PMID- 24874304
OWN - NLM
STAT- MEDLINE
DCOM- 20151022
LR  - 20211021
IS  - 1573-4978 (Electronic)
IS  - 0301-4851 (Linking)
VI  - 41
IP  - 8
DP  - 2014 Aug
TI  - MMP-9 gene ablation mitigates hyperhomocystenemia-induced cognition and hearing 
      dysfunction.
PG  - 4889-98
LID - 10.1007/s11033-014-3425-x [doi]
AB  - Hyperhomocysteinemia (HHcy) is associated with cognitive decline and hearing loss 
      due to vascular dysfunction. Although we have shown that HHcy-induced increased 
      expression of matrix metalloproteinase-9 (MMP-9) is associated with cochlear 
      pathology in cystathionine-beta-synthase heterozygous (CBS(+/-)) mice, it is still 
      unclear whether MMP-9 contributes to functional deficit in cognition and hearing. 
      Therefore, we hypothesize that HHcy-induced MMP-9 activation causes vascular, 
      cerebral and cochlear remodeling resulting in diminished cognition and hearing. 
      Wildtype (WT), CBS(+/-), MMP-9(-/-) and CBS(+/-)/MMP-9(-/-) double knock-out 
      (DKO) mice were genotyped and used. Doppler flowmetry of internal carotid artery 
      (ICA) was performed for peak systolic velocity [PSV], pulsatility index [PI] and 
      resistive index [RI]. Cognitive functions were assessed by Novel Object 
      Recognition Test (NORT) and for cochlear function Auditory brainstem response 
      (ABR) was elicited. Peak systolic velocity, pulsatility and resistive indices of 
      ICA were decreased in CBS(+/-) mice, indicating reduced perfusion. ABR threshold 
      was increased and maximum ABR amplitude and NORT indices (recognition, 
      discrimination) were decreased in CBS(+/-) mice compared to WT and MMP-9(-/-). 
      All these parameters were attenuated in DKO mice suggesting a significant role of 
      MMP-9 in HHcy-induced vascular, neural and cochlear pathophysiology. Regression 
      analysis of PSV with ABR and cognitive parameters revealed significant 
      correlation (0.44-0.58). For the first time, MMP-9 has been correlated directly 
      to functional deficits of brain and cochlea, and found to have a significant 
      role. Our data suggests a dual pathology of HHcy occurring due to a decrease in 
      blood supply (vasculo-neural and vasculo-cochlear) and direct tissue remodeling.
FAU - Bhargava, Seema
AU  - Bhargava S
AD  - Department of Biochemistry, Sir Ganga Ram Hospital, Rajinder Nagar, New Delhi, 
      110060, India, bhargavaseema6@gmail.com.
FAU - Pushpakumar, Sathnur
AU  - Pushpakumar S
FAU - Metreveli, Naira
AU  - Metreveli N
FAU - Givvimani, Srikanth
AU  - Givvimani S
FAU - Tyagi, Suresh C
AU  - Tyagi SC
LA  - eng
PT  - Journal Article
PL  - Netherlands
TA  - Mol Biol Rep
JT  - Molecular biology reports
JID - 0403234
RN  - EC 3.4.24.35 (Matrix Metalloproteinase 9)
SB  - IM
MH  - Animals
MH  - Blood Flow Velocity
MH  - Carotid Artery, Internal/physiology
MH  - Cognition Disorders/*etiology
MH  - *Gene Deletion
MH  - Genotype
MH  - Hearing Disorders/*etiology
MH  - Hyperhomocysteinemia/*complications
MH  - Laser-Doppler Flowmetry
MH  - Matrix Metalloproteinase 9/*genetics
MH  - Mice
MH  - Mice, Knockout
MH  - Pulsatile Flow
MH  - Regression Analysis
EDAT- 2014/05/31 06:00
MHDA- 2015/10/23 06:00
CRDT- 2014/05/31 06:00
PHST- 2014/05/31 06:00 [entrez]
PHST- 2014/05/31 06:00 [pubmed]
PHST- 2015/10/23 06:00 [medline]
AID - 10.1007/s11033-014-3425-x [doi]
PST - ppublish
SO  - Mol Biol Rep. 2014 Aug;41(8):4889-98. doi: 10.1007/s11033-014-3425-x.