Cited by 37Schizophrenia research and treatmentNeurotransmitter Receptor Influence on BehaviorNeuroscience and Neuropharmacology Research

Impairment of cognitive performance after reelin knockdown in the medial prefrontal cortex of pubertal or adult rats

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Brosda, Jan, Dietz, Frank, Koch, Michael·2011·Neurobiology of Disease

Abstract

The glycoprotein reelin is important for embryonic neuronal migration. During adulthood reelin possibly acts as a modulator of synaptic plasticity. Several studies link reduced levels of reelin messenger RNA and protein to the pathophysiology of certain neuropsychiatric disorders. However, little is known about reelin's role for behavioral and cognitive functions in vivo. Therefore, the effect of a reelin knockdown in the medial prefrontal cortex (mPFC) of Wistar rats was examined in behavioral tasks related to neuropsychiatric disorders, such as schizophrenia. Rats treated with reelin antisense phosphothioate oligonucleotides in the mPFC during puberty or adulthood were tested for prepulse inhibition (PPI) of the acoustic startle reflex, spatial working memory, object recognition, and locomotor activity. Reelin quantification in the mPFC was assessed by Western blotting. Local reelin knockdown during puberty or adulthood induced (1) a PPI deficit as well as (2) an impairment of spatial working memory and object recognition following pubertal injections. Western blot analyses showed a distinct and highly selective reelin knockdown in the rats' mPFC. These results indicate that mPFC reelin signaling plays an important role in behavioral tasks with relevance to e.g. schizophrenia. Understanding reelin's function as a neurotrophic modulator of the extracellular matrix may help to achieve new insights into the etiology of certain neuropsychiatric diseases and foster prospective treatment strategies.

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Crossref · 10.1016/j.nbd.2011.07.008

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  • The time and place at which Reelin signaling is reduced may prove to be the deciding factor for the extent of cognitive impact that defective Reelin signaling may have.

    “The time and place at which Reelin signaling is reduced may prove to be the deciding factor for the extent of cognitive impact that defective Reelin signaling may have (97).”

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Authors
Brosda, J., Dietz, F., & Koch, M.
Affiliations
University of Bremen (DE)
Venue
Neurobiology of Disease
Publisher
Elsevier BV
Published
2011-11
Volume
44
Issue
2
Pages
239-247
ISSN
0969-9961 (ISSN-L)
OpenAlex
W2041055359
Cited by
37
References
95
Citations by year
2024: 1 · 2023: 1 · 2022: 1 · 2021: 1 · 2020: 3 · 2019: 3 · 2018: 3 · 2017: 3 · 2016: 8 · 2015: 1 · 2014: 3 · 2013: 3 · 2012: 6
FWCI
2.62
Type
journal article
Language
en
Open access
Locations
  • Neurobiology of Disease (publishedVersion)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
Deutsche Forschungsgemeinschaft
Topics
  • Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Keywords
reelin, medial prefrontal cortex, antisense oligonucleotides, prepulse inhibition, acoustic startle response, spatial working memory, object recognition, puberty, schizophrenia, neuropsychiatric disorders, synaptic plasticity, neurotrophic factors, extracellular matrix
MeSH terms
Reelin Protein, Age Factors, Animals, Cognition Disorders, Disease Models, Animal, Male, Nerve Tissue Proteins, Serine Endopeptidases, Sexual Maturation, Cell Adhesion Molecules, Neuronal, Extracellular Matrix Proteins, Rats, Wistar, Prefrontal Cortex, Mood Disorders, Oligoribonucleotides, Antisense, Rats, Gene Knockdown Techniques

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