Astroglial nuclear factor-kappaB regulates learning and memory and synaptic plasticity in female mice.
Astrocytes play a pivotal role in regulating synaptic plasticity and synapse formation. The nuclear factor-kappa B (NF-kappaB) family of transcription factors has recently been demonstrated to be an important modulator of synaptic plasticity and learning/memory. In this study, we investigated the role of astroglial NF-kappaB in synaptic plasticity and learning/memory using transgenic mice over-expressing an N-terminal truncated form of inhibitor of NF-kappaB alpha (IkappaBalpha) in astrocytes (GFAP-IkappaBetaalpha-dn). We demonstrated that female transgenic mice, but not males, have robust deficits in hippocampal and extra-hippocampal-dependent learning and memory. We also determined that there are significant deficits in LTP and expression of metabotropic glutamate receptor 5 and post-synaptic density protein 95 (PSD95) in female transgenic mice. These findings indicate that astroglial NF-kappaB is an important regulator of learning/memory and synaptic plasticity.
Bracchi-Ricard
Valerie
V
The Miami Project to Cure Paralysis, Department of Neurological Surgery, University of Miami School of Medicine, Miami, Florida 33136, USA. vbracchi@miamiproject.med.miami.edu
Brambilla
Roberta
R
Levenson
Jonathan
J
Hu
Wen-Hui
WH
Bramwell
Annmarie
A
Sweatt
J David
JD
Green
Edward J
EJ
Bethea
John R
JR
D000704:Analysis of Variance; D000818:Animals; D001362:Avoidance Learning / Q000502:physiology; D001522:Behavior, Animal / Q000502:physiology*; D004558:Electric Stimulation; D005106:Exploratory Behavior / Q000502:physiology; D005260:Female; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology; D020672:I-kappa B Proteins / Q000235:genetics / Q000502:physiology*; D066298:In Vitro Techniques; D017774:Long-Term Potentiation / Q000235:genetics / Q000502:physiology*; D008297:Male; D018782:Maze Learning / Q000502:physiology*; D008568:Memory / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009474:Neurons / Q000502:physiology; D011930:Reaction Time; D012737:Sex Factors; D009435:Synaptic Transmission / Q000502:physiology* / Q000528:radiation effects; D013997:Time Factors
C083487:I kappa B beta protein; D020672:I-kappa B Proteins; D049452:Green Fluorescent Proteins