Neonatal seizures induced by pentylenetetrazol or kainic acid disrupt primary cilia growth on developing mouse cortical neurons

Parker, A. J.; Le, Megan M.; Smith, Tyler S.; Hoang-Minh, Lan; Atkinson, Eric W.; Ugartemendia, George; Semple‐Rowland, Susan L.; Coleman, Jason E.; Sarkisian, Matthew R.

doi:10.1016/j.expneurol.2016.05.015

Cited by 16 publications

(13 citation statements)

References 56 publications

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“…their length) in the context of neurological insult (Parker et al, 2016), we finally set out to determine whether pilocarpine-induced seizure or carotid artery occlusion-induced ischemia would acutely affect the number of ciliated neurons or the lengths of neuronal primary cilia.…”

Section: Resultsmentioning

confidence: 99%

“…A recent study found that primary cilia development was sensitive to PTZ or KA-induced seizures in the early postnatal period (Parker et al, 2016). In that investigation, the lengths of primary cilia were disrupted upon seizure induction, with neocortical and hippocampal cilia lengthening, shortening, or exhibiting no change, depending on the specific brain region, the developmental age of the animal, and the seizure induction protocol.…”

Section: Discussionmentioning

confidence: 99%

“…For instance, signals propagated through neuronal primary cilia aid in mounting a reactive glial response after spinal cord injury, and promote neuronal survival in multiple sclerosis (MS)-induced cortical axonal degeneration, via upregulation of ciliary neurotrophic factor (CNTF) (Winter et al, 1995; Albrecht et al, 2002; Fuchs and Schwark, 2004; Dutta et al, 2007). On the other hand, early neonatal seizure activity can induce structural damage by altering the lengths of primary cilia on cortical neurons (Parker et al, 2016). Although such findings implicate the neuronal primary cilium’s involvement in the response or contribution to neurological injury and disease, the global organization of neuronal primary cilia throughout the brain remains unknown, and how this pattern of organization may become grossly or regionally disrupted in the context of brain insults has not been previously studied.…”

Section: Introductionmentioning

confidence: 99%

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The radial organization of neuronal primary cilia is acutely disrupted by seizure and ischemic brain injury

et al. 2017

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BACKGROUND Neuronal primary cilia are sensory organelles that are critically involved in the proper growth, development, and function of the central nervous system (CNS). Recent work also suggests that they signal in the context of CNS injury, and that abnormal ciliary signaling may be implicated in neurological diseases. METHODS We quantified the distribution of neuronal primary cilia alignment throughout the normal adult mouse brain by immunohistochemical staining for the primary cilia marker adenylyl cyclase III (ACIII) and measuring the angles of primary cilia with respect to global and local coordinate planes. We then introduced two different models of acute brain insult—temporal lobe seizure and cerebral ischemia, and re-examined neuronal primary cilia distribution, as well as ciliary lengths and the proportion of neurons harboring cilia. RESULTS Under basal conditions, cortical cilia align themselves radially with respect to the cortical surface, while cilia in the dentate gyrus align themselves radially with respect to the granule cell layer. Cilia of neurons in the striatum and thalamus, by contrast, exhibit a wide distribution of ciliary arrangements. In both cases of acute brain insult, primary cilia alignment was significantly disrupted in a region-specific manner, with areas affected by the insult preferentially disrupted. Further, the two models promoted differential effects on ciliary lengths, while only the ischemia model decreased the proportion of ciliated cells. CONCLUSIONS These findings provide evidence for the regional anatomical organization of neuronal primary cilia in the adult brain and suggest that various brain insults may disrupt this organization.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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The radial organization of neuronal primary cilia is acutely disrupted by seizure and ischemic brain injury

et al. 2017

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“…We identified cilia in both neonatal and adult mouse hearts ( Figures 1A, 1B), as evidenced by staining for acetylated tubulin, a protein enriched along the primary cilium. 21,22 Cilia have been implicated in a wide range of functions during development in mice. 4,23 In this regard, we evaluated whether cilia can be detected at different stages of heart development (E9.5, E10.5, E11.5, E12.5 and E15.5) ( Figure 1C).…”

Section: Primary Cilia Are Present In Mouse Heartmentioning

confidence: 99%

Fibroblast Primary Cilia Are Required for Cardiac Fibrosis

et al. 2019

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BACKGROUND: The primary cilium is a singular cellular structure that extends from the surface of many cell types and plays crucial roles in vertebrate development, including that of the heart. Whereas ciliated cells have been described in developing heart, a role for primary cilia in adult heart has not been reported. This, coupled with the fact that mutations in genes coding for multiple ciliary proteins underlie polycystic kidney disease, a disorder with numerous cardiovascular manifestations, prompted us to identify cells in adult heart harboring a primary cilium and to determine whether primary cilia play a role in disease-related remodeling.

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“…Many animal models of neonatal seizures are derivatives of adult seizure models. This is typical of models where a chemoconvulsant (e.g., kainic acid (KA), pentylenetetrazole (PTZ) or flurothyl) is used to trigger seizures [35][36][37][38]. Direct delivery into the brain of KA, a glutamate receptor agonist, to illicit seizures was first achieved by Ben Ari et al in 1978 [39].…”

Section: Animal Models Of Neonatal Seizuresmentioning

confidence: 99%

Neonatal Seizures and Purinergic Signalling

Méndez¹,

Smith

Engel

2020

IJMS

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Neonatal seizures are one of the most common comorbidities of neonatal encephalopathy, with seizures aggravating acute injury and clinical outcomes. Current treatment can control early life seizures; however, a high level of pharmacoresistance remains among infants, with increasing evidence suggesting current anti-seizure medication potentiating brain damage. This emphasises the need to develop safer therapeutic strategies with a different mechanism of action. The purinergic system, characterised by the use of adenosine triphosphate and its metabolites as signalling molecules, consists of the membrane-bound P1 and P2 purinoreceptors and proteins to modulate extracellular purine nucleotides and nucleoside levels. Targeting this system is proving successful at treating many disorders and diseases of the central nervous system, including epilepsy. Mounting evidence demonstrates that drugs targeting the purinergic system provide both convulsive and anticonvulsive effects. With components of the purinergic signalling system being widely expressed during brain development, emerging evidence suggests that purinergic signalling contributes to neonatal seizures. In this review, we first provide an overview on neonatal seizure pathology and purinergic signalling during brain development. We then describe in detail recent evidence demonstrating a role for purinergic signalling during neonatal seizures and discuss possible purine-based avenues for seizure suppression in neonates.

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Neonatal seizures induced by pentylenetetrazol or kainic acid disrupt primary cilia growth on developing mouse cortical neurons

Cited by 16 publications

References 56 publications

The radial organization of neuronal primary cilia is acutely disrupted by seizure and ischemic brain injury

The radial organization of neuronal primary cilia is acutely disrupted by seizure and ischemic brain injury

Fibroblast Primary Cilia Are Required for Cardiac Fibrosis

Neonatal Seizures and Purinergic Signalling

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