Journal
PHARMACOLOGICAL RESEARCH
Volume 173, Issue -, Pages -Publisher
ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1016/j.phrs.2021.105832
Keywords
Reelin; Schizophrenia; Recognition memory; Behavioral test; MK-801
Categories
Funding
- AMED [JP20dm0107087, 21wm0425007h0001]
- Japan Society for the Promotion of Science (JSPS) KAKENHI [JP17H04031, 20H03428, 20K07082]
- Uehara Memorial Foundation
- SRF, Toyoaki Scholarship Foundation
- Grants-in-Aid for Scientific Research [20H03428, 20K07082] Funding Source: KAKEN
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The study showed that microinjection of recombinant Reelin into the medial prefrontal cortex prevented recognition memory impairment induced by MK-801, highlighting the potential therapeutic effects of Reelin on cognitive deficits associated with schizophrenia. Despite this positive effect, Reelin treatment did not ameliorate deficits in sensory-motor gating and short-term memory in the animal model of schizophrenia. The results suggest that Reelin acts on its receptors to suppress neural activity in the mPFC, thereby preventing cognitive deficits induced by MK-801.
Reelin, a large extracellular matrix protein, helps to regulate neuronal plasticity and cognitive function. Several studies have shown that Reelin dysfunction, resulting from factors such as mutations in gene RELN or low Reelin expression, is associated with schizophrenia (SCZ). We previously reported that microinjection of Reelin into cerebral ventricle prevents phencyclidine-induced cognitive and sensory-motor gating deficits. However, it remains unclear whether and how Reelin ameliorates behavioral abnormalities in the animal model of SCZ. In the present study, we evaluated the effect of recombinant Reelin microinjection into the medial prefrontal cortex (mPFC) on abnormal behaviors induced by MK-801, an N-methyl-D-aspartate receptor antagonist. Microinjection of Reelin into the mPFC prevented impairment of recognition memory of MK-801-treated mice in the novel object recognition test (NORT). On the other hand, the same treatment had no effect on deficits in sensory-motor gating and short-term memory in the pre-pulse inhibition and Y-maze tests, respectively. To establish the neural substrates that respond to Reelin, the number of c-Fos-positive cells in the mPFC was determined. A significant increase in c-Fos-positive cells in the mPFC of MK-801-treated mice was observed when compared with salinetreated mice, and this change was suppressed by microinjection of Reelin into the mPFC. A K2360/2467A Reelin that cannot bind to its receptor failed to ameliorate MK-801-induced cognitive deficits in NORT. These results suggest that Reelin prevents MK-801-induced recognition memory impairment by acting on its receptors to suppress neural activity in the mPFC of mice.
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