Rat bite fever on Vancouver Island: 2010-2016.

BACKGROUND: Rat bite fever (RBF) is a rare bacterial zoonotic infection caused by Streptobacillus moniliformis and Spirillum minus, which are found naturally in rodent respiratory tracts. Recently, multiple cases of RBF were observed on Vancouver Island, British Columbia. OBJECTIVE: To conduct a case series analysis of cases of RBF on Vancouver Island between 2010 and 2016 to characterize the epidemiology, presentation, microbiology and treatment of RBF. METHODS: Cases were identified through queries of discharge diagnosis and microbiology laboratory information. Clinical details were collected through review of electronic and paper chart reviews of hospital documentation from Island Health. RESULTS: Eleven cases of RBF on Vancouver Island were identified between 2010 and 2016. Most cases of RBF were confirmed with identification of S. moniliformis by culture or molecular techniques. All cases presented with fever, and a subset had one or more of the following: myalgia, rash, polyarthralgia, joint effusions, and emesis. All cases were successfully treated with penicillin, ceftriaxone or doxycycline. Seven cases required hospitalization, but there were no deaths or significant morbidity. CONCLUSION: This is the largest single case series of RBF in Canada. Diagnosis requires a high index of suspicion by clinicians and early intervention is necessary to prevent morbidity and mortality.

Impaired bidirectional NMDA receptor dependent synaptic plasticity in the dentate gyrus of adult female Fmr1 heterozygous knockout mice.

Fragile-X syndrome (FXS) is caused by the transcriptional repression of the Fmr1 gene resulting in loss of the Fragile-X mental retardation protein (FMRP). This leads to cognitive impairment in both male and female patients, however few studies have focused on the impact of FXS in females. Significant cognitive impairment has been reported in approximately 35% of women who exhibit a heterozygous Fmr1 gene mutation, however to date there is a paucity of information regarding the mechanistic underpinnings of these deficits. We, and others, have recently reported that there is significant impairment in N-methyl-d-aspartate receptor (NMDAR)-dependent long-term potentiation (LTP) and long-term depression (LTD) in the hippocampal dentate gyrus (DG) of male Fmr1 knock out mice. Here we examined if female mice displaying a heterozygous loss of the Fmr1 gene (Fmr1+/-) would exhibit similar impairments in DG-dependent spatial memory processing and NMDAR hypofunction. We found that Female Fmr1+/- mice did not show impaired metabotropic glutamate receptor (mGluR)-LTD in the CA1 region, and could perform well on a temporal ordering task that is thought to involve this brain region. In contrast, female Fmr1+/- mice showed impairments in a pattern separation task thought to involve the DG, and also displayed a significant impairment in both NMDAR-dependent LTD and LTP in this region. The LTP impairment could be rescued by administering the NMDAR co-agonist, glycine. Our data suggests that NMDAR hypofunction in the DG may partly contribute to learning and memory impairment in female Fmr1+/- mice. Targeting NMDAR-dependent mechanisms may offer hope as a new therapeutic approach for treating female FXS patients with learning and memory impairments.

Enhanced corticosteroid signaling alters synaptic plasticity in the dentate gyrus in mice lacking the fragile X mental retardation protein.

The fragile X mental retardation protein (FMRP) is an important regulator of protein translation, and a lack of FMRP expression leads to a cognitive disorder known as fragile X syndrome (FXS). Clinical symptoms characterizing FXS include learning impairments and heightened anxiety in response to stressful situations. Here, we report that, in response to acute stress, mice lacking FMRP show a faster elevation of corticosterone and a more immediate impairment in N-methyl-d-aspartate receptor (NMDAR) dependent long-term potentiation (LTP) in the dentate gyrus (DG). These stress-induced LTP impairments were rescued by administering the glucocorticoid receptor (GR) antagonist RU38486. Administration of RU38486 also enhanced LTP in Fmr1(-/y) mice in the absence of acute stress to wild-type levels, and this enhancement was blocked by application of the NMDAR antagonist 2-amino-5-phosphonopentanoic acid. These results suggest that a loss of FMPR results in enhanced GR signaling that may adversely affect NMDAR dependent synaptic plasticity in the DG.