Selected Grantee Publications
- Clear All
- 4 results found
- nimh
- Alzheimer's Disease
- Microbiome
Senescent-like Microglia Limit Remyelination Through the Senescence Associated Secretory Phenotype
Gross et al., Nature Communications. 2025.
https://www.nature.com/articles/s41467-025-57632-w
Multiple sclerosis (MS) is a chronic, immune-mediated demyelinating disease in which immune cells infiltrate the central nervous system and promote deterioration of myelin and neurodegeneration. The capacity to regenerate myelin in the central nervous system diminishes with age. In this study, researchers used 2- to 3-month-old (young), 12-month-old (middle-aged), and 18- to 22-month-old (aged) C57BL/6 male and female mice. Results showed an upregulation of the senescence marker P16ink4a (P16) in microglial and macrophage cells within demyelinated lesions. Notably, treatment of senescent cells using genetic and pharmacological senolytic methods leads to enhanced remyelination in young and middle-aged mice but fails to improve remyelination in aged mice. These results suggest that therapeutic targeting of senescence-associated secretory phenotype components may improve remyelination in aging and MS. Supported by ORIP (R24OD036199), NIA, NINDS, and NIMH.
Sociability in a Non-Captive Macaque Population Is Associated with Beneficial Gut Bacteria
Johnson et al., Frontiers in Microbiology. 2022.
https://www.doi.org/10.3389/fmicb.2022.1032495
Social connections are essential for good health and well-being in social animals, such as humans and other primates. Increasingly, evidence suggests that the gut microbiome—through the so-called “gut–brain axis”—plays a key role in physical and mental health and that bacteria can be transmitted socially (e.g., through touch). Here, the authors explore behavioral variation in non‑captive rhesus macaques of both sexes with respect to the abundance of specific bacterial genera. Their results indicate that microorganisms whose abundance varies with individual social behavior also have functional links to host immune status. Overall, these findings highlight the connections between social behavior, microbiome composition, and health in an animal population. Supported by ORIP (P40OD012217) and NIMH.
Reduced Alcohol Preference and Intake after Fecal Transplant in Patients with Alcohol Use Disorder Is Transmissible to Germ-Free Mice
Wolstenholme et al., Nature Communications. 2022.
https://www.doi.org/10.1038/s41467-022-34054-6
Alcohol use disorder is a major cause of reduced life expectancy worldwide, and this misuse has increased exponentially during the COVID-19 pandemic. Fecal microbiota transplant has been shown previously to reduce alcohol craving in humans with cirrhosis. Here, the investigators report that the reduction in craving and alcohol preference is transmissible to male germ-free mice only when live bacteria—and not germ-free supernatants—are used for colonization. This differential colonization was associated with alterations in the gut immune–inflammatory response through short-chain fatty acids. Supported by ORIP (P40OD010995), NIAAA, NIDDK, and NIMH.
Cannabinoid Control of Gingival Immune Activation in Chronically SIV-Infected Rhesus Macaques Involves Modulation of the Indoleamine-2,3-Dioxygenase-1 Pathway and Salivary Microbiome
McDew-White et al., EBioMedicine. 2021.
https://pubmed.ncbi.nlm.nih.gov/34954656/
HIV-associated periodontal disease (PD) affects people living with HIV (PLWH) on combination anti-retroviral therapy (cART). Researchers used a systems biology approach to investigate the molecular, metabolome, and microbiome changes underlying PD and its modulation by phytocannabinoids (Δ9-THC) in rhesus macaques. Δ9-THC reduced IDO1 protein expression. The findings suggest that phytocannabinoids may help reduce gingival/systemic inflammation, salivary dysbiosis, and potentially metabolic disease in PLWH on cART. Supported by ORIP (P51OD011104, P51OD011133, U42OD010442), NIAID, NIDA, NIDDK, NIDCR, and NIMH.