro, while pretreatment with the inhibitor did not. The effects of the activators were abolished when cypin was knocked down. Administering either cypin activator directly into the brain one hour after traumatic brain injury significantly reduced fear conditioning deficits 5 days after injury, while delivering the cypin inhibitor did not improve outcome after TBI. Together, these data demonstrate that cypin activation is a novel approach for improving outcome after TBI and may provide a new pathway for reducing the deficits associated with TBI in patients.

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Section: Resultssupporting

confidence: 92%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Cypin: A novel target for traumatic brain injury

Swiatkowski

Sweet

Dickson

et al. 2018

Neurobiology of Disease

Self Cite

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“…Cypin also promotes microtubule polymerization by directly binding to tubulin using a domain with high homology to collapsin response mediator protein (CRMP), another maternal autoantibody target described in autism (127, 159). This CRMP-homology domain and a 9 amino acid zinc-binding domain are required for guanine deaminase activity and for the regulation of dendrite branching and neuronal morphology in cultured hippocampal neurons (159, 160). Dendrite morphogenesis is essential for the communication between neurons and when the regulation of the dendritic arborization is altered, this can lead to abnormal spine density and morphology, synapse loss and aberrant synaptic signaling, resulting in modification of the neural circuitry which can lead to neuropsychiatric disorders (14, 161, 162).…”

Section: Maternal Autoantibodiesmentioning

confidence: 99%

Antigenic Targets of Patient and Maternal Autoantibodies in Autism Spectrum Disorder

2019

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Autism spectrum disorder (ASD) is a neurodevelopmental disorder whose behavioral symptoms become apparent in early childhood. The underlying pathophysiological mechanisms are only partially understood and the clinical manifestations are heterogeneous in nature, which poses a major challenge for diagnosis, prognosis and intervention. In the last years, an important role of a dysregulated immune system in ASD has emerged, but the mechanisms connecting this to a disruption of brain development are still largely unknown. Although ASD is not considered as a typical autoimmune disease, self-reactive antibodies or autoantibodies against a wide variety of targets have been found in a subset of ASD patients. In addition, autoantibodies reactive to fetal brain proteins have also been described in the prenatal stage of neurodevelopment, where they can be transferred from the mother to the fetus by transplacental transport. In this review, we give an extensive overview of the antibodies described in ASD according to their target antigens, their different origins, and timing of exposure during neurodevelopment.

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Autoantibody-associated psychiatric syndromes in children: link to adult psychiatry

et al. 2021

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Studies show that psychiatric symptoms in adults and children are sometimes associated with serum neural autoantibodies. The significance of serum neural autoantibodies associated with psychiatric symptoms in children remains often unclear, but might be relevant for the extent and occurrence of psychiatric disease manifestation in later life, as well as therapy and outcome. For this narrative review, we sought articles listed in PubMed and published between 1988 and 2020 addressing the maternal–fetal transfer of neural autoantibodies and psychiatric disorders associated with serum neural autoantibodies. We identified six major subgroups of psychiatric disorders in children that are associated with serum neural autoantibodies: patients with attentional deficit hyperactivity disorder, autism spectrum disorder, obsessive compulsive disorder, Gilles de la Tourette syndrome, psychosis and catatonia. Furthermore, we summarized study findings from maternal–fetal transfer of Contactin-associated protein-like 2, N-methyl-d-aspartate receptor and fetal brain autoantibodies associated with behavioral effects in animals and humans. We hypothesize that the maternal transfer of serum neuronal autoantibodies during or after birth could result (1) in the ignition of an autoimmune-mediated inflammation having neurodevelopmental consequences for their children (autoimmune-priming-attack hypothesis) and (2) has a potential impact on the later manifestation of psychiatric disorders. Through this narrative review, we propose a diagnostic pathway for the clinical diagnosis of a potentially autoimmune origin of psychiatric symptoms in children while considering recent guidelines.

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A Novel Short Isoform of Cytosolic PSD-95 Interactor (Cypin) Regulates Neuronal Development

Cited by 11 publications

References 48 publications

Cypin: A novel target for traumatic brain injury

Cypin: A novel target for traumatic brain injury

Antigenic Targets of Patient and Maternal Autoantibodies in Autism Spectrum Disorder

Autoantibody-associated psychiatric syndromes in children: link to adult psychiatry

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