Systemic administration of a nerve growth factor conjugate reverses age- related cognitive dysfunction and prevents cholinergic neuron atrophy

Cristina Bäckman, Gregory M. Rose, Barry J. Hoffer, Michael A. Henry, Raymond T. Bartus, Phillip Friden, Ann Charlotte Granholm

Research output: Contribution to journalArticle

121 Citations (Scopus)

Abstract

Intraventricular administration of nerve growth factor (NGF) in rats has been shown to reduce age-related atrophy of central cholinergic neurons and the accompanying memory impairment. Intraventricular administration of NGF is necessary because NGF will not cross the blood-brain barrier (BBB). Here we have used a novel carrier system, consisting of NGF covalently linked to an anti-transferrin receptor antibody (OX-26), to transport biologically active NGF across the BBB. In our experiment, aged (24 months old) Fischer 344 rats received intravenous injections of the OX-26-NGF conjugate or a control solution (a mixture of unconjugated OX-26 and NGF) twice weekly for 6 weeks. The OX-26-NGF injections resulted in a significant improvement in spatial learning in previously impaired rats but disrupted the learning ability of previously unimpaired rats. Neuroanatomical analyses showed that OX-26-NGF conjugate treatment resulted in a significant increase in cholinergic cell size in the medial septal region of rats initially impaired in spatial learning. These results indicate the potential use of the transferrin receptor antibody delivery system for treatment of CNS disorders with neurotrophic proteins.

Original languageEnglish (US)
Pages (from-to)5437-5442
Number of pages6
JournalJournal of Neuroscience
Volume16
Issue number17
StatePublished - Sep 1 1996
Externally publishedYes

Fingerprint

Cholinergic Neurons
Nerve Growth Factor
Atrophy
Transferrin Receptors
Blood-Brain Barrier
Septum of Brain
Cognitive Dysfunction
Aptitude
Antibodies
Active Biological Transport
Inbred F344 Rats
Nerve Growth Factors
Cell Size
Intravenous Injections
Cholinergic Agents
Learning
Injections

Keywords

  • acetylcholine
  • Alzheimer's disease
  • basal forebrain
  • nerve growth factor
  • neurotrophic factors
  • plasticity
  • regeneration
  • septal nucleus

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Bäckman, C., Rose, G. M., Hoffer, B. J., Henry, M. A., Bartus, R. T., Friden, P., & Granholm, A. C. (1996). Systemic administration of a nerve growth factor conjugate reverses age- related cognitive dysfunction and prevents cholinergic neuron atrophy. Journal of Neuroscience, 16(17), 5437-5442.

Systemic administration of a nerve growth factor conjugate reverses age- related cognitive dysfunction and prevents cholinergic neuron atrophy. / Bäckman, Cristina; Rose, Gregory M.; Hoffer, Barry J.; Henry, Michael A.; Bartus, Raymond T.; Friden, Phillip; Granholm, Ann Charlotte.

In: Journal of Neuroscience, Vol. 16, No. 17, 01.09.1996, p. 5437-5442.

Research output: Contribution to journalArticle

Bäckman, C, Rose, GM, Hoffer, BJ, Henry, MA, Bartus, RT, Friden, P & Granholm, AC 1996, 'Systemic administration of a nerve growth factor conjugate reverses age- related cognitive dysfunction and prevents cholinergic neuron atrophy', Journal of Neuroscience, vol. 16, no. 17, pp. 5437-5442.
Bäckman, Cristina ; Rose, Gregory M. ; Hoffer, Barry J. ; Henry, Michael A. ; Bartus, Raymond T. ; Friden, Phillip ; Granholm, Ann Charlotte. / Systemic administration of a nerve growth factor conjugate reverses age- related cognitive dysfunction and prevents cholinergic neuron atrophy. In: Journal of Neuroscience. 1996 ; Vol. 16, No. 17. pp. 5437-5442.
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