L-Lactate Promotes Adult Hippocampal Neurogenesis.

Yaeli Lev-Vachnish,Alexander Varvak,Aviva Rotter-Maskowitz,Raneen Nicola,Tomer Illouz,Sharon Cadury,Asael Roichman,Eitan Okun,Noa Feldman,Ravit Madar

doi:10.3389/fnins.2019.00403

Yaeli Lev-Vachnish, Alexander Varvak + Show 8 more

Open Access

https://doi.org/10.3389/fnins.2019.00403

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Abstract

Neurogenesis, the formation of new neurons in the adult brain, is important for memory formation and extinction. One of the most studied external interventions that affect the rate of adult neurogenesis is physical exercise. Physical exercise promotes adult neurogenesis via several factors including brain-derived neurotrophic factor (BDNF) and vascular endothelial growth factor (VEGF). Here, we identified L-lactate, a physical exercise-induced metabolite, as a factor that promotes adult hippocampal neurogenesis. While prolonged exposure to L-lactate promoted neurogenesis, no beneficial effect was exerted on cognitive learning and memory. Systemic pharmacological blocking of monocarboxylate transporter 2 (MCT2), which transports L-lactate to the brain, prevented lactate-induced neurogenesis, while 3,5-dihydroxybenzoic acid (3,5-DHBA), an agonist for the lactate-receptor hydroxycarboxylic acid receptor 1 (HCAR1), did not affect adult neurogenesis. These data suggest that L-lactate partially mediates the effect of physical exercise on adult neurogenesis, but not cognition, in a MCT2-dependent manner.

Highlights

Adult hippocampal neurogenesis, the process of forming new neurons in the adult brain, has sparked great interest following the observation that hippocampal granule cells are generated in adult rodents, a process which decreases significantly as the mice age (Kempermann, 2015)
In order to mimic mild-to-intensive physical exercise-induced lactate levels in the blood, mice were injected with 1.75 g/kg L-lactate, or phosphate buffered saline (PBS) (n = 3) and lactate were measured in blood samples taken at multiple time points afterward
Since the discovery by van Praag et al (1999b) that voluntary physical exercise enhances hippocampal adult neurogenesis, many efforts have been made to dissect the mechanisms behind this phenomenon

Summary

Introduction

The process of forming new neurons in the adult brain, has sparked great interest following the observation that hippocampal granule cells are generated in adult rodents, a process which decreases significantly as the mice age (Kempermann, 2015). Multiple studies in rodents have shown that adult neurogenesis can modulate specific aspects of learning and memory (Sahay et al, 2011; Goncalves et al, 2016). Adult hippocampal neurogenesis is essential for certain memory processes. Adult neurogenesis has been linked to cognitive flexibility, the ability to avoid interference between novel and previously formed memories, as was demonstrated in reversal learning of different tasks such as a Morris water maze (Epp et al, 2016), an active place avoiding task (Burghardt et al, 2012) and in a touch-screen discriminating task (Swan et al, 2014)

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