title: Matrix metalloproteinase (MMP) 9 transcription in mouse brain induced by fear learning.
abstract: Memory formation requires learning-based molecular and structural changes in neurons, whereas matrix metalloproteinase (MMP) 9 is involved in the synaptic plasticity by cleaving extracellular matrix proteins and, thus, is associated with learning processes in the mammalian brain. Because the mechanisms of MMP-9 transcription in the brain are poorly understood, this study aimed to elucidate regulation of MMP-9 gene expression in the mouse brain after fear learning. We show here that contextual fear conditioning markedly increases MMP-9 transcription, followed by enhanced enzymatic levels in the three major brain structures implicated in fear learning, i.e. the amygdala, hippocampus, and prefrontal cortex. To reveal the role of AP-1 transcription factor in MMP-9 gene expression, we have used reporter gene constructs with specifically mutated AP-1 gene promoter sites. The constructs were introduced into the medial prefrontal cortex of neonatal mouse pups by electroporation, and the regulation of MMP-9 transcription was studied after contextual fear conditioning in the adult animals. Specifically, -42/-50- and -478/-486-bp AP-1 binding motifs of the mouse MMP-9 promoter sequence have been found to play a major role in MMP-9 gene activation. Furthermore, increases in MMP-9 gene promoter binding by the AP-1 transcription factor proteins c-Fos and c-Jun have been demonstrated in all three brain structures under investigation. Hence, our results suggest that AP-1 acts as a positive regulator of MMP-9 transcription in the brain following fear learning.
authors.affiliation: From the Laboratory of Neurobiology and. Electronic address: k.ganguly@nencki.gov.pl.
authors.forename: Krishnendu
authors.initials: K
authors.lastname: Ganguly
authors.affiliation: From the Laboratory of Neurobiology and.
authors.forename: Emilia
authors.initials: E
authors.lastname: Rejmak
authors.affiliation: Laboratory of Neurobiology of Emotions, Nencki Institute, Pasteur 3, 02-093 Warsaw, Poland.
authors.forename: Marta
authors.initials: M
authors.lastname: Mikosz
authors.affiliation: From the Laboratory of Neurobiology and.
authors.forename: Evgeni
authors.initials: E
authors.lastname: Nikolaev
authors.affiliation: Laboratory of Neurobiology of Emotions, Nencki Institute, Pasteur 3, 02-093 Warsaw, Poland.
authors.forename: Ewelina
authors.initials: E
authors.lastname: Knapska
authors.affiliation: From the Laboratory of Neurobiology and. Electronic address: l.kaczmarek@nencki.gov.pl.
authors.forename: Leszek
authors.initials: L
authors.lastname: Kaczmarek
mesh_terms: D000818:Animals; D020029:Base Pairing / Q000235:genetics; D001483:Base Sequence; D001921:Brain / Q000201:enzymology* / Q000502:physiology*; D003213:Conditioning, Psychological; D049030:Dystroglycans / Q000378:metabolism; D005239:Fear; D015971:Gene Expression Regulation, Enzymologic; D007858:Learning; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D059372:Nucleotide Motifs / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding / Q000235:genetics; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D018808:Transcription Factor AP-1 / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D012333:RNA, Messenger; D018808:Transcription Factor AP-1; D049030:Dystroglycans; D020780:Matrix Metalloproteinase 9; C501830:Mmp9 protein, mouse
keywords: AP1 Transcription Factor; Amygdala; Electroporation; Fear Learning; Fos; Gene Regulation; Hippocampus; Jun Transcription Factor; Matrix Metalloproteinase 9; Medial Prefrontal Cortex