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Review
. 2023 May 12:16:1181397.
doi: 10.3389/fnmol.2023.1181397. eCollection 2023.

Building better brains: the pleiotropic function of neurotrophic factors in postnatal cerebellar development

Pia Boxy  1   2   3 , Anders Nykjær  1   2   3 , Lilian Kisiswa  1   2   3
Affiliations
Review

Building better brains: the pleiotropic function of neurotrophic factors in postnatal cerebellar development

Pia Boxy et al. Front Mol Neurosci. .

Abstract

The cerebellum is a multifunctional brain region that controls diverse motor and non-motor behaviors. As a result, impairments in the cerebellar architecture and circuitry lead to a vast array of neuropsychiatric and neurodevelopmental disorders. Neurotrophins and neurotrophic growth factors play essential roles in the development as well as maintenance of the central and peripheral nervous system which is crucial for normal brain function. Their timely expression throughout embryonic and postnatal stages is important for promoting growth and survival of both neurons and glial cells. During postnatal development, the cerebellum undergoes changes in its cellular organization, which is regulated by a variety of molecular factors, including neurotrophic factors. Studies have shown that these factors and their receptors promote proper formation of the cerebellar cytoarchitecture as well as maintenance of the cerebellar circuits. In this review, we will summarize what is known on the neurotrophic factors' role in cerebellar postnatal development and how their dysregulation assists in developing various neurological disorders. Understanding the expression patterns and signaling mechanisms of these factors and their receptors is crucial for elucidating their function within the cerebellum and for developing therapeutic strategies for cerebellar-related disorders.

Keywords: cerebellum; development; developmental disorder; neurotrophic factors; signaling/signaling pathways.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Neurotrophic factors regulate postnatal cerebellar development. This schematic diagram depicts the families of neurotrophic factors that regulate survival, differentiation, and migration of cerebellar neurons as well as neurite circuit formation and maintenance. BDNF, brain-derived neurotrophic factor; CNTF, ciliary neurotrophic factor; EGF, epidermal growth factor; GDNF, glial-derived neurotrophic factor; NGF, nerve growth factor; NT-3, neurotrophin-3; NT-4, neurotrophin-4; PGRN, progranulin; TGF-b, transforming growth factor beta. Figure produced in BioRender.
Figure 2
Figure 2
Different processes during postnatal cerebellar development require neurotrophic action. This schematic illustration depicts several stages of postnatal cerebellar development that involve the neurotrophic factors. EGL, external granule layer; oEGL, outer EGL; iEGL, inner EGL; PCL; Purkinje cell layer; ML, molecular layer; (I)GL, (internal) granule layer; WM, white matter; DCN, deep cerebellar nuclei; PC, Purkinje cell; CGN; cerebellar granule cell; MLI, molecular layer interneuron; BG, Bergmann glia; BDNF, brain-derived neurotrophic factor; CNTF, ciliary neurotrophic factor; EGF, epidermal growth factor; GDNF, glial-derived neurotrophic factor; NGF, nerve growth factor; NT-3, neurotrophin-3; NT-4, neurotrophin-4; PGRN, progranulin; TGF-b, transforming growth factor beta. Figure produced in BioRender.
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References

    1. Abe H., Okazawa M., Nakanishi S. (2012). Gene regulation via excitation and Bdnf is mediated by induction and phosphorylation of the Etv1 transcription factor in cerebellar granule cells. Proc. Natl. Acad. Sci. 109, 8734–8739. doi: 10.1073/pnas.1206418109, PMID: - DOI - PMC - PubMed
    1. Abe K., Saito H. (1992). Protective effect of epidermal growth factor on glutamate neurotoxicity in cultured cerebellar neurons. Neurosci. Res. 14, 117–123. doi: 10.1016/0168-0102(92)90087-S, PMID: - DOI - PubMed
    1. Abe K., Takayanagi M., Saito H. (1991). Basic fibroblast growth factor and epidermal growth factor promote survival of primary cultured cerebellar neurons from neonatal rats. Jpn. J. Pharmacol. 56, 113–116. doi: 10.1016/S0021-5198(19)39906-8, PMID: - DOI - PubMed
    1. Abe K., Takayanagi M., Saito H. (1992). Neurotrophic effects of epidermal growth factor on cultured brain neurons are blocked by protein kinase inhibitors. Japan. J. Pharmacol. 59, 259–261. doi: 10.1254/jjp.59.259, PMID: - DOI - PubMed
    1. Adamaszek M., D’agata F., Ferrucci R., Habas C., Keulen S., Kirkby K. C., et al. . (2017). Consensus paper: cerebellum and emotion. Cerebellum 16, 552–576. doi: 10.1007/s12311-016-0815-8, PMID: - DOI - PubMed