A recent study has made a significant breakthrough in understanding the mechanisms behind migraine headaches. It revealed the pivotal role of specific mouse models provided by the Mutant Mouse Resource & Research Centers (MMRRC). This research identifies the PACAP38-MrgprB2 pathway as a crucial factor in stress-induced migraine.

Study Overview

Migraine headaches, affecting approximately 15% of the global population, remain a poorly understood yet highly disruptive condition. Researchers have now demonstrated that increased pituitary adenylate cyclase-activating polypeptide-38 (PACAP38) due to stress can induce headache-like behaviors in mice. This discovery sheds light on how migraines may serve as a warning signal for stress-induced homeostatic imbalances.

Methodology and Key Findings

The study utilized PAC1 conditional knockout (KO) mice, generated by crossing C57BL/6N-Atm1BrdAdcyap1r1tm1a(KOMP)Wtsi/MbpMmucd mice (MMRRC #46,500) with B6N(B6J)-Tg(CAG-Flpo)1Afst/Mmucd mice (MMRRC #36,512). These mice were essential in investigating the PACAP38-MrgprB2 pathway.

Researchers found that increased levels of PACAP38, resulting from repetitive stress, caused MrgprB2-dependent headache behaviors. This effect was mediated by mast cell degranulation, which sensitized trigeminal ganglion neurons. Blocking this pathway successfully prevented the development of headache behaviors in the mice.

Implications for Migraine Treatment

This study highlights the PACAP38-MrgprB2 pathway as a promising target for new migraine treatments, particularly stress-related ones. Understanding this pathway provides critical insights into the biological mechanisms that cause migraines and opens new avenues for therapeutic development.

Source: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11131290/

MMRRC Mice Used:

https://www.mmrrc.org/catalog/sds.php?mmrrc_id=45000

https://www.mmrrc.org/catalog/sds.php?mmrrc_id=36512

In groundbreaking research, scientists have elucidated the effects of neuroinflammation on brain metabolism in Alzheimer's disease using the APPswe/PS1dE9 mouse model (MMRRC Strain # 034829). This study promises to enhance early diagnostic methods and the development of targeted treatments.

Methodology

Employing in vivo 2-photon microscopy alongside the Oxyphor 2P oxygen sensor, the team measured oxygen levels and capillary blood flow in the brains of mice before and after inducing neuroinflammation with lipopolysaccharide (LPS). Initially, Alzheimer's mice exhibited a lower metabolic demand than healthy counterparts, with similar capillary blood flow across both groups.

Results

After the LPS treatment, both groups showed significant decreases in oxygen levels with increased oxygen extraction, while capillary flow remained stable. These findings suggest that neuroinflammation primarily affects brain metabolism rather than blood flow, underlining its potential as a target for early intervention in Alzheimer's progression.

Broader Implications

The implications of this study extend beyond Alzheimer's disease, potentially offering insights into other conditions where neuroinflammation affects cognitive functions. This research underscores the importance of targeting inflammation in early therapeutic strategies and invites further investigation into the complex interactions between neuroinflammation and cerebral energetics.

References

Paper Source: 10.1186/s13195-024-01444-5
Mouse Model: APPswe/PS1dE9


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Welcome to the Mutant Mouse Resource & Research Centers (MMRRC) Website

The MMRRC is the nation’s premier national public repository system for mutant mice. Funded by the NIH continuously since 1999, the MMRRC archives and distributes scientifically valuable spontaneous and induced mutant mouse strains and ES cell lines for use by the biomedical research community. The MMRRC consists of a national network of breeding and distribution repositories and an Informatics Coordination and Service Center located at 4 major academic centers across the nation. The MMRRC is committed to upholding the highest standards of experimental design and quality control to optimize the reproducibility of research studies using mutant mice. The MMRRC is supported by the Office of Research Infrastructure Programs (ORIP) in the Office of the Director at NIH. More than 60,000 mutant alleles are maintained as live mice, cryopreserved germplasm, and/or mutant ES cells. Live mice are supplied from a production colony, from a colony recovered from cryopreservation, or via micro-injection of ES cells. An MMRRC facility may offer cryopreserved material for resuscitation at the recipient scientist's institution.