LRP1 in Adult-Born Neural Stem Cells Modulates Neurogenesis and Hippocampal Memory

TL;DR

LRP1 in adult neural stem cells affects brain cell growth and memory, suggesting it could be a target for treating memory-related disorders.

Contribution

LRP1 is identified as a novel regulator of hippocampal neurogenesis and memory function in adult-born neural stem cells.

Findings

LRP1 knockout in neural stem cells impairs hippocampal-dependent memory.

LRP1 loss reduces dendritic complexity in newborn neurons.

LRP1 knockout increases the number of adult-born hippocampal neurons over time.

Abstract

What are the main findings?
Using a mouse LRP1 knockout model, we show that LRP1 loss in neural stem cells leads to impairments in hippocampal-dependent memory.LRP1 knockout reduced dendritic complexity in newborn neurons and increased the total number of adult-born hippocampal neurons in 10-month-old mice.

Using a mouse LRP1 knockout model, we show that LRP1 loss in neural stem cells leads to impairments in hippocampal-dependent memory.

LRP1 knockout reduced dendritic complexity in newborn neurons and increased the total number of adult-born hippocampal neurons in 10-month-old mice.

What are the implication of the main findings?
It reveals the essential role of LRP1 in neural stem cell biology and hippocampal neurogenesis.It implicates a role for LRP1 in hippocampal dysfunction that could contribute to multiple disorders, emphasizing the potential for targeting LRP1 in therapeutic strategies.

It reveals the essential role of LRP1 in neural stem cell biology and hippocampal neurogenesis.

It implicates a role for LRP1 in hippocampal dysfunction that could contribute to multiple disorders, emphasizing the potential for targeting LRP1 in therapeutic strategies.

(1) Background: Adult neurogenesis within the hippocampus modulates hippocampal memory and is often dysregulated in diseases that cause memory dysfunction, notably Alzheimer’s disease. We have discovered a novel modulator of hippocampal neurogenesis—low-density lipoprotein receptor-related protein 1 (LRP1). (2) Methods: Using an inducible knockout of LRP1, male and female mice were subject to loss of LRP1, specifically in adult-born neural stem cells at 3 months of age. (3) Results: After 6 months with the knockout, animals without LRP1 in adult-born neural stem cells displayed behavioral phenotypes consistent with deficits in working memory and hippocampal-mediated spatial memory. We also found that over time, increasing numbers of adult-born LRP1-knockout neurons were present, although those neurons were morphologically less complex with fewer dendrites than controls. Our data suggest that the increase in the total number of adult-born neurons 6 months after knockout is due to a subtle increase in hippocampal proliferation over time. (4) Conclusions: Altogether, our data suggest that LRP1 is an important and previously unknown regulator of hippocampal neurogenesis.

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