The facial nucleus, present in vertebrate animals, is a group of neurons in the brainstem that receives instructions from neurons in the cortex to direct movement of the muscles of the face. For this paper, the authors characterized the facial nucleus of two similar species, African and Asian elephants, with muscular, dexterous trunks. These species’ faces share many similarities, but have distinctly different ear size and trunk morphology—areas controlled by the facial nucleus. The authors used varied methods, matched to the available elephant material, including Nissl staining, cell counting, axonal osmium tetroxide stains, somata drawings, cell fiber counting, and nerve tracing to examine the facial nucleus in specimens from African (n=4) and Asian elephants (n=4 elephants). Stereo Investigator^® software was used to acquire images of thin sections, conduct stereological procedures, and measure cell size and axon diameter.

Two methods were used to quantify cell populations in the elephant facial nucleus, an unbiased stereology approach and a model-based stereology strategy that consisted of complete counts of cell pieces in every tenth section were used. Using unbiased stereology, the researchers counted ~200-300 cells per specimen with the Stereo Investigator optical fractionator probe. To confirm their results, the research team next counted ~5000–8,000 cells and cell fragments per specimen, then corrected for double-counted cells. The results were equivalent; however, the unbiased stereology approach was much less time consuming.

The researchers found that the facial nucleus in elephants is much larger than in most mammals and it is comprised of approximately five-fold more neurons, but at significantly lower neuronal density. African elephants were found to have more neurons in the medial facial subnucleus than Asian elephants, consistent with their much larger and more expressive ears. Dorsal and lateral facial subnuclei, which control movement of the trunk, were elongated compared to other vertebrate mammals and contained many more neurons than land-based species. Interestingly, these regions had a distinct proximal-to-distal cells size increase. Comparison with other species and between newborn and adult elephants suggest that this increase in size is needed for to support the extreme axonal volumes associated with trunk innervation. These cell-size gradients were found to be a unique feature of the elephant facial nucleus. Finally, the research team identified a high-density motor fovea that they believe are associated with the tip of the trunk in African elephants. Asian and African elephants’ trunks differ in that Asian elephants have one dorsal trunk finger and they tend to engage much of their trunk in grasping objects by wrapping them in their trunks, whereas African elephants’ trunks have dorsal and ventral fingers that are often used to pinch objects. Their work suggests that African elephants have more neurons associated with the trunk tip than do Asian elephants and that control of African elephants’ trunk fingers resides in the motor foveae they identified.

The research described here relied heavily on cell-count data that was most efficiently obtained using the optical fractionator probe in Stereo Investigator^®. The authors found strong relationships between the number, density, and size of neurons and the position and function of elephant facial morphology. Their results pose interesting avenues for future research, including the role of ear movement in “auditory and infrasound perception” and follow-up studies on the cell-size differences found in the putative trunk representation in the facial nucleus and how these differences may be involved with elephants’ presumed need to compensate for inherent nerve conduction delays associated with their large size.

Learn more about industry-leading Stereo Investigator^® systems for image acquisition and stereological studies.

View our webinar that introduces Stereo Investigator^® and unbiased stereology.

Reference:

Kaufmann, L. V., Schneeweiß, U., Maier, E., Hildebrandt, T., & Brecht, M. (2022). Elephant Facial Motor Control. Science Advances, 8(43). https://doi.org/10.1126/sciadv.abq2789

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At Dr. Patrick R. Hof’s lab at the Icahn School of Medicine at Mount Sinai, researchers imaged the cerebral cortex using light-sheet fluorescence microscopy and quantified the number of neurons, including those that express proteins involved in Alzheimer’s disease and schizophrenia, using the Image Volume Fractionator¹. This work marks the beginning of an important and ambitious project to build an atlas of cortical cells, using a multi-resolution imaging pipeline. At the pipeline’s highest level of resolution, both the Image Volume Fractionator, for use with thick sections of cleared tissue, and the Optical Fractionator, for much thinner sections, are being used to estimate cell number. The researchers will also use automatic cell detection and plan to compare results obtained using the three methods.

In the paper A Multimodal Imaging and Analysis Pipeline for Creating a Cellular Census of the Human Cerebral Cortex¹, the authors describe the beginning of the effort to build a census of the human cerebral cortex, a laminar structure, that contains layers comprised of different cell types visible using high resolution microscopy. There are a number of different neuronal cell types in each layer, including projection neurons and interneurons, as well as excitatory and inhibitory neurons. Layers can be identified based on different proteins contained in certain cells using fluorescence immunohistochemistry. Calretinin, a calcium-binding protein, is found in a subpopulation of the inhibitory interneurons that contain GABA. Neurofilament protein, which can be found in the cytoskeleton, makes up 30 percent of cortex cells. Parvalbumin, another calcium-binding protein, is also found in a subset of cortical cells.

The cells in the cortex have a purpose that is supported by their neurochemical and anatomical characteristics. Here are two examples involving Alzheimer’s disease and schizophrenia. Calretinin-positive cells in the cortex are spared in Alzheimer’s disease², but neurofilament protein-positive cells degenerate, and that degeneration may predict cognitive decline³. The parvalbumin-containing basket cell is an inhibitory GABAergic interneuron in the cortex that inhibits the main output cell—the pyramidal neuron. Problems with this cell type may affect gamma oscillations, leading to the deficits in cognitive control that accompany schizophrenia⁴.

Wouldn’t it be valuable to have an atlas or census of the cortex that is “zoomable” like a GPS map, and shows the cell types and their connections? Hof. et.al., demonstrate that this is possible using three imaging techniques at increasing resolutions (Fig. 1).

Fig. 1 The three imaging modalities used in this study. Magnetic Resonance Imaging (MRI) is the lowest resolution. Optical Coherence Tomography (OCT) is the mid-resolution. Light Sheet Fluorescence Microscopy (LSFM) is the highest resolution. The Image Volume Fractionator probe is carried out using LSFM. Those images are registered to eliminate distortion to help match them to OCT and the MRI images.

At the most highly resolved level, LSFM, two unbiased stereology techniques are used to build a census inside the atlas: the Optical Fractionator and the new, Image Volume Fractionator. The latter is made possible by tissue clearing methods, which in turn allows for the use of tissue sections that are, in this case, 10 times thicker than for the Optical Fractionator (Fig. 2).

Fig. 2 The Image Volume Fractionator (IVF) was designed to be used on thick sections or large intact specimens. It is much more efficient than working on traditional histological sections that were not cleared and therefore need to be, in this case, 10 times thinner. N is the estimate of number of cells. Systematic random sampling and disector rules are followed while counting.

Since the LSFM images are ten times thicker than the thinner sections needed in the absence of tissue clearing, counting with the Image Volume Fractionator probe can be done more quickly. It is much more efficient to count cells in one large image than in ten separate thinner tissue sections. There is also less sectioning artifact, which helps with registering the higher resolution LSFM images back to the larger volume MRI images.

We are excited to see this new use of the Image Volume Fractionator, which increases efficiency and reduces imaging distortions from physical sectioning. The potential that cleared tissue offers for increasing efficiency is great, but is still largely untapped. As this method is used more frequently, we look forward to hearing feedback from the research community to further improve the capabilities and usability of the Image Volume Fractionator in Stereo Investigator – Cleared Tissue Edition.

References:

1) A Multimodal Imaging and Analysis Pipeline for Creating a Cellular Census of the Human Cerebral Cortex 2021, Constantini, et al., https://www.biorxiv.org/content/10.1101/2021.10.20.464979v1

2) Hof, P. R., Nimchinsky, E. A., Celio, M. R., Bouras, C. & Morrison, J. H. Calretinin, Immunoreactive neocortical interneurons are unaffected in Alzheimer’s disease. 861 Neurosci Lett 152, 145-148 (1993).

3) Bussiere, T. et al. Progressive degeneration of nonphosphorylated neurofilament protei enriched pyramidal neurons predicts cognitive impairment in Alzheimer’s disease: Stereologic analysis of prefrontal cortex area 9. Journal of Comparative Neurology (2003).

4) Glausier, J. R., Fish, K. N. & Lewis, D. A. Altered parvalbumin basket cell inputs in the dorsolateral prefrontal cortex of schizophrenia subjects. Mol Psychiatry 19, 30-36 (2014). Lewis, D. A., Curley, A. A., Glausier, J. R. & Volk, D. W. Cortical parvalbumin interneurons and cognitive dysfunction in schizophrenia. Trends Neurosci 35, 57-67 (2012).

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An immunostained image of myelin basic protein in the cerebella of a mouse brain with an iron-sufficient diet compared with the brain of a mouse exposed to alcohol and fed an iron-insufficient diet. It shows the reduced cerebellar size due to the ID-alcohol combination. Green is MBP immunostain, blue is DAPI for nuclei. Image courtesy of Susan Smith, PhD.

If a pregnant woman drinks alcohol, she risks giving birth to a baby with physical and cognitive deficits – characteristics of fetal alcohol spectrum disorders. In a new study, researchers say that when the mother is low in iron, the consequences are even worse.

The scientists examined two groups of pregnant rats – one group was fed an iron sufficient diet while the other was fed a diet with insufficient iron levels. The offspring from both groups were exposed to alcohol from 4 to 9 days after birth – a time when their brains are going through a growth spurt and are particularly sensitive to alcohol. They were compared to offspring who received an iron-sufficient diet but were not exposed to alcohol. This growth spurt correlates to a growth spurt in humans that occurs during the third trimester of pregnancy.

The researchers used delay and trace eye blink classical conditioning methods to assess the offspring’s learning and memory. Learning impairments were reported in both alcohol-exposed groups regardless of their iron status, but more extreme impairments were seen in iron deficient rats compared to iron sufficient rats. After the behavioral tests were completed, the researchers studied the cerebellum and hippocampus – brain regions involved in learning and memory – at a cellular level.

Using the Optical Fractionator probe in Stereo Investigator, the research team quantified neurons in two different areas of the rat brain: the cerebellar interpositus nucleus and the CA1 region of the hippocampus. Their unbiased stereological analysis revealed significant neuronal loss in the alcohol-exposed iron deficient rat brains compared to the iron sufficient rat brains.

“The most important finding from this study is that maternal iron status strongly influences alcohol’s neurobehavioral damage in the developing offspring,” the authors say in their paper. These data endorse that the treatment of maternal [iron deficiency] through normalization of iron status should improve the child’s developmental outcome despite the gestational alcohol exposure.” (Huebner, et al.)

Huebner, S.M., Tran, T.D., Rufer, E.S., Crump P.M., Smith S.M., (2015) Maternal iron deficiency worsens the associative learning deficits and hippocampal and cerebellar losses in a rat model of fetal alcohol spectrum disorders. Alcoholism: Clinical and Experimental Research doi: 10.1111/acer.12876.

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Phosphorylated tau pS422 immunoreactive profiles (dark brown) in the cortex of P301S mice after repetitive mild TBI. Image courtesy of Dr. Leyan Xu, Department of Pathology, Johns Hopkins University.

Over the course of a football game or a boxing match, athletes may experience a series of mild concussions. Some of these athletes develop a condition known as chronic traumatic encephalopathy (CTE), a neurodegenerative disease characterized by the build-up of abnormal tau protein that eventually leads to dementia. But not every athlete develops CTE after repetitive mild traumatic brain injury, and scientists think genetic factors are involved.

In a recent study, researchers at the Johns Hopkins University School of Medicine found that the density of abnormal tau protein increased exponentially in mice that had a genetic mutation thought to cause neurodegenerative diseases. Their findings contrast with previous studies of mice without genetic mutation, where abnormal tau protein build-up did not occur. This evidence leads the scientists to infer that genetic factors play a role in the onset of CTE.

According to the paper, published in Experimental Neurology, scientists have identified 40 different types of mutations in the gene that makes the brain prone to tau aggregation. “Transgenic mice harboring these mutations can be used to ask whether repetitive mTBI can accelerate onset and course of tauopathy or worsen the outcomes of transgenic disease,” the authors say in their paper.

In this study, Dr. Leyan Xu and his team examined the P301S strain of transgenic mice which harbor a tau gene mutation. After exposing the animals to a series of impact acceleration (IA) injuries involving a weight drop technique, the researchers examined both the neocortex and the retina. The visual tract is a pathway strongly associated with TBI in this mouse model, which is why the researchers investigated the retina in addition to the neocortex.

Using the optical fractionator probe in Stereo Investigator, they analyzed neocortical neurons immunohistochemically labeled with a marker for hyperphosphorylated tau protein – in other words, tau gone awry. They did not witness significant differences in tau build-up between the neocortices of the experimental mice and control mice, however they did see differences between these groups when they examined their retinas. Their findings revealed a 20 fold increase in retinal ganglion cells with hyperphosphorylated tau after one mTBI hit in transgenic mice, compared to controls, a 50 fold increase after four hits, and a 60 fold increase after 12 hits. Both experimental and control mice displayed similar patterns of traumatic axonal injury.

“Our current findings demonstrate that repetitive mTBI accelerates tauopathy in mice predisposed to tau accumulation. A single mTBI event also appears to have an effect in the progression of tauopathy, but repetitive injury has an even greater effect,” (Xu, et al)

Xu, L., Ryu, J., Nguyen, J.V., Arena, J., Rha, E., Vranis, P., Hitt, D., Marsh-Armstrong, N., Koliatsos, V.E., (2015) Evidence for accelerated tauopathy in the retina of transgenic P301S tau mice exposed to repetitive mild traumatic brain injury. Experimental Neurology. doi: 10.1016/j.expneurol.2015.08.014

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Neuroscientists at Ludwig-Maximillians-University of Munich have made new revelations about the development of cerebellar granule neurons. The smallest and most numerous type of neuron in the human brain, these cells transmit motor and sensory information to Purkinje cells, large neurons that are said to play a role in coordinating motor movement and are the sole source of output for the cerebellar cortex.

Human cerebellum section with silver staining. Image from the Iowa Virtual Slidebox

The scientists found that humans generate most cerebellar granule cells after birth (85 percent), a finding that contradicts previous studies, which say the majority of these cells are generated prenatally.

Using Stereo Investigator, the researchers conducted a stereological study of the cerebella of 14 infants who died before their first birthday. They used Optical Fractionator probe to estimate the number of Purkinje and granule cells in cresyl violet stained sections of each brain. Performing a statistical analysis with the information they acquired, they determined that the number of granule cells per Purkinje cell in the human cerebellum increases with age during the first year of life. According to the paper, the population of granule cells grows from approximately 485 per Purkinje cell in the first month after birth to approximately 2,700 at month 11.

“The results of the present study indicate that damaging events during the first year of life may affect the cerebellum and, therefore, motor control, attention, emotions, mood and social behaviors much more severely than generally thought,” the authors say in their paper, adding that more new research should be carried out on postnatal neurogenesis in the human brain.

Kiessling, M., Büttner, A., Butti, C., Müller-Starck, J., Milz, S., Hof, P., Frank, H., Schmitz, C. (2013). Cerebellar granule cells are generated postnatally in humans. Brain Structure and Function, 1-16. doi: 10.1007/s00429-013-0565-z.

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The granule cell layer of the dentate gyrus. Image provided by Mark Maynard.

Binge drinking damages brain regions responsible for memory, decision-making, and behavioral control. After a binge, the brain begins to heal itself but not much is known about this self-repair process. In a study published in PLoS ONE, researchers used rats to find that binge drinking damages the hippocampus, and exercise reverses this damage.

The study found that excessive ethanol killed granule neurons in the dentate gyrus (DG), a part of the hippocampus, and significantly decreased the volume of the DG. Rats that exercised after binging had more DG granule neurons and a larger DG than rats that did not exercise after a binge. In fact, rats that exercised after binging had a similar number of DG neurons and a similar DG volume to that of controls, indicating that exercise almost fully reversed damaged to the DG caused by binge drinking.

“The granule cell layer of the dentate gyrus is an incredibly dense layer of mature neurons that is typically very difficult to quantify and make assessments of,” said Mark E. Maynard, a co-author of the paper. “In addition, the hippocampus itself is a very large structure relative to the rest of the rodent brain, adding to the difficulty of quantifying changes to it.”

To analyze the dentate gyrus, Mark Maynard and Dr. Leasure used an MBF system equipped with a Nikon Eclipse 80i microscope and Stereo Investigator. They used the Optical Fractionator probe in Stereo Investigator to quantify the number of granule cells in the DG and the Cavalieri probe to quantify volume of the DG.

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“Using Stereo Investigator software we were able to look at a sample of the dentate gyrus and get an accurate estimate of the number of remaining granule cells and volume of the layer itself that was sensitive, to detect changes in response to binge alcohol exposure,” said Mark Maynard.

Mark Maynard and Dr. Leasure describe the stereology study in detail in the methods section of their paper. Read it here: Maynard ME, Leasure JL (2013) Exercise Enhances Hippocampal Recovery following Binge Ethanol Exposure. PLoS ONE 8(9): e76644. doi:10.1371/ journal.pone.0076644

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Patients with Huntington’s disease deteriorate physically, cognitively, and emotionally. There is no cure for the inherited illness, but scientists may have found a way to slow down the onset of symptoms. Researchers in Quebec increased the expression of a molecule known as pre-enkephalin (pENK) in a mouse model of Huntington’s disease (HD) and saw promising results.

Since reduced expression of pENK is a hallmark of the disease, and neurons containing this molecule are some of the first cells to die in the brains of HD patients, the researchers hypothesized that an HD brain over-expressing pENK might have beneficial results. Their study offers the first evidence that increased pENK expression leads to a delay in muscle dysfunction, improved motor activity, memory, and lower anxiety in early-onset HD.

To upregulate pENK, the researchers injected a viral vector carrying the molecule into the striatum of five-week old mice. Behavior tests conducted before and after the injection measured benchmarks of degeneration in the mouse model, including grip strength, clasping, open field movement, anxiety, memory and learning, and novel object recognition. At ten-weeks-old, HD mice over-expressing pENK performed better on many tests compared with controls (HD mice that did not receive pENK treatment). In other words, symptoms like motor dysfunction, which were assessed with the “grip strength” and “clasping” tests, appeared at six-weeks in the untreated HD mice, but didn’t show up until eight or ten weeks in mice over-expressing pENK.

Striatal neurons also benefited from pENK overexpression. Using the Optical Fractionator probe with Stereo Investigator to perform a stereological study of the region, the researchers saw more striatal neurons in 10-week-old pENK-treated HD mice compared to controls.

“The results of this study might open new horizon to investigate the cellular and molecular mechanisms by which enkephalin modulates motor response and signaling in HD, and may also contribute to the development of new therapeutical strategies and the gain in the quality of life in HD patients,” the authors say in their paper.

Bissonnette, S., Vaillancourt, M., Hébert, S. S., Drolet, G., & Samadi, P. (2013). Striatal Pre-Enkephalin Overexpression Improves Huntington’s Disease Symptoms in the R6/2 Mouse Model of Huntington’s Disease. Plos one, 8(9), e75099. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3770591/

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“Treatment options are clearly urgently required to prevent the brain damage and associated memory deficits that follow extremely premature birth,” say the authors of a study published last month in the Journal of Neuroscience.

Treatment options are limited, the authors say, because current small animal models fall short in their mimicry of the extremely premature human brain. However, the researchers from the University of Otago in New Zealand have come up with a new animal model for human extreme prematurity, which they say more closely resembles the pathological and behavioral deficits seen among this populationThe research team developed the model by exposing rats to an oxygen deficient environment at one to three days of age, a period equivalent to 24-26 weeks human gestation.

By performing behavioral assessments and a stereological analysis of several different regions of the rat brains, the scientists saw similarities in “short and long-term white matter neuropathological injury, gray matter volume loss, and long-term memory deficits” between the rats and children born extremely prematurely.

Oligodendrocytes, pictured here with a green fluorescent protein, form a myelin sheath – the insulation around axons. The extremely premature brain features a lower number of pre-oligodendrocytes, thereby decreasing myelination, a characteristic which has been associated with ADHD. Image courtesy of Wikimedia Commons.

They used the Cavalieri, optical fractionator, optical disector, and nucleator probes in Stereo Investigator to quantify different elements of brain tissue. The researchers found that, compared to controls, the hypoxic rats had a lower number of pre-oligodendrocytes at four-days-old, and at 14-days-old displayed less cerebral white matter volume and myelin, as well as less cerebral cortical and striatal gray matter volume without neuronal loss – pathological characteristics also present in the brains of humans born extremely premature.

Behavioral tests showed the mice mimicked behavioral characteristics in children and adults born extremely prematurely, displaying memory deficits and ADHD-like hyperactivity.

“This new rat model provides a clinically relevant tool to investigate numerous cellular, molecular, and therapeutic questions on brain injury attributable to extreme prematurity,” the authors say.

Oorschot, Dorothy E., Voss, Logan, Covey, Matthew V., Goddard, Liping, Huang, William, Birchall, Penny, Bilkey, David K. and Kohe, Sarah E. (2013). Spectrum of Short- and Long-Term Brain Pathology and Long-Term Behavioral Deficits in Male Repeated Hypoxic Rats Closely Resembling Human Extreme Prematurity. The Journal of Neuroscience, 33(29), 11863–11877. doi: 10.1523/jneurosci.0342-12.2013.

Image courtesy: Wikimedia Commons

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If one area isn’t working, another part can step in. Plasticity is one of the brain’s most beautiful attributes. Recent research has documented the organ’s ability to compensate in the face of damage, and now a new study identifies a key region for compensation when the damage occurs in the hippocampus.

The region is the medial prefrontal cortex (mPFC). It’s an integral part of the hippocampal-prefrontal-amygdala circuit involved with memory formation – specifically with contextual fear memories. In their study, published last month in Proceedings of the National Academy of Sciences, researchers at the University of California, Los Angeles identify a microcircuit in the mPFC that can encode memories when the dorsal hippocampus is damaged.

By conducting an unbiased stereological count of active neurons in the mPFC of brain damaged rats with Stereo Investigator‘s Optical Fractionator probe, the researchers determined that two subregions are essential for compensation: the prelimbic (PL) and infralimbic (IL) subregions which communicate with each other and balance sensory input to help the brain form memories.

“The neural signature of this compensation,” the scientists say in their paper, “is a silencing of basolateral amygdala-projecting IL neurons complemented by an increase in the activation of PL neurons projecting to the basolateral amygdala.”

During the course of the study, the researchers examined the behavior and brains of rats which had undergone several sessions of fear conditioning through a variety of behavioral tests. Prior to fear conditioning, the rats received lesions to either their hippocampus alone, their hippocampus and IL cortex, or their hippocampus and PL cortex.

Since the prefrontal cortex does not lie adjacent to the hippocampus, the study shows that the compensatory region does not have to be directly proximal to the site of injury – a common belief among the scientific community, according to the paper. The research also sheds new light on the plasticity of the fear system circuit.

“[Our results] open up the doors to the development of targeted approaches for the treatment of memory loss–related disorders due to brain damage, disease, or aging,” the authors conclude.

Zelikowsky, M., Bissiere, S., Hast, T. A., Bennett, R. Z., Abdipranoto, A., Vissel, B., & Fanselow, M. S. (2013). Prefrontal microcircuit underlies contextual learning after hippocampal loss. Proceedings of the National Academy of Sciences. doi: 10.1073/pnas.1301691110

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Obstetricians and midwifes have long hailed the benefits of folic acid during pregnancy. Now new research offers evidence that choline is another important nutrient for the developing fetus. Found in foods like eggs and cauliflower, choline is known to aid healthy liver function. But in the past few years, studies have shown that the nutrient also plays a role in brain development. One recent study by Velasquez and colleagues claims that increased choline during pregnancy may offer a possible therapy for Down syndrome.

The study describes improvements in spatial cognition and increases in neurogenesis in an adult mouse model of Down syndrome – a disorder characterized by decreased intellectual capacity and early onset of dementia.

To test whether or not choline supplementation would have an impact on learning and memory in adulthood, the research group raised a population of mice, half of which were models of Down syndrome (Ts65Dn mice). Half of the Down syndrome mice and half of the normal mice were birthed by mothers which were given four and a half times more choline than the other mothers in their diets during pregnancy and lactation, while the mothers of the other half of each group ate foods with standard levels of the nutrient.

Using Stereo Investigator to conduct an unbiased stereological study, the researchers observed a higher level of new cells in the supplemented Down syndrome adult mice. The scientists used the optical fractionator method to quantify cells labeled with doublecortin (DCX), a marker for immature neurons, in the hippocampus, a brain region associated with learning and memory. These mice also performed better than non-supplemented Down syndrome mice in a radial arm water maze, leading the scientists to speculate on the existence of a link between increased neurogenesis and enhanced spatial learning.

“The present study demonstrated that supplementing the maternal diet with additional choline during pregnancy and lactation improves spatial cognition and hippocampal neurogenesis in adult Ts65Dn offspring. If these findings generalize to humans, [maternal choline supplementation] could provide a therapy to normalize brain development and cognitive function in [Down syndrome] as well as possibly slow the neurodegeneration associated with both Down syndrome and Alzheimer’s disease,” the authors say in their paper.

Velazquez, R., Ash, J. A., Powers, B. E., Kelley, C. M., Strawderman, M., Luscher, Z. I., Ginsberg, S., Mufson, E., Strupp, B. J. (2013). Maternal choline supplementation improves spatial learning and adult hippocampal neurogenesis in the Ts65Dn mouse model of Down syndrome. Neurobiology of Disease. doi: 10.1016/j.nbd.2013.04.016

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