Facilitation of hippocampal synaptogenesis and spatial memory by C-terminal truncated Nle1-angiotensin IV analogs

Caroline C Benoist; John W Wright; Mingyan Zhu; Suzanne M Appleyard; Gary A Wayman; Joseph W Harding

doi:10.1124/jpet.111.182220

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Facilitation of hippocampal synaptogenesis and spatial memory by C-terminal truncated Nle1-angiotensin IV analogs

Journal article

Open access

Peer reviewed

Facilitation of hippocampal synaptogenesis and spatial memory by C-terminal truncated Nle1-angiotensin IV analogs

Caroline C Benoist, John W Wright, Mingyan Zhu, Suzanne M Appleyard, Gary A Wayman and Joseph W Harding

The Journal of pharmacology and experimental therapeutics, Vol.339(1), pp.35-44

10/2011

DOI: https://doi.org/10.1124/jpet.111.182220

Handle:

https://hdl.handle.net/2376/106538

PMCID: PMC3186286

PMID: 21719467

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Abstract

Immunohistochemistry

Memory - drug effects

Cell Count

Male

Peptide Fragments - pharmacology

Dendrites - ultrastructure

Structure-Activity Relationship

Hippocampus - drug effects

Dose-Response Relationship, Drug

Scopolamine Hydrobromide - pharmacology

Transfection

Dendritic Spines - drug effects

Muscarinic Antagonists - pharmacology

Receptors, Angiotensin - chemistry

Behavior, Animal - drug effects

Hippocampus - growth & development

Dendrites - drug effects

Synapses - drug effects

Cells, Cultured

Rats

Cognition - drug effects

Maze Learning - drug effects

Rats, Sprague-Dawley

Patch-Clamp Techniques

Animals

Scopolamine Hydrobromide - antagonists & inhibitors

Dendritic Spines - ultrastructure

Angiotensin IV (AngIV; Val(1)-Tyr(2)-Ile(3)-His(4)-Pro(5)-Phe(6))-related peptides have emerged as potential antidementia agents. However, their development as practical therapeutic agents has been impeded by a combination of metabolic instability, poor blood-brain barrier permeability, and an incomplete understanding of their mechanism of action. This study establishes the core structure contained within norleucine(1)-angiotensin IV (Nle(1)-AngIV) that is required for its procognitive activity. Results indicated that Nle(1)-AngIV-derived peptides as small as tetra- and tripeptides are capable of reversing scopolamine-induced deficits in Morris water maze performance. This identification of the active core structure contained within Nle(1)-AngIV represents an initial step in the development of AngIV-based procognitive drugs. The second objective of the study was to clarify the general mechanism of action of these peptides by assessing their ability to affect changes in dendritic spines. A correlation was observed between a peptide's procognitive activity and its capacity to increase spine numbers and enlarge spine head size. These data suggest that the procognitive activity of these molecules is attributable to their ability to augment synaptic connectivity.

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Title: Facilitation of hippocampal synaptogenesis and spatial memory by C-terminal truncated Nle1-angiotensin IV analogs
Creators: Caroline C Benoist - Department of Veterinary and Comparative, Washington State University, Pullman, Washington 99164-6520, USA
John W Wright
Mingyan Zhu
Suzanne M Appleyard
Gary A Wayman
Joseph W Harding
Publication Details: The Journal of pharmacology and experimental therapeutics, Vol.339(1), pp.35-44
Academic Unit: Psychology, Department of; Integrative Physiology and Neuroscience, Department of
Publisher: United States
Grant note: MH086032 / NIMH NIH HHS R01 MH086032 / NIMH NIH HHS
Identifiers: 99900546953501842
Language: English
Resource Type: Journal article