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Learning-Induced Gene Expression in the Hippocampus Reveals a Role of Neuron -Astrocyte Metabolic Coupling in Long Term Memory.

Tadi M, Allaman I, Lengacher S, Grenningloh G, Magistretti PJ - PLoS ONE (2015)

Bottom Line: The quantitative determination of mRNA levels revealed learning-induced changes in the expression of genes thought to be involved in astrocyte-neuron metabolic coupling in a time dependent manner.Twenty four hours following IA training, an enhanced gene expression was seen, particularly for genes encoding monocarboxylate transporters 1 and 4 (MCT1, MCT4), alpha2 subunit of the Na/K-ATPase and glucose transporter type 1.Together, these observations indicate that neuron-glia metabolic coupling undergoes metabolic adaptations following learning as indicated by the change in expression of key metabolic genes.

View Article: PubMed Central - PubMed

Affiliation: Brain Mind Institute, Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland.

ABSTRACT
We examined the expression of genes related to brain energy metabolism and particularly those encoding glia (astrocyte)-specific functions in the dorsal hippocampus subsequent to learning. Context-dependent avoidance behavior was tested in mice using the step-through Inhibitory Avoidance (IA) paradigm. Animals were sacrificed 3, 9, 24, or 72 hours after training or 3 hours after retention testing. The quantitative determination of mRNA levels revealed learning-induced changes in the expression of genes thought to be involved in astrocyte-neuron metabolic coupling in a time dependent manner. Twenty four hours following IA training, an enhanced gene expression was seen, particularly for genes encoding monocarboxylate transporters 1 and 4 (MCT1, MCT4), alpha2 subunit of the Na/K-ATPase and glucose transporter type 1. To assess the functional role for one of these genes in learning, we studied MCT1 deficient mice and found that they exhibit impaired memory in the inhibitory avoidance task. Together, these observations indicate that neuron-glia metabolic coupling undergoes metabolic adaptations following learning as indicated by the change in expression of key metabolic genes.

No MeSH data available.


Related in: MedlinePlus

Glycogen regulation following IA learning.The table summarizes the changes seen in the mRNA expression of genes related to glycogen metabolism following IA task at 3, 24 or 72 hours after training (A) or 3 hours after testing (B). An upright arrow indicates significant induction of the gene in dorsal hippocampus of the CS-US group (P < 0.05, versus CS group, n = 7-8/group) whereas an upright arrow in brackets indicates an almost significant induction (i.e. P values very close to significance [P<0.05]) and a “-“entry indicates no significant difference across the two groups. Data were statistically analyzed using two-tailed Student’s t test. For abbreviations, see materials and methods section.
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pone.0141568.g005: Glycogen regulation following IA learning.The table summarizes the changes seen in the mRNA expression of genes related to glycogen metabolism following IA task at 3, 24 or 72 hours after training (A) or 3 hours after testing (B). An upright arrow indicates significant induction of the gene in dorsal hippocampus of the CS-US group (P < 0.05, versus CS group, n = 7-8/group) whereas an upright arrow in brackets indicates an almost significant induction (i.e. P values very close to significance [P<0.05]) and a “-“entry indicates no significant difference across the two groups. Data were statistically analyzed using two-tailed Student’s t test. For abbreviations, see materials and methods section.

Mentions: Recently, we have shown that astrocytic glycogen metabolism in the hippocampus plays a critical role in LTM formation [13]. We therefore performed a detailed gene expression analysis of genes related to glycogen metabolism following an IA task. Several genes related to both glycogen synthesis and degradation were modulated following IA learning. Fig 5 summarizes the modulation of glycogen metabolism related genes in the dorsal hippocampus across the different experimental conditions used in the study i.e. 3, 24 and 72 hours post-training (Fig 5A) and 3 hours after post-retention testing (Fig 5B). The dorsal hippocampus of the CS-US group demonstrated a 21 ± 8.3% increase of protein targeting to glycogen (PTG) mRNA as early as 3 hours post training. This induction persisted 24 hours post-training (18 ± 7.6%) as well as 3 hours post retention testing (9 ± 2.1%). However, this differential expression of PTG was lost 72 hours post-training (P> 0.05). We also observed a 16 ± 3.6% increase in hippocampal expression of glycogen branching enzyme 1 (Gbe1) in the CS-US group 3 hours post training, and this induction persisted both 24 hours (23 ± 4.5%) as well as 72 hours post-training (26 ± 3.3%). Furthermore, this up-regulation of Gbe1 was also seen at 3 hours post-retention testing (14 ± 4.3%). In addition, expression of phosphorylase b kinase (Phkb), which has a major regulatory role in the breakdown of glycogen was increased by 15 ± 5.7%, 24 hours post training and by 20 ± 5.5% 3 hours post-retention testing. Increased expression (31 ± 6%) of the muscle isoform of glycogen synthase (Gys1) that catalyzes the progressive extension of glycogen chain by adding successive glucose molecules was seen only at 24 hours post IA training but not at other time points (Fig 5). The expression of mRNA for other genes such as the brain isoform of glycogen phosphorylase (Pygb), responsible for glycogen degradation, did not differ across the two groups for all the tested time points (Fig 5).


Learning-Induced Gene Expression in the Hippocampus Reveals a Role of Neuron -Astrocyte Metabolic Coupling in Long Term Memory.

Tadi M, Allaman I, Lengacher S, Grenningloh G, Magistretti PJ - PLoS ONE (2015)

Glycogen regulation following IA learning.The table summarizes the changes seen in the mRNA expression of genes related to glycogen metabolism following IA task at 3, 24 or 72 hours after training (A) or 3 hours after testing (B). An upright arrow indicates significant induction of the gene in dorsal hippocampus of the CS-US group (P < 0.05, versus CS group, n = 7-8/group) whereas an upright arrow in brackets indicates an almost significant induction (i.e. P values very close to significance [P<0.05]) and a “-“entry indicates no significant difference across the two groups. Data were statistically analyzed using two-tailed Student’s t test. For abbreviations, see materials and methods section.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4625956&req=5

pone.0141568.g005: Glycogen regulation following IA learning.The table summarizes the changes seen in the mRNA expression of genes related to glycogen metabolism following IA task at 3, 24 or 72 hours after training (A) or 3 hours after testing (B). An upright arrow indicates significant induction of the gene in dorsal hippocampus of the CS-US group (P < 0.05, versus CS group, n = 7-8/group) whereas an upright arrow in brackets indicates an almost significant induction (i.e. P values very close to significance [P<0.05]) and a “-“entry indicates no significant difference across the two groups. Data were statistically analyzed using two-tailed Student’s t test. For abbreviations, see materials and methods section.
Mentions: Recently, we have shown that astrocytic glycogen metabolism in the hippocampus plays a critical role in LTM formation [13]. We therefore performed a detailed gene expression analysis of genes related to glycogen metabolism following an IA task. Several genes related to both glycogen synthesis and degradation were modulated following IA learning. Fig 5 summarizes the modulation of glycogen metabolism related genes in the dorsal hippocampus across the different experimental conditions used in the study i.e. 3, 24 and 72 hours post-training (Fig 5A) and 3 hours after post-retention testing (Fig 5B). The dorsal hippocampus of the CS-US group demonstrated a 21 ± 8.3% increase of protein targeting to glycogen (PTG) mRNA as early as 3 hours post training. This induction persisted 24 hours post-training (18 ± 7.6%) as well as 3 hours post retention testing (9 ± 2.1%). However, this differential expression of PTG was lost 72 hours post-training (P> 0.05). We also observed a 16 ± 3.6% increase in hippocampal expression of glycogen branching enzyme 1 (Gbe1) in the CS-US group 3 hours post training, and this induction persisted both 24 hours (23 ± 4.5%) as well as 72 hours post-training (26 ± 3.3%). Furthermore, this up-regulation of Gbe1 was also seen at 3 hours post-retention testing (14 ± 4.3%). In addition, expression of phosphorylase b kinase (Phkb), which has a major regulatory role in the breakdown of glycogen was increased by 15 ± 5.7%, 24 hours post training and by 20 ± 5.5% 3 hours post-retention testing. Increased expression (31 ± 6%) of the muscle isoform of glycogen synthase (Gys1) that catalyzes the progressive extension of glycogen chain by adding successive glucose molecules was seen only at 24 hours post IA training but not at other time points (Fig 5). The expression of mRNA for other genes such as the brain isoform of glycogen phosphorylase (Pygb), responsible for glycogen degradation, did not differ across the two groups for all the tested time points (Fig 5).

Bottom Line: The quantitative determination of mRNA levels revealed learning-induced changes in the expression of genes thought to be involved in astrocyte-neuron metabolic coupling in a time dependent manner.Twenty four hours following IA training, an enhanced gene expression was seen, particularly for genes encoding monocarboxylate transporters 1 and 4 (MCT1, MCT4), alpha2 subunit of the Na/K-ATPase and glucose transporter type 1.Together, these observations indicate that neuron-glia metabolic coupling undergoes metabolic adaptations following learning as indicated by the change in expression of key metabolic genes.

View Article: PubMed Central - PubMed

Affiliation: Brain Mind Institute, Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland.

ABSTRACT
We examined the expression of genes related to brain energy metabolism and particularly those encoding glia (astrocyte)-specific functions in the dorsal hippocampus subsequent to learning. Context-dependent avoidance behavior was tested in mice using the step-through Inhibitory Avoidance (IA) paradigm. Animals were sacrificed 3, 9, 24, or 72 hours after training or 3 hours after retention testing. The quantitative determination of mRNA levels revealed learning-induced changes in the expression of genes thought to be involved in astrocyte-neuron metabolic coupling in a time dependent manner. Twenty four hours following IA training, an enhanced gene expression was seen, particularly for genes encoding monocarboxylate transporters 1 and 4 (MCT1, MCT4), alpha2 subunit of the Na/K-ATPase and glucose transporter type 1. To assess the functional role for one of these genes in learning, we studied MCT1 deficient mice and found that they exhibit impaired memory in the inhibitory avoidance task. Together, these observations indicate that neuron-glia metabolic coupling undergoes metabolic adaptations following learning as indicated by the change in expression of key metabolic genes.

No MeSH data available.


Related in: MedlinePlus