期刊
MOLECULAR NEUROBIOLOGY
卷 59, 期 5, 页码 2874-2893出版社
SPRINGER
DOI: 10.1007/s12035-022-02772-z
关键词
c-Jun N-terminal kinase (JNK); Extracellular matrix; TAOK2; Brain-derived neurotrophic factor (BDNF); Bicuculline; Synaptic plasticity; Glycoprotein biosynthesis
资金
- University of Glasgow, College of Medical Veterinary and Life Sciences Doctoral Training Programme
The study finds that enzymatic digestion of PNNs by ChABC produces an immature molecular phenotype, which is distinct from mature plasticity. Furthermore, the study highlights the involvement of TAOK signaling in BDNF regulation of plasticity and PNNs.
Perineuronal nets (PNNs) are specialised extracellular matrix structures which preferentially enwrap fast-spiking (FS) parvalbumin interneurons and have diverse roles in the cortex. PNN maturation coincides with closure of the critical period of cortical plasticity. We have previously demonstrated that BDNF accelerates interneuron development in a c-Jun-NH2-terminal kinase (JNK)-dependent manner, which may involve upstream thousand-and-one amino acid kinase 2 (TAOK2). Chondroitinase-ABC (ChABC) enzymatic digestion of PNNs reportedly reactivates 'juvenile-like' plasticity in the adult CNS. However, the mechanisms involved are unclear. We show that ChABC produces an immature molecular phenotype in cultured cortical neurons, corresponding to the phenotype prior to critical period closure. ChABC produced different patterns of PNN-related, GABAergic and immediate early (IE) gene expression than well-characterised modulators of mature plasticity and network activity (GABA(A)-R antagonist, bicuculline, and sodium-channel blocker, tetrodotoxin (TTX)). ChABC downregulated JNK activity, while this was upregulated by bicuculline. Bicuculline, but not ChABC, upregulated Bdnf expression and ERK activity. Furthermore, we found that BDNF upregulation of semaphorin-3A and IE genes was TAOK mediated. Our data suggest that ChABC heightens structural flexibility and network disinhibition, potentially contributing to 'juvenile-like' plasticity. The molecular phenotype appears to be distinct from heightened mature synaptic plasticity and could relate to JNK signalling. Finally, we highlight that BDNF regulation of plasticity and PNNs involves TAOK signalling.
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