Lifeboat Foundation

Just as a conductor coordinates different instruments in an orchestra to produce a symphony, breathing coordinates hippocampal brain waves to strengthen memory while we sleep, reports a new Northwestern Medicine study.

This is the first time breathing rhythms during sleep have been linked to these hippocampal brain waves—called slow waves, spindles and ripples—in humans. Scientists knew these waves were linked to memory but their underlying driver was unknown. The study is published in the Proceedings of the National Academy of Sciences.

“To strengthen memories, three special neural oscillations emerge and synchronize in the hippocampus during sleep, but they were thought to come and go at random times,” said senior study author Christina Zelano, professor of neurology at Northwestern University Feinberg School of Medicine. “We discovered that they are coordinated by breathing rhythms.”

Glyphosate use in the United States (US) has increased each year since the introduction of glyphosate-tolerant crops in 1996, yet little is known about its effects on the brain. We recently found that C57BL/6J mice dosed with glyphosate for 14 days showed glyphosate and its major metabolite aminomethylphosphonic acid present in brain tissue, with corresponding increases in pro-inflammatory cytokine tumor necrosis factor-⍺ (TNF-⍺) in the brain and peripheral blood plasma. Since TNF-⍺ is elevated in neurodegenerative disorders such as Alzheimer’s Disease (AD), in this study, we asked whether glyphosate exposure serves as an accelerant of AD pathogenesis. Additionally, whether glyphosate and aminomethylphosphonic acid remain in the brain after a recovery period has yet to be examined.

We hypothesized that glyphosate exposure would induce neuroinflammation in control mice, while exacerbating neuroinflammation in AD mice, causing elevated Amyloid-β and tau pathology and worsening spatial cognition after recovery. We dosed 4.5-month-old 3xTg-AD and non-transgenic (NonTg) control mice with either 0, 50 or 500 mg/kg of glyphosate daily for 13 weeks followed by a 6-month recovery period.

We found that aminomethylphosphonic acid was detectable in the brains of 3xTg-AD and NonTg glyphosate-dosed mice despite the 6-month recovery. Glyphosate-dosed 3xTg-AD mice showed reduced survival, increased thigmotaxia in the Morris water maze, significant increases in the beta secretase enzyme (BACE-1) of amyloidogenic processing, amyloid-β (Aβ) 42 insoluble fractions, Aβ 42 plaque load and plaque size, and phosphorylated tau (pTau) at epitopes Threonine 181, Serine 396, and AT8 (Serine 202, Threonine 205). Notably, we found increased pro-and anti-inflammatory cytokines and chemokines persisting in both 3xTg-AD and NonTg brain tissue and in 3xTg-AD peripheral blood plasma.

As humans, we have the ability to recall detailed information, even from years in the past, indicating a powerful memory system. Newly encoded explicit memories initially depend on the hippocampus^1,2,3,4. Memory reactivation, mediated by a hippocampo-cortical dialog, leads to a gradual maturation of neocortical engrams over time^5,6,7,8,9. After this systems consolidation process, the neocortex can store information for decades.

It is well established that consolidation relies on non-rapid eye movement (NREM) sleep^{10,11,12,13,14,15}. This brain state gives rise to characteristic patterns in the electroencephalogram, including slow waves (∼ 0.5–4 Hz), sleep spindles (∼ 10–16 Hz) and hippocampal ripple oscillations (∼ 80–120 Hz in humans)^16,17,18. During slow wave activity (SWA), neocortical neurons exhibit synchronous membrane potential changes, referred to as UP and DOWN states^19,20,21,22. UP states are periods of increased neural activity, giving rise to depolarization of neurons^23,24. Conversely, DOWN states are silent periods, associated with hyperpolarization^25,26. In the human neocortex, prominent SWA occurs in supragranular layers 2 & 3^21,27. Several studies have demonstrated that precise temporal coupling of spindles and ripples to SWA promotes engram reactivation^{28,29,30,31,32,33,34} and determines success of memory consolidation^{18,35,36,37,38}. Consequently, brain stimulation methods that boost SWA or enhance coupling have a positive effect on memory performance in rodents and humans^{39,40,41,42,43,44}. These observations suggest that SWA and the underlying membrane potential UP and DOWN states initiate mechanisms that augment memory functions. However, in the human brain such mechanisms remain elusive.

One possibility is that UP and DOWN states modulate excitatory synapses in the neocortex to increase synaptic strength during SWA-coupled neural activity. While action potentials (AP) are necessary to initiate transmission in the mammalian neocortex, it has been demonstrated in laboratory animals that presynaptic signals below the AP-threshold (i.e., subthreshold signals) have a modulatory effect on synaptic strength^{45,46,47,48,49,50,51,52,53,54}. For instance, at synapses between neocortical pyramidal neurons in ferrets⁴⁶ and rats⁴⁷ a 1-second-long subthreshold depolarization preceding an AP leads to an increase in synaptic amplitude. Through such mechanisms, UP and DOWN states could tune local synaptic networks to promote long-term synaptic plasticity, which is believed to be fundamental for memory consolidation^2,55.

Objective: Intermittent energy restriction (IER) is an effective weight loss strategy. However, little is known about the dynamic effects of IER on the brain-gut-microbiome axis.

Methods: In this study, a total of 25 obese individuals successfully lost weight after a 2-month IER intervention. FMRI was used to determine the activity of brain regions. Metagenomic sequencing was performed to identify differentially abundant gut microbes and pathways in from fecal samples.

Results: Our results showed that IER longitudinally reduced the activity of obese-related brain regions at different timepoints, including the inferior frontal orbital gyrus in the cognitive control circuit, the putamen in the emotion and learning circuit, and the anterior cingulate cortex in the sensory circuit. IER longitudinally reduced E. coli abundance across multiple timepoints while elevating the abundance of obesity-related Faecalibacterium prausnitzii, Parabacteroides distasonis, and Bacterokles uniformis. Correlation analysis revealed longitudinally correlations between gut bacteria abundance alterations and brain activity changes.

Researchers at Baylor College of Medicine, Jan and Dan Duncan Neurological Research Institute (Duncan NRI) at Texas Children’s Hospital and collaborating institutions have gained new insights into the molecular changes leading to Rett syndrome, a severe neurological disorder caused by mutations in the MeCP2 gene encoding methyl-CpG binding protein 2 (MeCP2).

The team reports in the journal Neuron that loss of MeCP2 in adulthood causes immediate progressive dysregulation of hundreds of genes—some are activated while others are suppressed—and these changes occur well before any measurable deficiencies in neurological function.

The MeCP2 protein is most highly expressed in neurons— brain cells where, like an orchestra conductor, MeCP2 directs the expression of hundreds of genes. When mutations produce a nonfunctional MeCP2 protein, the conductor is no longer present to direct the harmonious expression of genes needed for normal brain function. The resulting discord in gene expression leads to Rett syndrome.

Dr. Ariel Zeleznikow-Johnston hopes to pick up the movement where Jones left off, albeit with the significant twist that his version does not require freezing. A research fellow at Melbourne’s Monash University, Zeleznikow-Johnston wrote the new book, “The Future Loves You: How and Why We Should Abolish Death,” which makes the case that cryopreservation is possible and should be more widely available. Rejecting the popular notion that death endows life with meaning as “palliative philosophy,” Zeleznikow-Johnston’s book instead argues a human’s connectome — a high-resolution map of all their brain connections — could be theoretically recorded perfectly before they die.

Once that happens, that same internal brain activity could be recreated through high-powered computers, while a new brain is grown in a vat via stem cells or some combination of the two. As such, Zeleznikow-Johnston is proposing a spiritual descendant to the cryonics movement (which he dismisses as “unscientific” and “unsubstantiated”), one where the focus is not on preserving tissues but on the “data,” so to speak, of our distinct connectomes.

“We have very strong evidence that the static structure of the neurons is enough to hold onto someone’s memories and personality.”

22q11.2 deletion syndrome (22q) raises schizophrenia risk through skull malformations linked to the Tbx1 gene, affecting cerebellar development. This highlights how non-brain factors like bone defects can influence neurological disorders.

The chromosomal disorder 22q11.2 deletion syndrome (22q) has emerged as one of the strongest risk factors for schizophrenia. Scientists at St. Jude Children’s Research Hospital identified malformed regions of the cerebellum in both laboratory models and patients with 22q, attributing these malformations to improper skull formation.

Additionally, the researchers linked the skull malformation to the loss of a single gene: Tbx1. This research highlights that neurological disorders can arise from sources outside the nervous system, such as defects in skull development. The findings were published in Nature Communications.

Because glucose metabolism is disrupted in several different neurodegenerative disorders, this treatment strategy also shows promise for other brain conditions.

“The beneficial effect on brain metabolism by IDO1 inhibition cuts across different types of pathology,” Andreasson said.

“It is exciting to think that this may be a more general mechanism that could be targeted in other neurodegenerative disorders, like Parkinson’s disease, where you have accumulation of a-synuclein, or ALS, where there is accumulation of tdp-43.”

Summary: SUMO proteins play a key role in activating dormant neural stem cells, vital for brain repair and regeneration. This finding, centered on a process called SUMOylation, reveals how neural stem cells can be “woken up” to aid in brain recovery, offering potential treatments for neurodegenerative diseases.

SUMO proteins regulate neural stem cell reactivation by modifying the Hippo pathway, crucial for cell growth and repair. The study’s insights lay foundational groundwork for developing regenerative therapies to combat conditions like Alzheimer’s and Parkinson’s disease.