Chronic minocycline treatment improves social recognition memory in adult male Fmr1 knockout mice.
Fragile X syndrome (FXS) is caused by a mutation in the Fmr1 gene that leads to silencing of the gene and a loss of its gene product, Fragile X mental retardation protein (FMRP). Some of the key behavioral phenotypes for FXS include abnormal social anxiety and sociability. Here we show that Fmr1 knock-out (KO) mice exhibit impaired social recognition when presented with a novel mouse, and they display normal social interactions in other sociability tests. Administering minocycline to Fmr1 KO mice throughout critical stages of neural development improved social recognition memory in the novel mouse recognition task. To determine if synaptic changes in the prefrontal cortex (PFC) could have played a role in this improvement, we examined PSD-95, a member of the membrane-associated guanylate kinase family, and signaling molecules (ERK1/2, and Akt) linked to synaptic plasticity in the PFC. Our analyses indicated that while minocycline treatment can enhance behavioral performance, it does not enhance expression of PSD-95, ERK1/2 or Akt in the PFC.
Division of Medical Sciences, University of Victoria, Victoria, British Columbia, Canada.
Suk Yu
SY
Yau
Division of Medical Sciences, University of Victoria, Victoria, British Columbia, Canada.
Christine
C
Chiu
Division of Medical Sciences, University of Victoria, Victoria, British Columbia, Canada.
Mariana
M
Vetrici
Division of Medical Sciences, University of Victoria, Victoria, British Columbia, Canada. Electronic address: brain64@uvic.ca.
Brian R
BR
Christie
D000818:Animals; D004195:Disease Models, Animal; D000076122:Disks Large Homolog 4 Protein / Q000378:metabolism; D051860:Fragile X Messenger Ribonucleoprotein 1 / Q000235:genetics / Q000502:physiology*; D005600:Fragile X Syndrome / Q000235:genetics / Q000503:physiopathology* / Q000517:prevention & control / Q000523:psychology*; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008911:Minocycline / Q000008:administration & dosage*; D009473:Neuronal Plasticity / Q000187:drug effects*; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D021641:Recognition, Psychology / Q000502:physiology*; D012919:Social Behavior; D013569:Synapses / Q000187:drug effects / Q000378:metabolism
D000076122:Disks Large Homolog 4 Protein; D051860:Fragile X Messenger Ribonucleoprotein 1; D008911:Minocycline; D051057:Proto-Oncogene Proteins c-akt; C501447:Dlg4 protein, mouse; C497684:Fmr1 protein, mouse
Fragile X syndrome; Minocycline; Prefrontal cortex; Signaling molecules; Social behaviors