PMID- 29080716
OWN - NLM
STAT- MEDLINE
DCOM- 20180710
LR  - 20191210
IS  - 1873-7544 (Electronic)
IS  - 0306-4522 (Linking)
VI  - 367
DP  - 2017 Dec 26
TI  - Postnatal Proteasome Inhibition Promotes Amyloid-beta Aggregation in Hippocampus and 
      Impairs Spatial Learning in Adult Mice.
PG  - 47-59
LID - S0306-4522(17)30749-2 [pii]
LID - 10.1016/j.neuroscience.2017.10.021 [doi]
AB  - Ubiquitin-proteasome system (UPS) has emerged as major molecular mechanism which 
      modulates synaptic plasticity. However, very little is known about what happens 
      if this system fails during postnatal brain development. In the present study, 
      MG132 was administered intracerebroventricularly in BALB/c mice pups at postnatal 
      day one (P1), a very crucial period for synaptogenesis. Both 20S proteasome and 
      calpain activities were found to be reduced in the mid brain of 
      MG132-administered pups after 24 h. Mice (P40) which received MG132 on P1 were 
      subjected to Morris water maze (MWM) training. Analysis showed spatial learning 
      and memory of MG132 mice was significantly impaired when compared to age-matched 
      controls. Hematoxylin and eosin as well as Cresyl Violet staining revealed 
      substantial loss of cellular connections, distorted architecture and increased 
      pyknosis in hippocampal CA1 and CA3 regions of MG132 mice. Immunohistochemical 
      analysis of MG132 mice showed increased accumulation of intracellular amyloid-beta 
      in hippocampal cells when compared to control. Moreover, double immunostaining 
      revealed increased expression of amyloid precursor protein C-terminal fragments 
      (APP-CTFbeta) without affecting beta-secretase expression in MG132 mice. Real-Time PCR 
      analyses showed significant increase in hippocampal expression of 
      alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor subunit 
      glutamate A1 (GluA1), but no change in the brain-derived neurotrophic factor 
      (Bdnf) expression in MG132 mice. Western blot analyses showed decreased levels of 
      pThr286-CaMKIIalpha:CaMKIIalpha and pSer133-CREB:CREB ratio but increased pro:mature BDNF 
      ratio in the hippocampus of MG132 mice. Taken together, postnatal proteasome 
      inhibition could lead to accumulation of intracellular amyloid-beta protein 
      aggregates, which mediate hippocampus-dependent spatial memory impairments in 
      adult mice.
CI  - Copyright (c) 2017 IBRO. Published by Elsevier Ltd. All rights reserved.
FAU - Sunkaria, Aditya
AU  - Sunkaria A
AD  - Department of Biotechnology, National Institute of Pharmaceutical Education and 
      Research - Ahmedabad, Gandhinagar, Gujarat, India; Department of Biochemistry, 
      Panjab University, Chandigarh, India. Electronic address: 
      adityasunkaria@gmail.com.
FAU - Yadav, Aarti
AU  - Yadav A
AD  - Department of Biochemistry, Panjab University, Chandigarh, India.
FAU - Bhardwaj, Supriya
AU  - Bhardwaj S
AD  - Department of Dermatology, Postgraduate Institute of Medical Education and 
      Research, Chandigarh, India.
FAU - Sandhir, Rajat
AU  - Sandhir R
AD  - Department of Biochemistry, Panjab University, Chandigarh, India.
LA  - eng
PT  - Journal Article
DEP - 20171026
PL  - United States
TA  - Neuroscience
JT  - Neuroscience
JID - 7605074
RN  - 0 (Amyloid beta-Peptides)
RN  - 0 (Amyloid beta-Protein Precursor)
RN  - 0 (Eukaryotic Initiation Factor-2)
RN  - 0 (Leupeptins)
RN  - 0 (Proteasome Inhibitors)
RN  - 0 (Receptors, AMPA)
RN  - EC 3.4.- (Amyloid Precursor Protein Secretases)
RN  - EC 3.4.23.- (Aspartic Acid Endopeptidases)
RN  - EC 3.4.23.46 (Bace1 protein, mouse)
RN  - EC 3.4.25.1 (Proteasome Endopeptidase Complex)
RN  - RF1P63GW3K (benzyloxycarbonylleucyl-leucyl-leucine aldehyde)
RN  - TFZ3H25BS1 (glutamate receptor ionotropic, AMPA 1)
SB  - IM
MH  - Amyloid Precursor Protein Secretases/metabolism
MH  - Amyloid beta-Peptides/*metabolism
MH  - Amyloid beta-Protein Precursor/metabolism
MH  - Animals
MH  - Animals, Newborn
MH  - Aspartic Acid Endopeptidases/metabolism
MH  - Disease Models, Animal
MH  - Eukaryotic Initiation Factor-2/genetics/metabolism
MH  - Female
MH  - Hippocampus/drug effects/growth & development/*metabolism
MH  - Learning Disabilities/chemically induced/*pathology
MH  - Leupeptins/toxicity
MH  - Male
MH  - Maze Learning/drug effects
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Proteasome Endopeptidase Complex/*metabolism
MH  - Proteasome Inhibitors/toxicity
MH  - Protein Aggregation, Pathological/chemically induced
MH  - Receptors, AMPA/genetics/metabolism
MH  - Spatial Learning/drug effects/*physiology
OTO - NOTNLM
OT  - APP-CTF
OT  - Bdnf
OT  - MG132
OT  - proteasome
OT  - spatial learning
EDAT- 2017/10/31 06:00
MHDA- 2018/07/11 06:00
CRDT- 2017/10/30 06:00
PHST- 2017/05/04 00:00 [received]
PHST- 2017/09/09 00:00 [revised]
PHST- 2017/10/16 00:00 [accepted]
PHST- 2017/10/31 06:00 [pubmed]
PHST- 2018/07/11 06:00 [medline]
PHST- 2017/10/30 06:00 [entrez]
AID - S0306-4522(17)30749-2 [pii]
AID - 10.1016/j.neuroscience.2017.10.021 [doi]
PST - ppublish
SO  - Neuroscience. 2017 Dec 26;367:47-59. doi: 10.1016/j.neuroscience.2017.10.021. 
      Epub 2017 Oct 26.