Distinct roles of ascorbic acid in extracellular vesicles and free form: Implications for metabolism and oxidative stress in presymptomatic Huntington's disease.

Huntington's disease (HD) is a neurodegenerative disorder caused by a CAG trinucleotide repeat expansion in the first exon of the huntingtin gene. The huntingtin protein (Htt) is ubiquitously expressed and localized in several organelles, including endosomes, where it plays an essential role in intracellular trafficking. Presymptomatic HD is associated with a failure in energy metabolism and oxidative stress.

Altered lactate metabolism in Huntington's disease is dependent on GLUT3 expression.

Aims: Huntington's disease (HD) is a neurodegenerative disorder characterized by progressive abnormalities in cognitive function, mental state, and motor control. HD is characterized by a failure in brain energy metabolism. It has been proposed that monocarboxylates, such as lactate, support brain activity.

A simple solution for antibody signal enhancement in immunofluorescence and triple immunogold assays.

Immunolocalization techniques are standard in biomedical research. Tissue fixation with aldehydes and cell membrane permeabilization with detergents can distort the specific binding of antibodies to their high affinity epitopes. In immunofluorescence protocols, it is desirable to quench the sample's autofluorescence without reduction of the antibody-dependent signal.

Old Things New View: Ascorbic Acid Protects the Brain in Neurodegenerative Disorders.

Ascorbic acid is a key antioxidant of the Central Nervous System (CNS). Under brain activity, ascorbic acid is released from glial reservoirs to the synaptic cleft, where it is taken up by neurons. In neurons, ascorbic acid scavenges reactive oxygen species (ROS) generated during synaptic activity and neuronal metabolism where it is then oxidized to dehydroascorbic acid and released into the extracellular space, where it can be recycled by astrocytes.

Beyond the redox imbalance: Oxidative stress contributes to an impaired GLUT3 modulation in Huntington's disease.

Failure in energy metabolism and oxidative damage are associated with Huntington's disease (HD). Ascorbic acid released during synaptic activity inhibits use of neuronal glucose, favouring lactate uptake to sustain brain activity. Here, we observe a decreased expression of GLUT3 in STHdhQ111 cells (HD cells) and R6/2 mice (HD mice).

A failure in energy metabolism and antioxidant uptake precede symptoms of Huntington's disease in mice.

Huntington's disease has been associated with a failure in energy metabolism and oxidative damage. Ascorbic acid is a powerful antioxidant highly concentrated in the brain where it acts as a messenger, modulating neuronal metabolism. Using an electrophysiological approach in R6/2 HD slices, we observe an abnormal ascorbic acid flux from astrocytes to neurons, which is responsible for alterations in neuronal metabolic substrate preferences.

Ascorbic acid-dependent GLUT3 inhibition is a critical step for switching neuronal metabolism.

Intracellular ascorbic acid is able to modulate neuronal glucose utilization between resting and activity periods. We have previously demonstrated that intracellular ascorbic acid inhibits deoxyglucose transport in primary cultures of cortical and hippocampal neurons and in HEK293 cells. The same effect was not seen in astrocytes.

A metabolic switch in brain: glucose and lactate metabolism modulation by ascorbic acid.

In this review, we discuss a novel function of ascorbic acid in brain energetics. It has been proposed that during glutamatergic synaptic activity neurons preferably consume lactate released from glia. The key to this energetic coupling is the metabolic activation that occurs in astrocytes by glutamate and an increase in extracellular [K(+)].