AngIV-Analog Dihexa Rescues Cognitive Impairment and Recovers Memory in the APP/PS1 Mouse via the PI3K/AKT Signaling Pathway.

Preclinical animal study investigating the effects of Dihexa on cognitive function and neuroinflammation in APP/PS1 mice.

“In our study, we used different doses of Dihexa, which can be orally administered and cross the BBB in APP/PS1 mice.”

Male APP/PS1 transgenic mice and age-matched wild-type (C57) mice.

“Male (APP/PS1) mice and wild-type (C57) mice were purchased from Beijing Zhishan Company (Beijing, China).”

Groups consisted of 6 to 12 mice per group depending on the specific experiment.

“Columns represent mean ± SD (n = 12 per group).”

The treatment period lasted for three months, with mice aged from six to nine months during the study.

“The Dihexa was administered intraperitoneally to the APP/PS1 mice from six to nine months old.”

Dihexa administration increased brain AngIV levels and improved spatial learning and memory in APP/PS1 mice.

“Dihexa restored spatial learning and cognitive functions in the Morris water maze test.”

Dihexa increased neuronal cell counts and synaptophysin protein expression while decreasing astrocyte and microglia activation.

“Dihexa increased the neuronal cells and the expression of SYP protein in APP/PS1 mice in Nissl staining.”

Dihexa activated the PI3K/AKT signaling pathway, and this effect was reversed by the PI3K inhibitor wortmannin.

“Dihexa activated the PI3K/AKT signaling pathway, while PI3K inhibitor wortmannin significantly reversed the anti-inflammatory and anti-apoptotic effects of APP/PS1 mice.”