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Glial cells are functionally impaired in juvenile neuronal ceroid lipofuscinosis and detrimental to neurons.

Parviainen, Lotta; Dihanich, Sybille; Anderson, Greg W; Wong, Andrew M; Brooks, Helen R; Abeti, Rosella; Rezaie, Payam; Lalli, Giovanna; Pope, Simon; Heales, Simon J; Mitchison, Hannah M; Williams, Brenda P and Cooper, Jonathan D (2017). Glial cells are functionally impaired in juvenile neuronal ceroid lipofuscinosis and detrimental to neurons. Acta neuropathologica communications, 5(1) p. 74.

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DOI (Digital Object Identifier) Link: https://doi.org/10.1186/s40478-017-0476-y
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Abstract

The neuronal ceroid lipofuscinoses (NCLs or Batten disease) are a group of inherited, fatal neurodegenerative disorders of childhood. In these disorders, glial (microglial and astrocyte) activation typically occurs early in disease progression and predicts where neuron loss subsequently occurs. We have found that in the most common juvenile form of NCL (CLN3 disease or JNCL) this glial response is less pronounced in both mouse models and human autopsy material, with the morphological transformation of both astrocytes and microglia severely attenuated or delayed. To investigate their properties, we isolated glia and neurons from Cln3-deficient mice and studied their basic biology in culture. Upon stimulation, both Cln3-deficient astrocytes and microglia also showed an attenuated ability to transform morphologically, and an altered protein secretion profile. These defects were more pronounced in astrocytes, including the reduced secretion of a range of neuroprotective factors, mitogens, chemokines and cytokines, in addition to impaired calcium signalling and glutamate clearance. Cln3-deficient neurons also displayed an abnormal organization of their neurites. Most importantly, using a co-culture system, Cln3-deficient astrocytes and microglia had a negative impact on the survival and morphology of both Cln3-deficient and wildtype neurons, but these effects were largely reversed by growing mutant neurons with healthy glia. These data provide evidence that CLN3 disease astrocytes are functionally compromised. Together with microglia, they may play an active role in neuron loss in this disorder and can be considered as potential targets for therapeutic interventions.

Item Type: Journal Item
ISSN: 2051-5960
Extra Information: ** From Europe PMC via Jisc Publications Router.
** Licence for this article: cc by
Keywords: Neuronal Ceroid Lipofuscinosis, Juvenile Batten Disease, Neuron-glial Interactions, Cln3 Disease, Astrocyte And Microglial Dysfunction
Academic Unit/School: Faculty of Science, Technology, Engineering and Mathematics (STEM) > Life, Health and Chemical Sciences
Faculty of Science, Technology, Engineering and Mathematics (STEM)
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Item ID: 53198
SWORD Depositor: Jisc Publications-Router
Depositing User: Jisc Publications-Router
Date Deposited: 22 Feb 2018 10:01
Last Modified: 22 May 2019 06:01
URI: http://oro.open.ac.uk/id/eprint/53198
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