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\begin{document}

\title{Maternal treatment of cyclic glycine-proline improves memory, astrocyte
plasticity, vascularization and GluR-1 expression of adult offspring in
rats}



\author[1]{Gagan Singh-Mallah}%
\author[2]{Maryam Ardalan}%
\author[1]{Da Kang}%
\author[3]{Kuljeet Singh}%
\author[3]{Chris Mcmahon}%
\author[2]{Carina Mallard}%
\author[1]{Jian Guan}%
\affil[1]{The University of Auckland Faculty of Medical and Health Sciences}%
\affil[2]{University of Gothenburg Sahlgrenska Academy}%
\affil[3]{AgResearch Ltd Ruakura Research Centre}%


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  \date{May 25, 2024}


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\begin{abstract}
Abstract Background and Purpose: Cyclic glycine-proline (cGP) regulates
the function of insulin-like growth factor-1 (IGF-1), which is essential
for post-natal brain development and adult cognitive function. We
evaluated the efficacy of maternally administered cGP on spatial memory
and the association with astrocytic plasticity, vascularization and
synaptic expressions in the hippocampus of their adult offspring.
Experimental Approach: Either cGP or saline was orally administered to
Sprague Dawley dams from post-natal days 8-22. Spatial memory was
evaluated using Morris Water Maze tests between post-natal days 70-75.
Using immunohistochemistry and stereological analysis, we evaluated
capillary density, astrocytic processes and expression of synaptophysin
and glutamate receptor-1 (GluR-1) in the CA1 stratum-radiatum of the
hippocampus. Key Results: Compared to the saline-treated offspring,
cGP-treated offspring showed higher path efficiency of entry to the
platform zone (p=0.03) and lower average heading errors to the platform
zone (p=0.02). Astrocyte processes of cGP-treated offspring were longer
and larger with more branches (p=0.03-0.0001) than saline-treated
offspring. The density of capillaries (p=0.007) and GluR-1 (p=0.02) were
also higher in cGP-treated offspring. The average heading error was
negatively correlated with the length (r=-0.69), volume (r=-0.72) and
number of astrocytic branches (r=-0.65). Independent of treatment, the
changes of astrocyte processes were positively correlated with the
density of capillaries (r=0.73-0.78) and expression of GluR-1
(r=0.66-0.68). Conclusion and Implications: The improved spatial memory
of cGP-treated offspring after post-natal maternal administration may be
mediated via promoting astrocytic plasticity, vascularization and
glutamate trafficking. Therefore, cGP may have a role in regulating
IGF-1 function during brain development.%
\end{abstract}%



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