Lipids (phospholipids, cholesterol, sphingolipids, ceramides, triglycerides, fatty acids, and others) play vital roles as the major building blocks of cell membranes and in energy metabolism, and cell signaling. University of Alberta cell biologist Maria Ioannou is using cutting-edge cell imaging and biochemistry technologies to elucidate how lipids are moved within and between cells, and how those processes are involved in normal brain functions and if and how those processes are altered in neurodegenerative disorders such as Alzheimer's and Parkinson's disease. She discovered that when neurons are subjected to oxidative stress they accumulate oxidized potentially toxic lipids which are then extruded from the neurons in vesicles which are subsequently internalized by adjacent astrocytes thereby preventing damage to the neurons. Apolipoprotein E (ApoE) genotype is a major risk factor for Alzheimer's disease with ApoE4 increasing risk and ApoE2 and ApoE3 decreasing risk. Maria's laboratory provided evidence that the protective ApoEs enhance removal of toxic lipids from neurons wherease ApoE4 exacerbates accumulation of the toxic lipids in neurons Recently her lab provided that excessive accumulation of the lipid glucosylceramide in neurons results in the release of pathological alpha-synuclein in ectosomes which then transfer the alpha-synuclein to adjacent neurons. These finding may help explain how the neurodegenerative process spreads through neural networks in Parkinson's disease.

LINKS

Ioannou laboratory webpage:

https://ioannoulab.com/

Neuron-Astrocyte Metabolic Coupling Protects against Activity-Induced Fatty Acid Toxicity

https://www.cell.com/action/showPdf?pii=S0092-8674%2819%2930387-3

Protective ApoE variants support neuronal function by effluxing oxidized phospholipids:

https://www.cell.com/action/showPdf?pii=S0896-6273%2825%2900847-5

Glucosylceramide-induced ectosomes propagate pathogenic α-synuclein in Parkinson's disease:

file:///Users/markmattson/Downloads/s41556-026-01871-6%20(1).pdf

Interoception is a term used to describe the processes by which the brain detects, interprets, and responds adaptively to signals (pain, hunger, fatigue, etc.) coming from various organs in the body. In this episode University of Pennsylvania neuroscientist Nick Betley talks about recent research that has revealed key roles for relatively small numbers of neurons in the hypothalamus in interoception. Using cutting-edge imaging and molecular genetic tools Betley and his colleagues have shown how specific hypothalamic neurons can turn off pain signals and suppress inflammation. These findings have important implications for the development of interventions that alleviate chronic pain Intriguingly, they recently discovered that activation of a group of hypothalamic neurons (SF1 neurons) occurs in response exercise and their activation is required for endurance to increase with training. These findings suggest enhancement of hypothalamic SF1 neuron activity might prevent muscle loss during aging or in certain diseases or physical disabilities.

LINKS
Betley laboratory page:

https://web.sas.upenn.edu/betley-lab/

Exercise-induced activation of ventromedial hypothalamic steroidogenic factor-1 neurons mediates improvements in endurance.

https://www.cell.com/action/showPdf?pii=S0896-6273%2825%2900989-4

Anti-inflammatory effects of hunger are transmitted to the periphery via projection-specific AgRP circuits.

https://www.cell.com/action/showPdf?pii=S2211-1247%2823%2901350-5

A Neural Circuit for the Suppression of Pain by a Competing Need State.

https://www.cell.com/action/showPdf?pii=S0092-8674%2818%2930234-4

Normally activity in the brain's neural networks is tightly regulated by the interplay between neuronal excitation by the neurotransmitter glutamate and inhibition by GABA. An epileptic seizure is a dramatic example of what can happen when an abrupt excitatory imbalance occurs. However, excitatory imbalances also occur during aging and contribute to the dysfunction and degeneration of neurons in Alzheimer's disease. In this episode I talk with University of Washington Associate Professor Melissa Barker-Haliski about how neural network activity is normally regulated, the causes of hyperexcitability in neurological disorders, and the benefits and pitfalls of drugs that suppress neural network excitability.

LINKS

Barker-Haliski lab page:

https://sites.uw.edu/mhaliski/

Review articles:

https://pmc.ncbi.nlm.nih.gov/articles/PMC11390315/pdf/nihms-2013484.pdf

https://pmc.ncbi.nlm.nih.gov/articles/PMC9096090/pdf/fneur-13-833624.pdf

Original research articles:

https://www.sciencedirect.com/science/article/pii/S0014488625004510?via%3Dihub

https://journals.sagepub.com/doi/epub/10.1177/13872877251343321

https://onlinelibrary.wiley.com/doi/epdf/10.1111/epi.18395?saml_referrer