A team of researchers at Kyoto University recently set out to understand the mechanisms behind which two-hit stress contributes to brain dysfunction and mental disorders. They conducted a comprehensive investigation of the social and cognitive behaviors of mice that have been exposed to such stress, paying particular attention to anxiety-like behaviors.

Previously, this team demonstrated that acute inflammation in the cerebellum caused by a bacterial infection induces neural plasticity, which in turn may lead to hyper-excitability in the brain and the onset of depressive and autism-like symptoms. Yet exactly how two-hit stress contributes to changes in the brain had remained unclear.

Subject mice in the current investigation were allowed to freely explore, revealing extensive behavioral differences in two-hit mice, correlating with abnormalities in the cerebellum. In particular, the researchers observed a significant increase in the number and turnover of microglia, the primary immune cells found in the central nervous system. The study also revealed neuronal loss in the cerebellum, a reduction in the action potential firing of remaining cerebellar neurons, and a decrease in brain-wide functional connectivity.

“These results indicate cerebellar cognitive dysfunctions in animals exposed to two-hit stress,” says team member Momoka Hikosaka. The exposure to such stress altered the microglial reactivity in the cerebella of both male and female mice, leading to cerebellar dysfunction and behaviors resembling psychiatric disorders.

But it’s not all bad news. To rescue the exposed mice, the researchers used microglia replacement to ameliorate the effects of two-hit stress. Suppressing microglia can also be effective, but systemic depletion of microglia typically weakens immunity, making the body more susceptible to infections.

“To address this limitation, our team performed cerebellum-specific microglia replacement, which worked remarkably well,” says corresponding author Gen Ohtsuki, adding, “We were impressed to observe that the female mice showed notably higher stress resilience.”

This suggests that in some animals, sex differences in response to chronic inflammatory stress emerge in the cerebellum under certain conditions. Consequently, personalized medicine for mental health may require considering sex differences as an important factor, which could also be applied to neurodegenerative diseases and aging treatment.

Overall, these findings provide new pathways for understanding the biological mechanisms behind mental disorders, and have the potential to transform both scientific approaches and societal attitudes toward helping those affected.

Associate Professor Stephen Howie from the University’s Faculty of Medical and Health Sciences (FMHS) was an adviser to the Lancet Global Health Commission on Medical Oxygen Security and co-author of its report Reducing global inequities in medical oxygen access released 18 February.

A key finding shows global access to medical oxygen is highly inequitable. Five billion people, mostly from low and middle-income countries don’t have access to safe, quality, affordable medical oxygen.

Associate Professor Howie, child health researcher and a specialist paediatrician says he hopes further lives will be saved because of this work, and that children and adults will not only survive but thrive.

The Auckland University team are leading the field to improve access to medical oxygen. Howie recently gave a plenary address at the World Lung Health Conference in Bali, spelling out the challenges and opportunities to tackle the global issue.

“I have been working in the area of oxygen treatment for oxygen-starved (hypoxic) illnesses for two decades, particularly in Africa and the Pacific. My first priority was children (naturally, as a paediatrician) but we learnt soon enough that solving the problem has to involve catering for all ages.

“It is such an obvious need. I saw it at the hospitals I worked at in Africa where needless death from diseases like pneumonia happened because oxygen supplies were short, and this hit families and staff very hard. It was at that time that we made it our goal that ‘no child should die for lack of oxygen’ and this applies to adults too.”

Fiji was particularly hard hit when the first waves of the COVID-19 pandemic arrived, at one point it had the highest rate of COVID-19 in the world. A close partnership between the Fiji Ministry of Health, the University of Auckland, Cure Kids and Fiji National University, funded by New Zealand MFAT and other donors, played an important role in supporting the pandemic response says Howie.

A team of researchers from the School of Biological Sciences, The University of Hong Kong (HKU), addressed these questions in a recent paper in the Proceedings of the National Academy of Sciences (PNAS), USA, by compiling information on nearly 15,000 funded projects focused on species conservation. Professor Benoit GUÉNARD, the lead author of the study, noted that, “Our first conclusion is that funding for species conservation research remains extremely limited with only US$ 1.93 billion allocated over 25 years in the projects we assessed.”

The international conservation funding from 37 governments and NGOs represented a mere 0.3% and 0.01% of the annual budget of the NASA or US military, respectively. This stark comparison underscores the urgent need to dramatically increase such funding to slow global biodiversity loss.

The authors also examined the allocation of this funding to specific species or groups of organisms based on their conservation needs as assessed by the International Union for Conservation of Nature (IUCN) Red List, often called the ‘barometer of life’. Professor Guénard explains, “Based on previous literature-based studies, we expected biases towards vertebrates and, whilst this was true, we found the situation much worse than previously estimated. Even within vertebrates, many of the most threatened groups, like amphibians, were largely underfunded with declining funding trends over time.”

Another striking example can be found in reptiles, particularly lizards and snakes, where over a thousand species have been identified as threatened, yet 87% of the funding towards reptile conservation is directed towards the seven species of marine turtles. Professor Guénard states, “This highlights an important mismatch between scientific assessment of conservation and allocation of funding by conservation stakeholders, which appears to rely on the ‘charisma’ of species. This leads to nearly a third of the funding directed to non-threatened species while almost 94% of threatened species have not received any support.”

Some groups, like plants or insects, received a mere 6% each of the funding despite their vast diversity and the number of threatened species they include, while other major groups, such as fungi or algae, received virtually no funding.

Professor Alice HUGHES, a co-author of the study, echoed, “Our traditional view of what is threatened often does not align with species genuinely at threat, leaving many smaller, or ‘less charismatic’ species neglected. We urgently need to reframe this perspective and better allocate funding across taxa if we want any hope of redressing widespread population declines and the continued loss of biodiversity.”

Based on these findings, the researchers are calling for a new approach to conservation funding. Whilst species conservation is in dire need of additional funding, a more rigorous approach to selecting projects and species to receive those limited funds is urgently needed. Professor Guénard emphasises, “Conservation agencies and NGOs need to modify their philosophy towards conservation to protect all species, and not just a subset based on subjective criteria of charisma or beauty.”

In the future, the research team hopes their database can be expanded so information on funding allocation is more transparent and easily accessible. This would help evaluate existing gaps, plan effective future conservation efforts at a global scale, and reduce redundancy in funding for species that already receive the lion’s share of support.