New neurons continue to form in the adult human hippocampus

Amazing stuff!

"A study ... presents compelling new evidence that neurons in the brain's memory center, the hippocampus, continue to form well into late adulthood. ..."

"... To localise these cells, the researchers used two techniques that show where in the tissue different genes are active: RNAscope and Xenium. These methods confirmed that the newly formed cells were located in a specific area of the hippocampus called the dentate gyrus. This area is important for memory formation, learning and cognitive flexibility. ...

... The results show that the progenitors of adult neurons are similar to those of mice, pigs and monkeys, but that there are some differences in which genes are active. There were also large variations between individuals – some adult humans had many neural progenitor cells, others hardly any at all. ..."

From the perspective's abstract:

"Challenging the long-held dogma that the generation of neurons ends in mammals early after birth, pioneering papers in the 1960s suggested that new neurons are born in the rodent brain throughout life.

These adult-born neurons were detected in several regions, including the hippocampus, which is important for learning, memory, and mood control and is impaired in diseases such as Alzheimer’s disease.

From this emerged a decades-long controversy, with numerous studies providing evidence for—or against—the lifelong activity of neural progenitor cells (NPCs) as a source of newborn neurons in the human hippocampus.

On page 58 of this issue, Dumitru et al. (1) report the use of single-nucleus RNA sequencing (snRNA-seq) and spatial transcriptomics to identify cells with transcriptional signatures of NPCs and newborn neurons in the human hippocampus from childhood to old age. Together with previous work (2–4), the findings indicate that neurogenesis persists throughout life in the human hippocampus."

From the editor's summary and abstract:

"Editor’s summary

Whether adult neurogenesis occurs in the human hippocampus is one of the most debated issues in neuroscience. Dumitru et al. used a single-cell transcriptomic approach to address this issue in human samples of various ages from birth through adulthood (see the Perspective by Quiniou and Jessberger). Machine learning algorithms helped the authors to identify proliferating neural progenitor cells in the adolescent and adult human hippocampus that resembled progenitor cells found in mouse and pig. The results support the idea that adult neurogenesis occurs in the human hippocampus and add valuable insights of scientific and medical interest. ...

Abstract

Continuous adult hippocampal neurogenesis is involved in memory formation and mood regulation but is challenging to study in humans. Difficulties finding proliferating progenitor cells called into question whether and how new neurons may be generated.

We analyzed the human hippocampus from birth through adulthood by single-nucleus RNA sequencing. We identified all neural progenitor cell stages in early childhood.

In adults, using antibodies against the proliferation marker Ki67 and machine learning algorithms, we found proliferating neural progenitor cells. Furthermore, transcriptomic data showed that neural progenitors were localized within the dentate gyrus. The results contribute to understanding neurogenesis in adult humans."

New neurons continue to form in the adult human hippocampus: Study

New research confirms that neurons form in the adult brain (original news release) "A study in the journal Science presents compelling new evidence that neurons in the brain’s memory centre, the hippocampus, continue to form well into late adulthood. The research from Karolinska Institutet provides answers to a fundamental and long-debated question about the human brain’s adaptability."

Sequenced evidence (no public access) "Transcriptome analyses identify neural progenitor cells in the adult human hippocampus"

Identification of proliferating neural progenitors in the adult human hippocampus (no public access)

Do we make new neurons in adult brains?

Recommendable! When old, obsolete scientific dogmas die hard!

I feel already much better as an old dude! 😊

"... Now, an AI-powered study may finally have settled the debate by identifying neural progenitor cells in adult hippocamp[us].

More than a century ago, Santiago Ramon y Cajal—the “father of neuroscience”—declared that nerve cells are “fixed, ended, and immutable” after development. Ever since, scientists have generally assumed that he was correct and that neurogenesis stopped abruptly after childhood. ...

In the 1990s and 2000s, even more research challenged this assumption, finding what appeared to be actively dividing cells—known as neural progenitors—in the adult human brain. Still, some neuroscientists remained unpersuaded. ..."

"Challenging the long-held dogma that the generation of neurons ends in mammals early after birth, pioneering papers in the 1960s suggested that new neurons are born in the rodent brain throughout life.

These adult-born neurons were detected in several regions, including the hippocampus, which is important for learning, memory, and mood control and is impaired in diseases such as Alzheimer’s disease.

From this emerged a decades-long controversy, with numerous studies providing evidence for—or against—the lifelong activity of neural progenitor cells (NPCs) as a source of newborn neurons in the human hippocampus. ... Dumitru et al. (1) report the use of single-nucleus RNA sequencing (snRNA-seq) and spatial transcriptomics to identify cells with transcriptional signatures of NPCs and newborn neurons in the human hippocampus from childhood to old age. Together with previous work (2–4), the findings indicate that neurogenesis persists throughout life in the human hippocampus."

From the editor's note and the abstract:

"Editor’s summary

Whether adult neurogenesis occurs in the human hippocampus is one of the most debated issues in neuroscience. Dumitru et al. used a single-cell transcriptomic approach to address this issue in human samples of various ages from birth through adulthood ... Machine learning algorithms helped the authors to identify proliferating neural progenitor cells in the adolescent and adult human hippocampus that resembled progenitor cells found in mouse and pig. The results support the idea that adult neurogenesis occurs in the human hippocampus and add valuable insights of scientific and medical interest. ...

Abstract

Continuous adult hippocampal neurogenesis is involved in memory formation and mood regulation but is challenging to study in humans. Difficulties finding proliferating progenitor cells called into question whether and how new neurons may be generated. We analyzed the human hippocampus from birth through adulthood by single-nucleus RNA sequencing.

We identified all neural progenitor cell stages in early childhood.

In adults, using antibodies against the proliferation marker Ki67 and machine learning algorithms, we found proliferating neural progenitor cells.

Furthermore, transcriptomic data showed that neural progenitors were localized within the dentate gyrus. The results contribute to understanding neurogenesis in adult humans."

ScienceAdviser

Sequenced evidence "Transcriptome analyses identify neural progenitor cells in the adult human hippocampus"

Identification of proliferating neural progenitors in the adult human hippocampus (no public access)

Clear chemical connection between physical activity and brain health

Amazing stuff! Use it or loose it!

"... Now, scientists have shown in cell studies that the connection may be more direct, which opens the door to more targeted physical therapies for brain health and potential treatment of neurodegenerative conditions. ...
The scientists ... were able to demonstrate through mice muscle cells how their contraction caused hippocampal neurons to fire off larger and more frequent electrical signals. Within days, these stronger and healthier signals became more synchronized, mimicking neural organization in the brain. ..."

"... To isolate the chemicals released by contracting muscles and test them on hippocampal neurons, the researchers collected small muscle cell samples from mice and grew them in cell culture dishes in the lab. When the muscle cells matured, they began to contract on their own, releasing their chemical signals into the cell culture.

The research team added the culture, which now contained the chemical signals from the mature muscle cells, to another culture containing hippocampal neurons and other support cells known as astrocytes. Using several measures, including immunofluorescent and calcium imaging to track cell growth and multi-electrode arrays to record neuronal electrical activity, they examined how exposure to these chemical signals affected the hippocampal cells.

The results were striking. Exposure to the chemical signals from contracting muscle cells caused hippocampal neurons to generate larger and more frequent electrical signals — a sign of robust growth and health. Within a few days, the neurons started firing these electrical signals more synchronously, suggesting that the neurons were forming a more mature network together and mimicking the organization of neurons in the brain. ...
“Ultimately, our research may contribute to the development of more effective exercise regimens for cognitive disorders such as Alzheimer's disease,” ..."

From the highlights and abstract:

"Highlights

• Contracting muscle media enhances hippocampal neuronal activity.

• Contracting muscle media expedites synaptic maturation.

• Contracting muscle media accelerates accumulation of filamentous actin at synapses.

• Contracting muscle media induces significant astrocyte and neuron proliferation.

• Astrocytes release factors that inhibit muscle media-induced neuronal activity.

Abstract

Exercise supports brain health in part by enhancing hippocampal function. The leading hypothesis is that muscles release factors when they contract (e.g., lactate, myokines, growth factors) that enter circulation and reach the brain where they enhance plasticity (e.g., increase neurogenesis and synaptogenesis). However, it remains unknown how the muscle signals are transduced by the hippocampal cells to modulate network activity and synaptic development. Thus, we established an in vitro model in which the media from contracting primary muscle cells (CM) is applied to developing primary hippocampal cell cultures on a microelectrode array. We found that the hippocampal neuronal network matures more rapidly (as indicated by synapse development and synchronous neuronal activity) when exposed to CM than regular media (RM). This was accompanied by a 4.4- and 1.4-fold increase in the proliferation of astrocytes and neurons, respectively. Further, experiments established that factors released by astrocytes inhibit neuronal hyper-excitability induced by muscle media, and facilitate network development. Results provide new insight into how exercise may support hippocampal function by regulating astrocyte proliferation and subsequent taming of neuronal activity into an integrated network."

Clear chemical connection between physical activity and brain health

Exercise releases chemical signals that boost brain health Beckman researchers studied how chemical signals from contracting muscles promote healthy brains. Their findings reveal how these signals help grow and regulate new brain networks while also pointing toward ways of improving brain health through exercise.

Astrocyte-mediated Transduction of Muscle Fiber Contractions Synchronizes Hippocampal Neuronal Network Development (no public access)

Hippocampal neurons (yellow) surrounded by astrocytes (green) in a cell culture from the study.

Did this gene give modern human brains their edge?

Amazing stuff!

"More than 500,000 years ago, the ancestors of Neanderthals and modern humans were migrating around the world when a fateful genetic mutation caused some of their brains to suddenly improve. This mutation ... dramatically increased the number of brain cells in the hominins that preceded modern humans, probably giving them a cognitive advantage over their Neanderthal cousins. ..."

"... Pinson et al. report that expression of a variant of human transketolase-like protein 1 (TKTL1) increases the number of bRGs in modern humans and thereby the output of upper layer projection neurons. This genetic change could contribute to differences in cognition with extinct archaic humans."

From the abstract:

"Neanderthal brains were similar in size to those of modern humans. We sought to investigate potential differences in neurogenesis during neocortex development. Modern human transketolase-like 1 (TKTL1) differs from Neanderthal TKTL1 by a lysine-to-arginine amino acid substitution. Using overexpression in developing mouse and ferret neocortex, knockout in fetal human neocortical tissue, and genome-edited cerebral organoids, we found that the modern human variant, hTKTL1, but not the Neanderthal variant, increases the abundance of basal radial glia (bRG) but not that of intermediate progenitors (bIPs). bRG generate more neocortical neurons than bIPs. The hTKTL1 effect requires the pentose phosphate pathway and fatty acid synthesis. Inhibition of these metabolic pathways reduces bRG abundance in fetal human neocortical tissue. Our data suggest that neocortical neurogenesis in modern humans differs from that in Neanderthals."

Did this gene give modern human brains their edge? A mutation present in modern humans seems to drive greater neuron growth than does an ancient hominin version.

Human TKTL1 implies greater neurogenesis in frontal neocortex of modern humans than Neanderthals (no public access)

Scaling brain neurogenesis across evolution (no public access) A genetic change could explain increased cortical neurogenesis in modern humans

Scientists Discover "Gorditas" and Other Novel Brain Cell Types

Amazing stuff! One would wish billionaires like Jeff Bezos, Richard Branson, and Elon Musk would invest more money in brain research instead of space race trips! There is still so much to discover regarding our brains!

"... The results suggest new roles for glial cells, best known for providing support to neurons, and could prompt a better understanding of how brains remain plastic into adulthood, when the vast majority of neurons no longer undergo cell division.... Most mammalian brain cells, be they neurons or glia, are generated during embryonic development, and reservoirs of stem cells become largely, if not entirely, dormant in adulthood. The small trickle of activity that is left can help the brain respond to change, sometimes by generating new neurons to help with learning or by producing cells in response to injury or disease.
One pool exists in the brains of adult humans and mice, in an area called the ventricular-subventricular zone (V-SVZ). The walls of the two lateral ventricles, cavities filled with cerebrospinal fluid, are lined with stem cells, and along these walls, the cells have a regional identity—where a stem cell lies on the wall dictates what it differentiates into ..."

"Quiescent [dormant] neural stem cells (NSCs) in the adult mouse ventricular-subventricular zone (V-SVZ) undergo activation to generate neurons and some glia. Here we show that platelet-derived growth factor receptor beta (PDGFRβ) is expressed by adult V-SVZ NSCs that generate olfactory bulb interneurons and glia. Selective deletion of PDGFRβ in adult V-SVZ NSCs leads to their release from quiescence, uncovering gliogenic domains for different glial cell types. These domains are also recruited upon injury. We identify an intraventricular oligodendrocyte progenitor derived from NSCs inside the brain ventricles that contacts supraependymal axons."

Scientists Discover "Gorditas" and Other Novel Brain Cell Types | The Scientist Magazine® A pool of neural stem cells that ordinarily lies dormant in the brains of adult mice spawns two types of never-before-documented glial cells when artificially reactivated, potentially pointing to a novel mechanism of brain plasticity.

Release of stem cells from quiescence reveals gliogenic domains in the adult mouse brain (no public access)