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Altered neurotrophin receptor function in the developing prefrontal cortex leads to adult-onset dopaminergic hyperresponsivity and impaired prepulse inhibition of acoustic startle.

Abstract：

BACKGROUND:Survival and differentiation of neurons and the formation and maintenance of synapses in the cerebral cortex may be affected in schizophrenia. Since neurotrophins play an important role in these events, behavioral effects relevant to schizophrenia were investigated in rats that had compromised neurotrophin function during prefrontal cortical development. METHODS:Neonatal rat pups were injected into the developing prefrontal cortex with a depot preparation of p75 receptor antibody conjugated to saporin. Animals were tested for dopaminergic hyperresponsivity and prepulse inhibition of acoustic startle at 5 or 10 weeks. Neonatal and adult brain sections were examined for morphologic abnormality. RESULTS:Animals that received neonatal injections of p75 antibody conjugated to saporin showed significantly increased amphetamine-induced locomotion and rearing and impairment of prepulse inhibition of acoustic startle at 10 weeks of age but not at 5 weeks. Examination of adult brain sections revealed apparently normal structure, whereas neonatal brain sections showed apoptotic cells in the developing prefrontal cortex in pups that received p75 antibody conjugated to saporin. CONCLUSIONS:Compromised p75 neurotrophin receptor function in the developing prefrontal cortex may be associated with the manifestation of adult-onset dopaminergic hyperresponsivity and impaired prepulse inhibition and therefore may be involved in the pathogenesis of schizophrenia.

journal_name

Biol Psychiatry

journal_title

Biological psychiatry

authors

Rajakumar N,Leung LS,Ma J,Rajakumar B,Rushlow W

doi

10.1016/j.biopsych.2003.12.015

subject

Has Abstract

pub_date

2004-04-15 00:00:00

pages

797-803

issue

8

eissn

0006-3223

issn

1873-2402

pii

S0006322304000551

journal_volume

55

pub_type

杂志文章

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