PMID- 23010935
OWN - NLM
STAT- MEDLINE
DCOM- 20131216
LR  - 20211021
IS  - 1573-7365 (Electronic)
IS  - 0885-7490 (Linking)
VI  - 28
IP  - 2
DP  - 2013 Jun
TI  - Chronic hyperammonemia, glutamatergic neurotransmission and neurological 
      alterations.
PG  - 151-4
LID - 10.1007/s11011-012-9337-3 [doi]
AB  - This mini-review focus on our studies on alterations in glutamatergic 
      neurotransmission and their role in neurological alterations in rat models of 
      chronic hyperammonemia and hepatic encephalopathy (HE). Hyperammonemia impairs 
      the glutamate-nitric oxide (NO)-cGMP pathway in cerebellum, which is responsible 
      for reduced learning ability. We studied the underlying mechanisms and designed 
      treatments to restore the pathway and learning. This was achieved by treatment 
      with: phosphodiesterase 5 inhibitors, cGMP, anti-inflammatories (ibuprofen), p38 
      inhibitors or GABAA receptor antagonists (bicuculline). Hyperammonemia alters 
      signal transduction associated to metabotropic glutamate receptors (mGluRs). 
      Hypokinesia in hyperammonemia and HE is due to increased extracellular glutamate 
      and mGluR1 activation in substantia nigra; blocking this receptor restores motor 
      activity. The motor responses to mGluRs activation in nucleus accumbens (NAcc) 
      are altered in hyperammonemia and HE, with reduced dopamine and increased 
      glutamate release. This leads to activation of different neuronal circuits and 
      enhanced motor responses. These studies show that altered responses to activation 
      of NMDA receptors and mGluRs play essential roles in cognitive and motor 
      alterations in hyperammonemia and HE and provide new treatments restoring 
      cognitive and motor function.
FAU - Llansola, Marta
AU  - Llansola M
AD  - Laboratory of Neurobiology, Centro de Investigacion Principe Felipe, Eduardo 
      Primo Yufera, 3. 46012 Valencia, Spain.
FAU - Montoliu, Carmina
AU  - Montoliu C
FAU - Cauli, Omar
AU  - Cauli O
FAU - Hernandez-Rabaza, Vicente
AU  - Hernandez-Rabaza V
FAU - Agusti, Ana
AU  - Agusti A
FAU - Cabrera-Pastor, Andrea
AU  - Cabrera-Pastor A
FAU - Gimenez-Garzo, Carla
AU  - Gimenez-Garzo C
FAU - Gonzalez-Usano, Alba
AU  - Gonzalez-Usano A
FAU - Felipo, Vicente
AU  - Felipo V
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
DEP - 20120926
PL  - United States
TA  - Metab Brain Dis
JT  - Metabolic brain disease
JID - 8610370
RN  - 3KX376GY7L (Glutamic Acid)
SB  - IM
MH  - Animals
MH  - Chronic Disease
MH  - Cognition Disorders/etiology
MH  - Glutamic Acid/*physiology
MH  - Humans
MH  - Hyperammonemia/complications/*physiopathology
MH  - Nervous System Diseases/etiology/*physiopathology
MH  - Synaptic Transmission/*physiology
EDAT- 2012/09/27 06:00
MHDA- 2013/12/18 06:00
CRDT- 2012/09/27 06:00
PHST- 2012/08/13 00:00 [received]
PHST- 2012/09/19 00:00 [accepted]
PHST- 2012/09/27 06:00 [entrez]
PHST- 2012/09/27 06:00 [pubmed]
PHST- 2013/12/18 06:00 [medline]
AID - 10.1007/s11011-012-9337-3 [doi]
PST - ppublish
SO  - Metab Brain Dis. 2013 Jun;28(2):151-4. doi: 10.1007/s11011-012-9337-3. Epub 2012 
      Sep 26.