Isoflurane unveils a critical role of glutamate transporter type 3 in regulating hippocampal GluR1 trafficking and context-related learning and memory in mice

Thyroid hormones regulate brain development and function through the control of gene expression, mediated by binding of T3 to nuclear receptors. Brain T3 concentration is tightly controlled by homeostatic mechanisms regulating transport and metabolism of T4 and T3. We have examined the role of the inactivating enzyme type 3 deiodinase (D3) in the regulation of 43 thyroid hormone-dependent genes in the cerebral cortex of 30-d-old mice. D3 inactivation increased slightly the expression of two of 22 positively regulated genes and significantly decreased the expression of seven of 21 negatively regulated genes. Administration of high doses of T3 led to significant changes in the expression of 12 positive genes and three negative genes in wild-type mice. The response to T3 treatment was enhanced in D3-deficient mice, both in the number of genes and in the amplitude of the response, demonstrating the role of D3 in modulating T3 action. Comparison of the effects on gene expression observed in D3 deficiency with those in hypothyroidism, hyperthyroidism, and type 2 deiodinase (D2) deficiency revealed that the negative genes are more sensitive to D2 and D3 deficiencies than the positive genes. This observation indicates that, in normal physiological conditions, D2 and D3 play critical roles in maintaining local T3 concentrations within a very narrow range. It also suggests that negatively and positively regulated genes do not have the same physiological significance or that their regulation by thyroid hormone obeys different paradigms at the molecular or cellular levels.

Download Full-text

Critical role of an eight-amino acid sequence of VP1 in neutralization of poliovirus type 3

Nature ◽

10.1038/304459a0 ◽

1983 ◽

Vol 304 (5925) ◽

pp. 459-462 ◽

Cited By ~ 61

Author(s):

D. M. A. Evans ◽

P. D. Minor ◽

G. S. Schild ◽

J. W. Almond

Keyword(s):

Amino Acid ◽

Amino Acid Sequence ◽

Critical Role ◽

Poliovirus Type ◽

Type 3

Download Full-text

Monkey Perirhinal Cortex is Critical for Visual Memory, but not for Visual Perception: Reexamination of the Behavioural Evidence from Monkeys

The Quarterly Journal of Experimental Psychology Section B ◽

10.1080/02724990444000195 ◽

2005 ◽

Vol 58 (3-4b) ◽

pp. 283-299 ◽

Cited By ~ 40

Author(s):

Robert R. Hampton

Keyword(s):

Visual Perception ◽

Learning And Memory ◽

Discrimination Learning ◽

Visual Memory ◽

Critical Role ◽

Perirhinal Cortex ◽

Published Data ◽

Data Call ◽

Behavioural Evidence

Overdependence on discrimination learning paradigms to assess the function of perirhinal cortex has complicated understanding of the cognitive role of this structure. Impairments in discrimination learning can result from at least two distinct causes: (a) failure to accurately apprehend and represent the relevant stimuli, or (b) failure to form and remember associations between stimulus representations and reward. Thus, the results of discrimination learning experiments do not readily differentiate deficits in perception from deficits in learning and memory. Here I describe studies that do dissociate learning and memory from perception and show that perirhinal cortex damage impairs learning and/or memory, but not perception. Reanalysis and reconsideration of other published data call into further question the hypothesis that the monkey perirhinal cortex plays a critical role in visual perception.

Download Full-text

CD1d-Dependent iNKT Cells Control DSS-Induced Colitis in a Mouse Model of IFNγ-Mediated Hyperinflammation by Increasing IL22-Secreting ILC3 Cells

International Journal of Molecular Sciences ◽

10.3390/ijms22031250 ◽

2021 ◽

Vol 22 (3) ◽

pp. 1250

Author(s):

Hyun Jung Park ◽

Sung Won Lee ◽

Luc Van Kaer ◽

Seokmann Hong

Keyword(s):

Intestinal Inflammation ◽

Critical Role ◽

Lymphoid Cells ◽

Inkt Cell ◽

Mesenteric Lymph Nodes ◽

Inkt Cells ◽

Mesenteric Lymph ◽

Type 3

We have previously shown that CD1d-restricted iNKT cells suppress dysregulated IFNγ expression and intestinal inflammation in Yeti mice on the C57BL/6 background. Since type 3 innate lymphoid cells (ILC3s) in mesenteric lymph nodes (MLN) protect against intestinal inflammation in a CD1d-associated manner, we investigated whether crosstalk between iNKT cells and MLN ILC3s controls IFNγ-mediated intestinal inflammation in Yeti mice. We found that Yeti mice display increased levels of ILC3s and that iNKT cell deficiency in Yeti/CD1d KO mice decreases levels of IL22-producing ILC3s during DSS-induced colitis. This finding indicates that iNKT cells and ILC3s cooperate to regulate intestinal inflammation in Yeti mice. Yeti iNKT cells displayed a pronounced anti-inflammatory (IL4- or IL9-producing) phenotype during colitis. Their adoptive transfer to iNKT cell-deficient animals induced a significant increase in IL22 production by ILC3s, indicating that crosstalk between iNKT cells and ILC3s plays a critical role in modulating colitis in Yeti mice. Moreover, we showed that the IL9-producing subset of iNKT cells potently enhances IL22-producing ILC3s in vivo. Taken together, our results identify a central role of the iNKT cell-ILC3 axis in ameliorating IFNγ-mediated intestinal inflammation.

Download Full-text