Neuronal and astroglial monocarboxylate transporters play key but distinct roles in hippocampus-dependent learning and memory formation

Netzahualcoyotzi, Citlalli; Pellerin, Luc

doi:10.1016/j.pneurobio.2020.101888

Cited by 52 publications

(43 citation statements)

References 75 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In the last decade, MCT4 as part of the ANLS has also been implicated in neuroplasticity and learning. For example, in the hippocampus, knockdown of MCT4 has been shown to impair both long-term memory and synaptic integrity (Netzahualcoyotzi & Pellerin, 2020;Suzuki et al, 2011). However, the role of astrocyte-specific MCT4 in facilitating neuroplasticity and motor learning of the M1 primary motor cortex, remains a gap in knowledge.…”

Section: Discussionmentioning

confidence: 99%

“…The majority of studies reporting the role of the ANLS and L-lactate transport involvement in neuroplasticity, including memory and learning, have focused on the hippocampus (Alberini et al, 2018). For example, genetic knockdown of the ANLS has been repeatedly shown to impair long-term potentiation and dendritic spine density as well as spatial memory acquisition and consolidation in the rodent brain (Harris et al, 2019;Netzahualcoyotzi & Pellerin, 2020;Suzuki et al, 2011;Vezzoli et al, 2020). A more recent study has also shown that the ANLS plays a role in the prefrontal cortex, with knockdown of MCT4 resulting in a loss of a stress-induced coping response (Yin et al, 2021).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

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

Lundquist

Llewellyn

Kishi

et al. 2021

Preprint

View full text Add to dashboard Cite

Monocarboxylate transporters (MCTs) shuttle molecules, including L-lactate, involved in metabolism and cell signaling of the central nervous system. Astrocyte-specific MCT4 is a key component of the astrocyte-neuron lactate shuttle (ANLS) and is important for neuroplasticity and learning of the hippocampus. However, the importance of astrocyte-specific MCT4 in neuroplasticity of the M1 primary motor cortex remains unknown. In this study, we investigated astrocyte-specific MCT4 in motor learning and neuroplasticity of the M1 primary motor cortex using a cell-type specific shRNA knockdown of MCT4. Knockdown of astrocyte-specific MCT4 resulted in impaired motor performance and learning on the accelerating rotarod. In addition, MCT4 knockdown was associated with a reduction of neuronal dendritic spine density and spine width and decreased protein expression of PSD95 and Arc. Using near-infrared-conjugated 2-deoxyglucose uptake as a surrogate marker for neuronal activity, MCT4 knockdown was also associated with decreased neuronal activity in the M1 primary motor cortex and associated motor regions including the dorsal striatum and ventral thalamus. Our study supports a potential role for astrocyte-specific MCT4 and the ANLS in the neuroplasticity of the M1 primary motor cortex. Targeting MCT4 may serve to enhance neuroplasticity and motor repair in several neurological disorders, including Parkinson's disease and stroke.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

Lundquist

Llewellyn

Kishi

et al. 2021

Preprint

View full text Add to dashboard Cite

show abstract

“…Indeed, training in an inhibitory avoidance task is accompanied by a rapid and sustained increase in extracellular lactate in the hippocampus (179), whereas inhibiting glycogen phosphorylase, the rate limiting enzyme in glycogenolysis, using 1,4-dideoxy-1,4,-imino-D-arabinitol 15 min prior to training abolishes the lactate rise, impairs LTP, and results in memory deficits (179,180). In addition, inhibiting astrocytic lactate export by reducing MCT1 or MCT4 expression, or blocking neuronal lactate uptake by reducing MCT2 expression both result in memory impairments (179)(180)(181). The former can be rescued by lactate and its energetic equivalent pyruvate, but not by glucose (179,180).…”

Section: The Astrocyte-neuron Lactate Shuttlementioning

confidence: 99%

Reactive Astrocytes: Critical Players in the Development of Chronic Pain

2021

View full text Add to dashboard Cite

Chronic pain is associated with long term plasticity of nociceptive pathways in the central nervous system. Astrocytes can profoundly affect synaptic function and increasing evidence has highlighted how altered astrocyte activity may contribute to the pathogenesis of chronic pain. In response to injury, astrocytes undergo a shift in form and function known as reactive astrogliosis, which affects their release of cytokines and gliotransmitters. These neuromodulatory substances have been implicated in driving the persistent changes in central nociceptive activity. Astrocytes also release lactate which neurons can use to produce energy during synaptic plasticity. Furthermore, recent research has provided insight into lactate's emerging role as a signaling molecule in the central nervous system, which may be involved in directly modulating neuronal and astrocytic activity. In this review, we present evidence for the involvement of astrocyte-derived tumor necrosis factor alpha in pain-associated plasticity, in addition to research suggesting the potential involvement of gliotransmitters D-serine and adenosine-5′-triphosphate. We also discuss work implicating astrocyte-neuron metabolic coupling, and the possible role of lactate, which has been sparsely studied in the context of chronic pain, in supporting pathological changes in central nociceptive activity.

show abstract

“…Adult neurogenesis is one of the plasticity mechanisms in the brain that has been strongly associated with memory formation [ 70 , 71 , 72 ]. Defects in the neurogenic process have been related to some human neurological and psychiatric diseases [ 73 , 74 ], as well as to cognitive alterations in animal models [ 75 , 76 , 77 ].…”

Section: Cannabinoid Effect On Neurogenesismentioning

confidence: 99%

Early Consumption of Cannabinoids: From Adult Neurogenesis to Behavior

Netzahualcoyotzi

Rodríguez-Serrano

Chávez-Hernández

et al. 2021

IJMS

Self Cite

View full text Add to dashboard Cite

The endocannabinoid system (ECS) is a crucial modulatory system in which interest has been increasing, particularly regarding the regulation of behavior and neuroplasticity. The adolescent–young adulthood phase of development comprises a critical period in the maturation of the nervous system and the ECS. Neurogenesis occurs in discrete regions of the adult brain, and this process is linked to the modulation of some behaviors. Since marijuana (cannabis) is the most consumed illegal drug globally and the highest consumption rate is observed during adolescence, it is of particular importance to understand the effects of ECS modulation in these early stages of adulthood. Thus, in this article, we sought to summarize recent evidence demonstrating the role of the ECS and exogenous cannabinoid consumption in the adolescent–young adulthood period; elucidate the effects of exogenous cannabinoid consumption on adult neurogenesis; and describe some essential and adaptive behaviors, such as stress, anxiety, learning, and memory. The data summarized in this work highlight the relevance of maintaining balance in the endocannabinoid modulatory system in the early and adult stages of life. Any ECS disturbance may induce significant modifications in the genesis of new neurons and may consequently modify behavioral outcomes.

show abstract

Neuronal and astroglial monocarboxylate transporters play key but distinct roles in hippocampus-dependent learning and memory formation

Cited by 52 publications

References 75 publications

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

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

Reactive Astrocytes: Critical Players in the Development of Chronic Pain

Early Consumption of Cannabinoids: From Adult Neurogenesis to Behavior

Contact Info

Product

Resources

About