| RRC ID |
88439
|
| 著者 |
Guercio GD, Anjos-Travassos Y, Rangel I, Costa S, Poleto A, Costa D, Chaiben R, de Villers-Sidani E, Panizzutti R.
|
| タイトル |
Auditory cognitive training improves prepulse inhibition in serine racemase mutant mice.
|
| ジャーナル |
Psychopharmacology (Berl)
|
| Abstract |
Evidence indicates that neuroplasticity-based cognitive training can improve cognition in patients with schizophrenia, but the individual response to training varies greatly between subjects. Hence, there is a need to understand the neurological underpinnings of cognitive training to reveal predictors of treatment response. D-serine is a crucial modulator of neuroplasticity, and decreased levels of D-serine may contribute to deficits in neuroplasticity in schizophrenia. Interestingly, we observed that training mice to identify auditory oddballs increased extracellular levels of D-serine in the hippocampus during training. Serine racemase (Srr) is the only source of brain D-serine; thus, it is possible that Srr may mediate the response to training. To test this hypothesis, we trained mice that have a mutated version of Srr (SrrY269*/SrrY269*) and reduced levels of D-serine in the same auditory training. SrrY269*/SrrY269* mice showed decreased performance during auditory training (defined as the capacity to discriminate an oddball during a sequence of tones). Importantly, auditory training improved prepulse inhibition (PPI) in SrrY269*/SrrY269* but not in wild-type mice. Finally, D-serine (100 mg/kg i.p.) given 30 min before training sessions to SrrY269*/SrrY269* mice improved training performance, but it did not enhance PPI. Taken together, our results show that D-serine is involved in the response to neuroplasticity-based auditory training and that PPI deficits can be improved by auditory oddball training even in the presence of neuroplasticity deficits.
|
| 巻・号 |
237(8)
|
| ページ |
2499-2508
|
| 公開日 |
2020-8-1
|
| DOI |
10.1007/s00213-020-05549-1
|
| PII |
10.1007/s00213-020-05549-1
|
| PMID |
32483676
|
| MeSH |
Acoustic Stimulation / methods*
Animals
Cognition / drug effects
Cognition / physiology*
Hippocampus / drug effects
Hippocampus / metabolism
Male
Mice
Mice, Transgenic
Neuronal Plasticity / drug effects
Neuronal Plasticity / physiology
Prepulse Inhibition / drug effects
Prepulse Inhibition / physiology*
Racemases and Epimerases / genetics*
Racemases and Epimerases / metabolism*
Schizophrenia / genetics
Schizophrenia / metabolism
Serine / pharmacology
Serine Racemase
|
| IF |
3.13
|
| リソース情報 |
| 実験動物マウス |
RBRC-GD000099 |
