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Administration of cyclic glycine-proline during infancy improves adult spatial memory, astrocyte plasticity,
Gagandeep Singh-Mallah1,2,3,4,5,6, Maryam Ardalan6, Dali Kang1
1Department of Pharmacology and Clinical Pharmacology, School of Medical Sciences, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand.
Insights
Cyclic glycine-proline (cGP), a breast milk nutrient, enhanced spatial memory in adult rats. Infancy cGP supplementation promoted brain development, potentially via insulin-like growth factor-1 (IGF-1) pathway regulation.
Area of Science:
- Neuroscience
- Developmental Biology
- Nutritional Science
Background:
- Cyclic glycine-proline (cGP) is a naturally occurring nutrient in breast milk.
- cGP influences insulin-like growth factor-1 (IGF-1) function, crucial for brain development and cognitive function.
- IGF-1 plays a vital role in post-natal brain maturation and adult cognitive processes.
Purpose of the Study:
- To investigate the long-term effects of infantile cyclic glycine-proline (cGP) administration on spatial memory in adult rats.
- To examine the impact of cGP on hippocampal histology, including capillaries, astrocytes, synaptophysin, and glutamate receptor-1.
- To explore the potential mechanisms by which cGP influences brain development and cognitive function.
Main Methods:
- Infant rats received oral cGP or saline from post-natal days 8-22 via lactating dams.
- Spatial memory was assessed in adulthood (post-natal days 70-75) using the Morris water maze.
- Hippocampal CA1 stratum radiatum was analyzed for changes in capillaries, astrocytes, synaptophysin, and glutamate receptor-1 expression.
Main Results:
- cGP-treated rats exhibited improved spatial memory, demonstrated by higher path efficiency and fewer heading errors towards the platform.
- Histological analysis revealed increased capillary density, enhanced astrocytic processes (longer and larger), and elevated glutamate receptor-1 expression in cGP-treated rats.
- A correlation was observed between reduced heading errors and increased capillaries, along with larger and longer astrocytic branches.
Conclusions:
- Infantile cGP supplementation leads to moderate, long-lasting improvements in adult spatial memory.
- The memory-enhancing effects of cGP may be mediated by promoting astrocytic plasticity, vascularization, and glutamate trafficking in the hippocampus.
- cGP holds potential as a modulator of IGF-1 function during critical brain development periods.
Abstract:
Cyclic glycine-proline (cGP) is a natural nutrient of breast milk and plays a role in regulating the function of insulin-like growth factor-1 (IGF-1). IGF-1 function is essential for post-natal brain development and adult cognitive function. We evaluated the effects of cGP on spatial memory and histological changes in the hippocampus of the adult rats following infancy administration. Infant rats were treated with either cGP or saline between post-natal days 8 and 22 via oral administration to lactating dams. The spatial memory was evaluated between post-natal days 70 and 75 using Morris water maze tests. The changes of capillaries, astrocytes, synaptophysin and glutamate receptor-1 were examined in the CA1 stratum radiatum of the hippocampus. Compared to saline-treated group, cGP-treated group showed higher path efficiency of entry and lower average heading errors to the platform zone. cGP-treated group also showed longer, larger and more astrocytic processes, more capillaries and higher glutamate receptor-1 expression. The rats made less average heading error to the platform zone have more capillaries, larger and longer astrocytic branches. Thus cGP treatment/supplementation during infancy moderately improved adulthood spatial memory. This long-lasting effect of cGP on memory could be mediated via promoting astrocytic plasticity, vascularization and glutamate trafficking. Therefore, cGP may have a role in regulating IGF-1 function during brain development.
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