PMID- 19591848
OWN - NLM
STAT- MEDLINE
DCOM- 20100304
LR  - 20220331
IS  - 1095-9319 (Electronic)
IS  - 0026-2862 (Print)
IS  - 0026-2862 (Linking)
VI  - 78
IP  - 3
DP  - 2009 Dec
TI  - Reproductive age-related changes in the blood brain barrier: expression of IgG 
      and tight junction proteins.
PG  - 413-24
LID - 10.1016/j.mvr.2009.06.009 [doi]
AB  - We previously demonstrated that there is a significantly greater transfer of 
      intravenously-injected Evan's blue dye into the forebrain of acyclic 
      (reproductive senescent) females compared to young adult females, indicating that 
      blood brain barrier permeability is compromised in the reproductive senescent 
      forebrain. The present study examined brain IgG expression and microvessel tight 
      junction proteins to assess ovarian age-related changes in microvascular 
      permeability, and further compared young and senescent females with age-matched 
      males to distinguish changes attributable to age and reproductive senescence. 
      Blood brain barrier breakdown are often associated with increased extravasation 
      of plasma proteins and high levels of immunoglobulin G (IgG) in brain. In the 
      present study, IgG expression was dramatically increased in the hippocampus and 
      thalamus, but not the hypothalamus of reproductive senescent females compared to 
      young adult females. In males, IgG expression was increased in all these regions 
      in middle-aged animals (aged-matched to senescent females) as compared to young 
      males (age-matched to the young adult females). Furthermore, the proportion of 
      hippocampal microvessels with perivascular IgG immunoreactivity was significantly 
      greater in reproductive senescent females as compared to young adult females, 
      while middle-aged males and young adult males did not differ. The tight junctions 
      between adjacent microvascular endothelial cells regulated by transmembrane 
      proteins such as claudin-5 and occludin play a critical role in maintaining the 
      blood brain barrier integrity. Increased hippocampal IgG expression in senescent 
      females was paralleled by poor junctional localization of the tight junction 
      protein claudin-5 in hippocampal microvessels. However, there was no difference 
      in hippocampal claudin-5 localization between young adult and middle-aged males, 
      indicating that dysregulation of this junctional protein was associated with 
      ovarian aging. Parallel studies in human brain microvessels also revealed 
      age-dependent disruption in claudin-5 distribution in post-menopausal women 
      compared to pre-menopausal women. Collectively, these data support the hypothesis 
      that constitutive loss of barrier integrity in the forebrain during reproductive 
      senescence may be due, in part, to the selective loss of tight junction proteins 
      in endothelial junctions.
FAU - Bake, Shameena
AU  - Bake S
AD  - Department of Neuroscience and Experimental Therapeutics, TAMHSC College of 
      Medicine, College Station, TX 77843, USA.
FAU - Friedman, Jonathan A
AU  - Friedman JA
FAU - Sohrabji, Farida
AU  - Sohrabji F
LA  - eng
GR  - R01 AG028303/AG/NIA NIH HHS/United States
GR  - R01 AG027684-03/AG/NIA NIH HHS/United States
GR  - R01 AG027684/AG/NIA NIH HHS/United States
GR  - AG027684/AG/NIA NIH HHS/United States
GR  - R01 AG028303-03/AG/NIA NIH HHS/United States
GR  - AG028303/AG/NIA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20090708
PL  - United States
TA  - Microvasc Res
JT  - Microvascular research
JID - 0165035
RN  - 0 (Claudins)
RN  - 0 (Immunoglobulin G)
RN  - 0 (Membrane Proteins)
RN  - 0 (OCLN protein, human)
RN  - 0 (Occludin)
RN  - 0 (Ocln protein, rat)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Aging/*metabolism
MH  - Animals
MH  - Blood-Brain Barrier/*metabolism
MH  - Claudins/*metabolism
MH  - Female
MH  - Hippocampus/blood supply
MH  - Humans
MH  - Immunoglobulin G/analysis/*metabolism
MH  - Male
MH  - Membrane Proteins/*metabolism
MH  - Microvessels/metabolism
MH  - Middle Aged
MH  - Occludin
MH  - Ovariectomy
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Thalamus/blood supply
MH  - Tight Junctions/*metabolism
PMC - PMC2784250
MID - NIHMS131603
EDAT- 2009/07/14 09:00
MHDA- 2010/03/05 06:00
PMCR- 2010/12/01
CRDT- 2009/07/14 09:00
PHST- 2009/02/17 00:00 [received]
PHST- 2009/06/08 00:00 [revised]
PHST- 2009/06/25 00:00 [accepted]
PHST- 2009/07/14 09:00 [entrez]
PHST- 2009/07/14 09:00 [pubmed]
PHST- 2010/03/05 06:00 [medline]
PHST- 2010/12/01 00:00 [pmc-release]
AID - S0026-2862(09)00181-2 [pii]
AID - 10.1016/j.mvr.2009.06.009 [doi]
PST - ppublish
SO  - Microvasc Res. 2009 Dec;78(3):413-24. doi: 10.1016/j.mvr.2009.06.009. Epub 2009 
      Jul 8.