Juvenile Treatment with a Novel mGluR2 Agonist/mGluR3 Antagonist Compound, LY395756, Reverses Learning Deficits and Cognitive Flexibility Impairments in Adults in A Neurodevelopmental Model of Schizophrenia

anon79999497 · February 19, 2017, 3:57pm

ncbi.nlm.nih.gov

Juvenile treatment with a novel mGluR2 agonist/mGluR3 antagonist compound, LY395756, reverses learning deficits and cognitive flexibility impairments in adults in a neurodevelopmental model of schizophrenia.

ML Li, Y Gulchina, SA Monaco, B Xing, BR Ferguson, YC Li, F Li, XQ Hu and WJ Gao, Neurobiology of learning and memory, Apr 2017

Schizophrenia (SCZ) is a neurodevelopmental psychiatric disorder, in which cognitive function becomes disrupted at early stages of the disease. Although the mechanisms underlying cognitive impairments remain unclear, N-methyl-D-aspartate receptors (NMDAR) hypofunctioning in the prefrontal cortex (PFC) has been implicated. Moreover, cognitive symptoms in SCZ are usually unresponsive to treatment with current antipsychotics and by onset, disruption of the dopamine system, not NMDAR hypofunctioning, dominates the symptoms. Therefore, treating cognitive deficits at an early stage is a realistic approach. In this study, we tested whether an early treatment targeting mGluR2 would be effective in ameliorating cognitive impairments in the methylazoxymethanol acetate (MAM) model of SCZ. We investigated the effects of an mGluR2 agonist/mGluR3 antagonist, LY395756 (LY39), on the NMDAR expression and function in juveniles, as well as cognitive deficits in adult rats after juvenile treatment. We found that gestational MAM exposure induced a significant decrease in total protein levels of the NMDAR subunit, NR2B, and a significant increase of pNR2BTyr1472 in the juvenile rat PFC. Treatment with LY39 in juvenile MAM-exposed rats effectively recovered the disrupted NMDAR expression. Furthermore, a subchronic LY39 treatment in juvenile MAM-exposed rats also alleviated the learning deficits and cognitive flexibility impairments when tested with a cross-maze based set-shifting task in adults. Therefore, our study demonstrates that targeting dysfunctional NMDARs with an mGluR2 agonist during the early stage of SCZ could be an effective strategy in preventing the development and progression in addition to ameliorating cognitive impairments of SCZ.

far_cry0 · February 19, 2017, 4:00pm

Lot about cognition. .we want something for negative symptoms …

Chess24 · February 19, 2017, 4:02pm

We want treatment for cognitive symptoms, and negative as well.
But for functioning I think that cognition is very very important.

far_cry0 · February 19, 2017, 4:03pm

I think negative’s paramount right…

Chess24 · February 19, 2017, 4:05pm

both are important. Some suffer more cognitively and some from negative symptoms.
They are often talked about together.
Some include cognition in negative symptoms.
How is your cognition far_cry?

far_cry0 · February 19, 2017, 4:07pm

My cognition is bad eraz…i cant study…

Chess24 · February 19, 2017, 4:10pm

cognition is also important for work… cognition is very important for functioning.

far_cry0 · February 19, 2017, 4:12pm

Yes eraz negatives make u dull and cognition will make u ass…

Anon10 · February 20, 2017, 12:21am

Sometimes cognitive symptoms can present as negative symptoms, for e.g. say you have a short attention span (cognitive sx) so you can’t get anything done. A doctor might clinically evaluate you as having avolition or amotivation (negative sx). One particularly interesting overlap which I suffer from personally is alogia (negative sx) vs verbal fluency deficit (cognitive sx). Which one is it? perhaps a combination of both. We may find that medicaments which treat cognitive symptoms wipe out negative sx along with cognitives in one fell swoop.

anon89143308 · February 20, 2017, 6:56am

i think they are related to each other so maybe they have the same cause.