Long-term functional recovery after facial nerve transection and repair in the rat

BACKGROUND: The rodent model is commonly used to study facial nerve injury. Because of the exceptional regenerative capacity of the rodent facial nerve, it is essential to consider the timing when studying facial nerve regeneration and functional recovery. Short-term functional recovery data following transection and repair of the facial nerve has been documented by our laboratory. However, because of the limitations of the head fixation device, there is a lack of long-term data following facial nerve injury. The objective of this study was to elucidate the long-term time course and functional deficit following facial nerve transection and repair in a rodent model. METHODS: Adult rats were divided into group 1 (controls) and group 2 (experimental). Group 1 animals underwent head fixation, followed by a facial nerve injury, and functional testing was performed from day 7 to day 70. Group 2 animals underwent facial nerve injury, followed by delayed head fixation, and then underwent functional testing from months 6 to 8. RESULTS: There was no statistical difference between the average whisking amplitudes in group 1 and group 2 animals. CONCLUSION: Functional whisking recovery 6 months after facial nerve injury is comparable to recovery within 1 to 4 months of transection and repair, thus the ideal window for evaluating facial nerve recovery falls within the 4 months after injury

Elevated basal serum tryptase identifies a multisystem disorder associated with increased TPSAB1 copy number

Elevated basal serum tryptase levels are present in 4-6% of the general population, but the cause and relevance of such increases are unknown. Previously, we described subjects with dominantly inherited elevated basal serum tryptase levels associated with multisystem complaints including cutaneous flushing and pruritus, dysautonomia, functional gastrointestinal symptoms, chronic pain, and connective tissue abnormalities, including joint hypermobility. Here we report the identification of germline duplications and triplications in the TPSAB1 gene encoding α-tryptase that segregate with inherited increases in basal serum tryptase levels in 35 families presenting with associated multisystem complaints. Individuals harboring alleles encoding three copies of α-tryptase had higher basal serum levels of tryptase and were more symptomatic than those with alleles encoding two copies, suggesting a gene-dose effect. Further, we found in two additional cohorts (172 individuals) that elevated basal serum tryptase levels were exclusively associated with duplication of α-tryptase-encoding sequence in TPSAB1, and affected individuals reported symptom complexes seen in our initial familial cohort. Thus, our findings link duplications in TPSAB1 with irritable bowel syndrome, cutaneous complaints, connective tissue abnormalities, and dysautonomia

New insights into the genetic etiology of Alzheimer’s disease and related dementias

Characterization of the genetic landscape of Alzheimer’s disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/‘proxy’ AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele