Dihexa · research summary

Cognitive benefits of angiotensin IV and angiotensin-(1-7): A systematic review of experimental studies.

Neuroscience and biobehavioral reviews · 2018. Summary drawn from the study's full text. Each statement is followed by the exact sentence it comes from. This is a research summary, not medical advice.

Study type

Systematic review of experimental non-human studies
“Design:Systematic review of experimental (non-human) studies assessing cognitive effects of RAS peptides angiotensin-(3–8) [Ang IV] and angiotensin-(1–7) [Ang-(1–7)] and their receptors, the Ang IV receptor (AT4R) and the Mas receptor.”

Subjects

Rats and mice in experimental models of normal cognition or induced cognitive impairment
“Of the 32 included publications, 27 studied rats, and 5 studied mice.”

Sample size

32 studies included from 450 identified articles
“Of 450 articles identified, 32 met inclusion criteria.”

Duration

Literature search conducted up to July 2017; study durations varied from acute phases to 30 days
“All studies assessed cognition during days 1–3 following treatment, and 17 studies (53%) measured longer-term cognition during days 7–30.”

Reported findings

Ang IV and its analogs improved performance on spatial working memory and passive avoidance tasks in models of cognitive deficit
“In models of cognitive deficit, eight of nine studies found Ang IV and its analogs (Nle1-Ang IV, dihexa, LVV-hemorphin-7) improved performance on spatial working memory and passive avoidance tasks.”
Ang-(1–7) showed beneficial effects on memory in two of three studies
“Two of three studies examining Ang-(1–7) found it benefited memory.”
Removal of the Mas receptor was associated with reduced fear memory
“Mas receptor removal was associated with reduced fear memory in one study.”

Limitations stated by the authors

Heterogeneity in study designs prevented meta-analysis; low reporting of randomization and blinding
“Meta-analysis was not undertaken given the heterogeneity in study designs in terms of timing (pre-/post-training; pre-/post-testing) and route of administration [intracerebroventricular (i.c.v.), intrahippocampal (i.h.), subcutaneous (s.c.), intraperitoneal (i.p.), oral] of RAS peptides, species (mice vs. rats) and strain (e.g. Wistar vs. Sprague Dawley rats) differences, as well as amounts of the peptide administered and the cognitive tests used.”

Source: PubMed 29733881 · DOI 10.1016/j.neubiorev.2018.05.005 · all study summaries

Reported findings

Ang IV and its analogs improved performance on spatial working memory and passive avoidance tasks in models of cognitive deficit

“In models of cognitive deficit, eight of nine studies found Ang IV and its analogs (Nle1-Ang IV, dihexa, LVV-hemorphin-7) improved performance on spatial working memory and passive avoidance tasks.”

Ang-(1–7) showed beneficial effects on memory in two of three studies

“Two of three studies examining Ang-(1–7) found it benefited memory.”

Removal of the Mas receptor was associated with reduced fear memory

“Mas receptor removal was associated with reduced fear memory in one study.”

Limitations stated by the authors

Heterogeneity in study designs prevented meta-analysis; low reporting of randomization and blinding

“Meta-analysis was not undertaken given the heterogeneity in study designs in terms of timing (pre-/post-training; pre-/post-testing) and route of administration [intracerebroventricular (i.c.v.), intrahippocampal (i.h.), subcutaneous (s.c.), intraperitoneal (i.p.), oral] of RAS peptides, species (mice vs. rats) and strain (e.g. Wistar vs. Sprague Dawley rats) differences, as well as amounts of the peptide administered and the cognitive tests used.”