Positron Emission Tomography reveals age-associated hypothalamic microglial activation in women.

In rodents, hypothalamic inflammation plays a critical role in aging and age-related diseases. Hypothalamic inflammation has not previously been assessed in vivo in humans. We used Positron Emission Tomography (PET) with a radiotracer sensitive to the translocator protein (TSPO) expressed by activated microglia, to assess correlations between age and regional brain TSPO in a group of healthy subjects (n = 43, 19 female, aged 23-78), focusing on hypothalamus. We found robust age-correlated TSPO expression in thalamus but not hypothalamus in the combined group of women and men. This pattern differs from what has been described in rodents. Prominent age-correlated TSPO expression in thalamus in humans, but in hypothalamus in rodents, could reflect evolutionary changes in size and function of thalamus versus hypothalamus, and may be relevant to the appropriateness of using rodents to model human aging. When examining TSPO PET results in women and men separately, we found that only women showed age-correlated hypothalamic TSPO expression. We suggest this novel result is relevant to understanding a stark sex difference in human aging: that only women undergo loss of fertility-menopause-at mid-life. Our finding of age-correlated hypothalamic inflammation in women could have implications for understanding and perhaps altering reproductive aging in women.

The roles of GnRH in the human central nervous system.

It is widely known that GnRH plays a role in facilitating reproductive function via the HPG axis, and this was once believed to be its only function. However, over the last several decades important neuromodulatory roles of GnRH in multiple brain functions have been elucidated. Multiple GnRH isoforms and receptors have been detected outside the HPG-axis across different species. In this review, we focus on the human CNS where GnRH I and II isoforms and a functional GnRH I receptor have been isolated. We first describe the traditional understanding of GnRH within the hypothalamus and the pituitary and current clinical use of GnRH analogues. We then review the location and function of GnRH-producing neurons and receptors located outside the HPG axis. We next review the GnRH I and II neuron location and quantity and GnRH I receptor gene expression throughout the human brain, using the Allen Brain Map Atlas. This analysis demonstrates a wide expression of GnRH throughout the brain, including prominent expression in the basal forebrain and cerebellum. Lastly, we examine the potential role of GnRH in aging and inflammation and its therapeutic potential for neurodegenerative disease and spinal cord lesions.

Tau PET following acute TBI: Off-target binding to blood products, tauopathy, or both?

Repeated mild Traumatic Brain Injury (TBI) is a risk factor for Chronic Traumatic Encephalopathy (CTE), characterized pathologically by neurofibrillary tau deposition in the depths of brain sulci and surrounding blood vessels. The mechanism by which TBI leads to CTE remains unknown but has been posited to relate to axonal shear injury leading to release and possibly deposition of tau at the time of injury. As part of an IRB-approved study designed to learn how processes occurring acutely after TBI may predict later proteinopathy and neurodegeneration, we performed tau PET using 18F-MK6240 and MRI within 14 days of complicated mild TBI in three subjects. PET radiotracer accumulation was apparent in regions of traumatic hemorrhage in all subjects, with prominent intraparenchymal PET signal in one young subject with a history of repeated sports-related concussions. These results are consistent with off-target tracer binding to blood products as well as possible on-target binding to chronically and/or acutely-deposited neurofibrillary tau. Both explanations are highly relevant to applying tau PET to understanding TBI and CTE. Additional study is needed to assess the potential utility of tau PET in understanding how processes occurring acutely after TBI, such as release and deposition of tau and blood from damaged axons and blood vessels, may relate to development CTE years later.

Acute Hepatitis A Outbreak Among Men Who Have Sex With Men in Krakow, Poland; February 2017-February 2018.

Since February 2017 in Poland, an increasing number of acute hepatitis A (AHA) cases have been reported; a noteworthy increase to 3,072 cases of AHA in 2017 compared to 35 cases in 2016 was reported by the National Institute of Public Health (NIPH). The aim of this study was to evaluate the demographic features, clinical manifestations, laboratory results, and sexually transmitted coinfections. All cases of AHA diagnosed between February 2017 and February 2018 at the University Hospital in Krakow were analyzed. A total of 119 cases of hepatitis A virus (HAV) were reported; 105 (88%) were males and 14 (12%) were females, with a mean age 31 years (range 19-62). In 84 patients (71%), the HAV was transmitted by oral-anal sexual contact between men. Six women were infected by close house contact with men infected with HAV. The route of transmission was not identified for 29 cases, and 88 patients (74%) required hospitalization. Among the cases, the following coinfections were already diagnosed: HIV 36 patients (30%), chronic hepatitis C virus (HCV) 4 patients (3%), and chronic hepatitis B virus (HBV) 2 patients (1.5%). During AHA diagnosis, some new sexually transmitted infections (STIs) were detected; syphilis eight patients (6.7%), HIV/syphilis seven patients (6%), HIV//HCV/syphilis one patient, and acute retroviral syndrome/Shigella flexneri one patient. Overall, AHA outbreak in Poland in 2017 affected primarily men who have sex with men (MSM) and was connected with oral-anal sexual contacts, and the majority of patients did not have HAV vaccination. These results show a clear need for routinely offering HAV vaccination to at-risk populations and that awareness among health-care workers about HAV sexual transmission may help introduce prevention methods.