Elsevier

Neuroscience Letters

Volume 115, Issue 1, 17 July 1990, Pages 97-102
Neuroscience Letters

Intraventricular infusions of antibodies to amyloid-β-protein precursor impair the acquisition of a passive avoidance response in the rat

https://doi.org/10.1016/0304-3940(90)90524-DGet rights and content

Abstract

Intraventricular infusions of an antiserum raised against a 14 amino acid residue in the extracellular domain of amyloid-β-protein precursor significantly decreased stepdown latency, at both 24 h and 48 h recall times, in rats trained to avoid an electroshock by remaining on a platform. The antiserum was effective when infused up to 2.5 h following training and no retention deficit was noted when it was administered at 4h or 6h after training. An antiserum generated against a 17 amino acid residue of the A4 amyloid peptide had no effect on learning. Thus the amyloid precursor protein, which is aberrantly processed in Alzheimer's disease, appears to be directly involved in memory formation.

References (30)

  • D. Goldgaber et al.

    Characterisation and chromosomal localisation of a cDNA encoding brain amyloid of Alzheimer's disease

    Science

    (1987)
  • D.C. Gowda et al.

    Relation of the amyloid β protein precursor to heparan sulphate proteoglycans

    Science

    (1989)
  • W.T. Greenough et al.

    Synaptic structural correlates of information storage in mammalian nervous system

  • J. Kang et al.

    The precursor of Alzheimer's disease amyloid A4 protein resembles a cell surface receptor

    Nature (Lond.)

    (1987)
  • R.E. Kelly et al.

    Membrane traffic in neurons and peptide-secreting cells

  • Cited by (90)

    • Role of Environment, Epigenetics, and Synapses in Cognitive Enhancement

      2015, Cognitive Enhancement: Pharmacologic, Environmental and Genetic Factors
    • Amyloid β precursor protein as a molecular target for amyloid β-induced neuronal degeneration in Alzheimer's disease

      2013, Neurobiology of Aging
      Citation Excerpt :

      For example, application of sAPP to cultured primary neurons promoted long-term survival, enhanced neurite outgrowth, increased synaptic formation, and protected cultured neurons against various toxic stimuli (Mattson, 1997). Extending these observations, intracranial infusion of sAPP-specific antibodies impaired memory, whereas application of sAPP has a memory-enhancing effect (Doyle et al., 1990; Meziane et al., 1998). Together, these findings indicated that sAPP modulates cellular activities involved in cognitive processes, including the functionality and maintenance of synapses and neurites.

    • Behavioral and neurochemical characterization of mice deficient in the N-type Ca <sup>2+</sup> channel α <inf>1B</inf> subunit

      2010, Behavioural Brain Research
      Citation Excerpt :

      These tests are based on the natural tendency of rodents to alternate in their choices of arms visited when they are placed in a multi-arm maze. Importantly, spontaneous alternation behavior is dependent on intact hippocampal function, supported by the cognitive deficits observed in hippocampal-lesioned rodents [12], making it a relevant task for studying the role of the α1B subunit of N-type calcium channels. In the current study, CaV2.2−/− mice exhibited no significant deficits in spontaneous alternation behavior in the Y-maze.

    • Endogenous secreted amyloid precursor protein-α regulates hippocampal NMDA receptor function, long-term potentiation and spatial memory

      2008, Neurobiology of Disease
      Citation Excerpt :

      Given the discrepancies arising from exogenous sAPPα administration, and the potential relevance of decreased protein levels to AD pathogenesis and cognitive decline, it is important to understand the neural effects of reducing the activity of endogenous sAPPα. Studies using sAPP-targeted antibodies in rats and chicks have shown deficits in passive- and active-avoidance memory tasks (Doyle et al., 1990; Huber et al., 1993; Mileusnic et al., 2000), but the antibodies used did not distinguish the functions of sAPPα from related proteins such as sAPPβ (a less potent neurotrophic fragment generated by β- and γ-secretase processing). Here, we have used two strategies to target and inhibit endogenous sAPPα function in the hippocampus, and we have determined the effects of restoring sAPPα with exogenous recombinant protein.

    View all citing articles on Scopus
    View full text