Tag: poly I:C

Development of a Mouse Model for Chronic Fatigue Syndrome

Abstract:

The purpose of this study was to develop a clinically relevant mouse model of CFS to allow for the testing of underlying mechanisms and development of novel treatment interventions.

Mice were injected with either lipopolysaccharide (LPS) or Poly I:C systemically (0.1- 1.0 mg/kg LPS, i.p. or 0.6-6mg/kg Poly I:C) and compared to a vehicle control injection.

To test for fatigue-like behaviors, we examined voluntary wheel running (VWR) and open field activity.

To test for pain-like behaviors, muscle withdrawal thresholds (MWT) and mechanical sensitivity of the paw.

Measurements were assessed before and up to 1 week after injection of LPS or Poly I:C.

Differences in voluntary running wheel data were assessed using mixed model analysis for differences between dose, time and an interaction between dose and time.

Differences in open field parameters, MWT, and paw sensitivity between groups were assessed using repeated measures ANOVAs.

Running wheel activity was reduced after injection of either LPS or Poly I:C (χ2=15.4; p=0.003).

LPS reduced running wheel activity on days 1-3 for the 1.0 mg/kg dose of LPS and on Day 1 for Poly I:C when compared to vehicle (p<0.001).

Lower doses of LPS showed faster recovery to baseline.

For the open field testing, LPS reduced in distance travelled (F=9.1; p<0.001), increase in time standing still (F=6.5, p=0.001) but not time in center (F= 1.1, p=0.36) 24h after infection.

Post-hoc testing (Tukey’s test) showed a significant difference between the vehicle and the 1.0 mg/kg group of LPS (p=0.001).

Similar reductions were observed for the 6 mg/kg group of Poly I:C (p<0.001). For pain behaviors, there was no difference between groups in the MWT or paw sensitivity (p>0.05) for either LPS or Poly I:C.

These results show that a single injection of an infectious agent reduces physical activity and exploratory behavior, but does not produce pain behaviors.

Source: Adam Janowski, Joseph Lesnak, Ashley Plumb, Lynn Rasmussen, Kathleen Sluka. Development of a Mouse Model for Chronic Fatigue Syndrome. The Journal of Pain 23 (5): 12. https://www.sciencedirect.com/science/article/abs/pii/S152659002200092X

An Adrenalectomy Mouse Model Reflecting Clinical Features for Chronic Fatigue Syndrome

Abstract:

Chronic fatigue syndrome (CFS) is one of the most intractable diseases and is characterized by severe central fatigue that impairs even daily activity. To date, the pathophysiological mechanisms are uncertain and no therapies exist. Therefore, a proper animal model reflecting the clinical features of CFS is urgently required.

We compared two CFS animal models most commonly used, by injection with lipopolysaccharide (LPS from Escherichia coli O111:B4) or polyinosinic: polycytidylic acid (poly I:C), along with bilateral adrenalectomy (ADX) as another possible model. Both LPS- and poly I:C-injected mice dominantly showed depressive behaviors, while ADX led to fatigue-like performances with high pain sensitivity.

In brain tissues, LPS injection notably activated microglia and the 5-hydroxytryptamine (HT)1A receptor in the prefrontal cortex and hippocampus. Poly I:C-injection also remarkably activated the 5-HT transporter and 5-HT1A receptor with a reduction in serotonin levels in the brain. ADX particularly activated astrocytes and transforming growth factor beta (TGF-β) 1 in all brain regions.

Our results revealed that LPS and poly I:C animal models approximate depressive disorder more closely than CFS. We suggest that ADX is a possible method for establishing a mouse model of CFS reflecting clinical features, especially in neuroendocrine system.

Source: Lee JS, Jeon YJ, Park SY, Son CG. An Adrenalectomy Mouse Model Reflecting Clinical Features for Chronic Fatigue Syndrome. Biomolecules. 2020 Jan 1;10(1). pii: E71. doi: 10.3390/biom10010071. https://www.mdpi.com/2218-273X/10/1/71 (Full article)