Exogenous l‐lactate promotes astrocyte plasticity but is not sufficient for enhancing striatal synaptogenesis or motor behavior in mice

Abstract

Over the last two decades, exercise has emerged as an effective tool to enhance neurogenesis and synaptogenesis in healthy animals (Cotman & Berchtold, 2002), as well as providing a non-pharmacological therapy for improving motor performance in individuals with Parkinson's disease (PD) (Petzinger et al., 2013). While the underlying molecular mechanisms responsible for the benefits of exercise are not yet fully elucidated, studies suggest a role for neurotrophic factors (NTFs) such as brain-derived neurotrophic factor (BDNF) in promoting

Knockdown of astrocytic monocarboxylate transporter 4 (MCT4) in the motor cortex leads to loss of dendritic spines and a deficit in motor learning

“…The ANLS is known to be coupled with synaptic activity, especially excitatory glutamatergic neurotransmission (Pellerin & Magistretti, 1994). Previous work by our lab and others have shown L-lactate may influence BDNF expression, and BDNF is known to be a key modulator of glutamatergic receptor expression and synaptic activity (El Hayek et al, 2019;Lundquist et al, 2021;Müller et al, 2020). Taken together, our findings support the potential role of MCT4 in regulating neuronal activity in M1 primary motor cortex and associated motor regions.…”

“…Monocarboxylate transporters, MCT1 through 4, have been shown to play a key role in cellular signaling and neuroenergetics through the transport of small molecules involved in metabolism and cell signaling including L-lactate, beta-hydroxybutyrate, and other ketones important for promoting neuroplasticity (Magistretti & Allaman, 2018). MCT4 is an astrocyte-specific monocarboxylate transporter, a constituent of the astrocyte-neuron lactate shuttle (ANLS), that plays a crucial role in regulating changes in neuronal activity and metabolism through the transport of L-lactate (Barros, 2013;Bélanger et al, 2011;Lundquist et al, 2021;Margineanu et al, 2018;Yang et al, 2014). In the last decade, MCT4 as part of the ANLS has also been implicated in neuroplasticity and learning.…”

Perception is associated with the brain’s metabolic response to sensory stimulation

“…Elevated brain lactate and glutamate levels are associated with wakefulness and memory formation, which naturally require the processing of incoming sensory stimuli, like the control exerted by the central visual pathways for either gating or filtering out behaviorally relevant or irrelevant visual information. As such, the metabolic responses to perceived, but not unperceived, sensory stimulation could be enabling factors for learning and memory, as indicated by the relevance of aerobic glycolysis and lactate in synaptic plasticity mechanisms ( Bueschke et al, 2021 ; Descalzi et al, 2019 ; DiNuzzo, 2016 ; Harris et al, 2019 ; Herrera-López et al, 2020 ; Jourdain et al, 2018 ; Kobayashi et al, 2019 ; Lundquist et al, 2021 ; Margineanu et al, 2018 ; Scavuzzo et al, 2020 ; Wang et al, 2019 ; Yang et al, 2014 ). In particular, aerobic glycolysis and lactate might reflect cortical information processing and, in turn, intracortical communication, in agreement with the relation between regional metabolic rates of glucose utilization and resting-state network dynamics in the cerebral cortex ( Jamadar et al, 2020 ; Noack et al, 2017 ; Spetsieris et al, 2015 ; Su et al, 2018 ; Thompson, 2018 ).…”

A mind in motion: Exercise improves cognitive flexibility, impulsivity and alters dopamine receptor gene expression in a Parkinsonian rat model

“…PB30.11–10, PCR Biosystems, Wayne, PA, USA) following manufacturer's guidelines before being diluted 1:5 in DNAse/RNAse free water and stored at −20 °C. Gene expression changes were measured with quantitative RT-PCR (qRT-PCR) as previously described ( Lundquist et al, 2019 , 2021 ). Briefly, qRT-PCR was run with 2 μl of cDNA and qPCRBIO SyGreen master mix (Cat.…”