Older news items (pre-2010) brought over from the old website
‘Memory gene’ impacts driving performance
People with a particular variant (“met”) of the COMT gene performed more than 20% worse on a driving test than people without it. About 30% of Americans have the variant, which limits the availability of the vital protein BDNF during activity. Previous studies have shown that in people with the variant, episodic (event) memory is poorer, and a smaller portion of the brain is stimulated when doing a task. The study involved 29 people, of whom 7 had the gene variant, driving 15 laps on a simulator that required them to learn the nuances of a track programmed to have difficult curves and turns. The test was repeated 4 days later. Those with the variant did worse on both tests than the other participants, and they remembered less the second time. However, the gene isn’t all bad — although carriers don't recover as well after a stroke, they retain their mental sharpness longer in the case of neurodegenerative disease.
[1283] McHughen, S. A., Rodriguez P. F., Kleim J. A., Kleim E. D., Crespo L M., Procaccio V., et al.
(2010). BDNF Val66Met Polymorphism Influences Motor System Function in the Human Brain.
Cereb. Cortex. 20(5), 1254 - 1262.
http://www.sciencedaily.com/releases/2009/10/091028134637.htm
http://www.miller-mccune.com/news/are-you-a-bad-driver-it-may-not-be-your-fault-1577
http://www.eurekalert.org/pub_releases/2009-10/uoc--bdm102809.php
Two studies help explain the spacing effect
I talked about the spacing effect in my last newsletter. Now it seems we can point to the neurology that produces it. Not only that, but the study has found a way of modifying it, to improve learning. It’s a protein called SHP-2 phosphatase that controls the spacing effect by determining how long resting intervals between learning sessions need to last so that long-lasting memories can form. The discovery happened because more than 50% of those with a learning disorder called Noonan's disease have mutations in a gene called PTP11, which encodes the SHP-2 phosphatase protein. These mutations boost the activity levels of SHP-2 phosphatase, which, in genetically modified fruit flies, disturbs the spacing effect by increasing the interval before a new chemical signal can occur (it is the repeated formation and decay of these signals that produces memory). Accordingly, those with the mutation need longer periods between repetitions to establish long-term memory.
[1433] Pagani, M. R., Oishi K., Gelb B. D., & Zhong Y.
(2009). The Phosphatase SHP2 Regulates the Spacing Effect for Long-Term Memory Induction.
Cell. 139(1), 186 - 198.
http://www.eurekalert.org/pub_releases/2009-10/cshl-csi092809.php
A study involving Aplysia (often used as a model for learning because of its simplicity and the large size of its neural connections) reveals that spaced and massed training lead to different types of memory formation. The changes at the synapses that underlie learning are controlled by the release of the neurotransmitter serotonin. Four to five spaced applications of serotonin generated long-term changes in the strength of the synapse and less activation of the enzyme Protein kinase C Apl II, leading to stronger connections between neurons. However, when the application of serotonin was continuous (as in massed learning), there was much more activation of PKC Apl II, suggesting that activation of this enzyme may block the mechanisms for generating long-term memory, while retaining mechanisms for short-term memory.
[1504] Villareal, G., Li Q., Cai D., Fink A. E., Lim T., Bougie J. K., et al.
(2009). Role of Protein Kinase C in the Induction and Maintenance of Serotonin-Dependent Enhancement of the Glutamate Response in Isolated Siphon Motor Neurons of Aplysia californica.
J. Neurosci.. 29(16), 5100 - 5107.
http://www.eurekalert.org/pub_releases/2009-10/mu-wow100109.php
Smart gene helps brain cells communicate
For the second time, scientists have created a smarter rat by making their brains over-express CaMKII, a protein that acts as a promoter and signaling molecule for the NR2B subunit of the NMDA receptor. Over-expressing the gene lets brain cells communicate a fraction of a second longer. The research indicates that it plays a crucial role in initiating long-term potentiation. The NR2B subunit is more common in juvenile brains; after puberty the NR2A becomes more common. This is one reason why young people tend to learn and remember better — because the NR2B keeps communication between brain cells open maybe just a hundred milliseconds longer than the NR2A. Although this genetic modification is not something that could probably be replicated in humans, it does validate NR2B as a drug target for improving memory in healthy individuals as well as those struggling with Alzheimer's or mild dementia.
[599] Wang, D., Cui Z., Zeng Q., Kuang H., Wang P. L., Tsien J. Z., et al.
(2009). Genetic Enhancement of Memory and Long-Term Potentiation but Not CA1 Long-Term Depression in NR2B Transgenic Rats.
PLoS ONE. 4(10), e7486 - e7486.
Full text at http://dx.plos.org/10.1371/journal.pone.0007486
http://www.eurekalert.org/pub_releases/2009-10/mcog-sr101909.php
Common variation in gene linked to structural changes in the brain
Variations in the regions of the gene MECP2, previously associated with Retts Syndrome, autism, and mental retardation, has been found to be associated with changes in brain structure in both healthy individuals and patients with neurological and psychiatric disorders. The study used data from 289 healthy and psychotic subjects (the TOP study), and 655 healthy and demented patients (mostly Alzheimer's; from the ADNI study). The most significant genetic variation resulted in reduced surface area in the cortex (in particular in the cuneus, fusiform gyrus, pars triangularis), and was specific to males.
[297] Schork, N. J., Andreassen O. A., Dale A. M., Joyner A. H., Roddey J. Cooper, Bloss C. S., et al.
(2009). A common MECP2 haplotype associates with reduced cortical surface area in humans in two independent populations.
Proceedings of the National Academy of Sciences. 106(36), 15483 - 15488.
http://www.eurekalert.org/pub_releases/2009-08/uoc--cvi081709.php
http://www.eurekalert.org/pub_releases/2009-08/sri-sru081809.php
Genes more important for IQ as children get older
Data from six studies carried out in the US, the UK, Australia and the Netherlands, involving a total of 11,000 pairs of twins, has revealed that genes become more important for intelligence as we get older. The researchers calculated that genes accounted for some 41% of the variation in intelligence in 9 year olds, rising to 55% in 12 year olds, and 66% in 17 year olds. It was suggested that as they get older, children get better at controlling (or perhaps are allowed to have more control over) their environment, which they do in a way that accentuates their ‘natural’ abilities — bright children feed their abilities; less bright children choose activities and friends that are less challenging.
Haworth, C.M.A. et al. 2009. R Plomin The heritability of general cognitive ability increases linearly from childhood to young adulthood. Molecular Psychiatry, advance online publication 2 June 2009; doi: 10.1038/mp.2009.55
http://www.newscientist.com/article/mg20327174.600-genes-drive-iq-more-as-kids-get-older.html
Early maternal experience can affect memory in her offspring
A study of pre-adolescent mice with a genetically-created defect in memory has found that a mere two weeks exposure to a stimulating environment resulted in a reversal of the memory defect. But most surprisingly, it was also found that this effect was passed on to the next generation, even though they had the same genetic defect and even though they had no such experience themselves, and even when they were reared by other mice (not their mothers). It’s worth emphasizing that the enrichment occurs for the mother long before she’s fertile, yet still benefits her offspring. The finding adds to many recent studies showing that genes are more malleable than we thought.
[1434] Arai, J. A., Li S., Hartley D. M., & Feig L. A.
(2009). Transgenerational Rescue of a Genetic Defect in Long-Term Potentiation and Memory Formation by Juvenile Enrichment.
J. Neurosci.. 29(5), 1496 - 1502.
http://www.physorg.com/news152905156.html
http://www.eurekalert.org/pub_releases/2009-02/rumc-wym020209.php
http://www.eurekalert.org/pub_releases/2009-02/tuhs-dyk012909.php
A gene that influences intelligence
A study involving more than 2000 people from 200 families has found a link between the gene CHRM2, that activates multiple signaling pathways in the brain involved in learning, memory and other higher brain functions, and performance IQ. Researchers found that several variations within the CHRM2 gene (which is on chromosome 7) could be correlated with slight differences in performance IQ scores, which measure a person's visual-motor coordination, logical and sequential reasoning, spatial perception and abstract problem solving skills, and when people had more than one positive variation in the gene, the improvements in performance IQ were cumulative. Intelligence is a complex attribute that results from a combination of many genetic and environmental factors, so don’t interpret this finding to mean we’ve found a gene for intelligence.
[1173] Edenberg, H., Porjesz B., Begleiter H., Hesselbrock V., Goate A., Bierut L., et al.
(2007). Association of CHRM2 with IQ: Converging Evidence for a Gene Influencing Intelligence.
Behavior Genetics. 37(2), 265 - 272.
http://www.eurekalert.org/pub_releases/2007-02/wuso-gag022607.php
Common gene version optimizes thinking but carries a risk
On the same subject, another study has found that the most common version of DARPP-32, a gene that shapes and controls a circuit between the striatum and prefrontal cortex, optimizes information filtering by the prefrontal cortex, thus improving working memory capacity and executive control (and thus, intelligence). However, the same version was also more prevalent among people who developed schizophrenia, suggesting that a beneficial gene variant may translate into a disadvantage if the prefrontal cortex is impaired. In other words, one of the things that make humans more intelligent as a species may also make us more vulnerable to schizophrenia.
[864] Kolachana, B., Kleinman J. E., Weinberger D. R., Meyer-Lindenberg A., Straub R. E., Lipska B. K., et al.
(2007). Genetic evidence implicating DARPP-32 in human frontostriatal structure, function, and cognition.
Journal of Clinical Investigation. 117(3), 672 - 682.
http://www.sciencedaily.com/releases/2007/02/070208230059.htm
http://www.eurekalert.org/pub_releases/2007-02/niom-cgv020707.php
Genetic cause for word-finding disease
Primary Progressive Aphasia is a little-known form of dementia in which people lose the ability to express themselves and understand speech. People can begin to show symptoms of PPA as early as in their 40's and 50's. A new study has found has discovered a gene mutation in two unrelated families in which nearly all the siblings suffered from PPA. The mutations were not observed in the healthy siblings or in more than 200 controls.
[1164] Hutton, M. L., Graff-Radford N. R., Mesulam M. Marsel, Johnson N., Krefft T. A., Gass J. M., et al.
(2007). Progranulin Mutations in Primary Progressive Aphasia: The PPA1 and PPA3 Families.
Arch Neurol. 64(1), 43 - 47.
http://www.eurekalert.org/pub_releases/2007-01/nu-rdg011507.php
Longevity gene also helps retain cognitive function
The Longevity Genes Project has studied 158 people of Ashkenazi, or Eastern European Jewish, descent who were 95 years of age or older. Those who passed a common test of mental function were two to three times more likely to have a common variant of a gene associated with longevity (the CETP gene) than those who did not. When the researchers studied another 124 Ashkenazi Jews between 75 and 85 years of age, those subjects who passed the test of mental function were five times more likely to have this gene variant than their counterparts. The gene variant makes cholesterol particles in the blood larger than normal.
[916] Barzilai, N., Atzmon G., Derby C. A., Bauman J. M., & Lipton R. B.
(2006). A genotype of exceptional longevity is associated with preservation of cognitive function.
Neurology. 67(12), 2170 - 2175.
http://tinyurl.com/yrf5s4
http://www.eurekalert.org/pub_releases/2006-12/aaon-lga121906.php
'Memory gene' identified
Analysis of the human genome has revealed a gene associated with memory performance. The gene is called Kibra, and is expressed in the hippocampus. According to brain scans, people with the version of the gene related to poorer memory potential had to tax their brains harder to remember the same amount of information.
[2658] Papassotiropoulos, A., Stephan D. A., Huentelman M. J., Hoerndli F. J., Craig D. W., Pearson J. V., et al.
(2006). Common Kibra Alleles Are Associated with Human Memory Performance.
Science. 314(5798), 475 - 478.
http://www.eurekalert.org/pub_releases/2006-10/ttgr-rti101906.php
Protein found to inhibit conversion to long-term memory
In a study using genetically engineered mice, researchers have found that mice without a protein called GCN2 acquire new information that doesn’t fade as easily as it does in normal mice. After weak training on the Morris water maze, their spatial memory was enhanced, but it was impaired after more intense training. The researchers concluded that GCN2 may prevent new information from being stored in long-term memory, suggesting the conversion of new information into long-term memory requires both the activation of molecules that facilitate memory storage, and the silencing of proteins such as GCN2 that inhibit memory storage.
[949] Yoshida, M., Imataka H., Cuello C. A., Seidah N., Sossin W., Lacaille J-C., et al.
(2005). Translational control of hippocampal synaptic plasticity and memory by the eIF2[alpha] kinase GCN2.
Nature. 436(7054), 1166 - 1173.
http://www.eurekalert.org/pub_releases/2005-08/uom-mrp082905.php
Closing in on the genes involved in human intelligence
A genetic study claims to have identified two regions of the human genome that appear to explain variation in IQ. Previous research has suggested that between 40% and 80% of variation in human intelligence (as measured by IQ tests) can be attributed to genetic factors, but research has so far failed to identify these genes. The new study has identified specific locations on Chromosomes 2 and 6 as being highly influential in determining IQ, using data from 634 sibling pairs. The region on Chromosome 2 that shows significant links to performance IQ overlaps a region associated with autism. The region on Chromosome 6 that showed strong links with both full-scale and verbal IQ marginally overlapped a region implicated in reading disability and dyslexia.
[382] Posthuma, D., Luciano M., Geus E., Wright M., Slagboom P., Montgomery G., et al.
(2005). A Genomewide Scan for Intelligence Identifies Quantitative Trait Loci on 2q and 6p.
The American Journal of Human Genetics. 77(2), 318 - 326.
http://www.qimr.edu.au/news/index.html
Human cerebellum and cortex age in very different ways
Analysis of gene expression in five different regions of the brain's cortex has found that brain changes with aging were pronounced and consistent across the cortex, but changes in gene expression in the cerebellum were smaller and less coordinated. Researchers were surprised both by the homogeneity of aging within the cortex and by the dramatic differences between cortex and cerebellum. They also found that chimpanzees' brains age very differently from human brains; the findings cast doubt on the effectiveness of using rodents to model various types of neurodegenerative disease.
[951] Fraser, H. B., Khaitovich P., Plotkin J. B., Pääbo S., & Eisen M. B.
(2005). Aging and Gene Expression in the Primate Brain.
PLoS Biol. 3(9), e274 - e274.
http://www.eurekalert.org/pub_releases/2005-08/hu-hca072805.php
More light on a common developmental disorder
Chromosome 22q11.2 deletion syndrome is the most common genetic deletion syndrome, and causes symptoms such as heart defects, cleft palate, abnormal immune responses and cognitive impairments. Two related studies have recently cast more light on these cognitive impairments. Previously it was known that numerical abilities were impaired more than verbal skills. The new study found children with the chromosome deletion performed more poorly on experiments designed to test visual attention orienting, enumerating, and judging numerical magnitudes. All three tasks relate to how the children mentally represent objects and the spatial relationships among them, supporting previous arguments that such visual-spatial skills are a fundamental foundation to the later learning of counting and mathematics. The second study found that such children had changes in the shape, size and position of the corpus callosum, the main bridge between the two hemispheres.
[1139] Simon, T. J., Bearden C. E., Mc-Ginn D MD., & Zackai E.
(2005). Visuospatial and Numerical Cognitive Deficits in Children with Chromosome 22Q11.2 Deletion Syndrome.
Cortex. 41(2), 145 - 155.
[812] Simon, T. J., Ding L., Bish J. P., McDonald-McGinn D. M., Zackai E. H., & Gee J.
(2005). Volumetric, connective, and morphologic changes in the brains of children with chromosome 22q11.2 deletion syndrome: an integrative study.
NeuroImage. 25(1), 169 - 180.
http://www.eurekalert.org/pub_releases/2005-03/chop-lbt030205.php
Closing in on the genes involved in context learning
A study involving the worm C. elegans (whose genome has been completely sequenced) has demonstrated that even such simple animals demonstrate memory that is sensitive to context. In the study, the worms were trained in a salt medium to associate a particular smell with starvation. When placed in a different salt medium, the worms didn’t respond to the smell, but showed distaste when experiencing the smell in the context of the salt medium in which they were trained. More importantly, use of this animal has enabled the researchers to identify a genetic mutation that affects this type of memory. The next step will be to identify the specific gene involved in processing environmental cues.
[1072] Law, E., Nuttley W. M., & van der Kooy D.
(2004). Contextual Taste Cues Modulate Olfactory Learning in C. elegans by an Occasion-Setting Mechanism.
Current Biology. 14(14), 1303 - 1308.
http://www.eurekalert.org/pub_releases/2004-07/uot-eil072704.php
Some brains age more rapidly than others
Investigation of the patterns of gene expression in post-mortem brain tissue has revealed two groups of genes with significantly altered expression levels in the brains of older individuals. The most significantly affected were mostly those related to learning and memory. One of the most interesting, and potentially useful, findings, is that patterns of gene expression were quite similar in the brains of younger adults. Very old adults also showed similar patterns, although the similarity was less. But the greatest degree of individual variation occurred in those aged between 40 and 70. Some of these adults showed gene patterns that looked more like the young group, whereas others showed gene patterns that looked more like the old group. It appears that gene changes start around 40 in some people, but not in others. It also appears that those genes that are affected by age are unusually vulnerable to damage from agents such as free radicals and toxins in the environment, suggesting that lifestyle in young adults may play a part in deciding rate and degree of cognitive decline in later years.
[1335] Lu, T., Pan Y., Kao S-Y., Li C., Kohane I., Chan J., et al.
(2004). Gene regulation and DNA damage in the ageing human brain.
Nature. 429(6994), 883 - 891.
http://www.eurekalert.org/pub_releases/2004-06/chb-dgi060204.php
Could memory performance and spatial learning be genetically based?
A new rat study provides evidence that individual differences in some cognitive functions (specifically spatial navigation, in this experiment) may have a genetic basis.
[1267] Ruiz-Opazo, N., & Tonkiss J.
(2004). X-linked loci influence spatial navigation performance in Dahl rats.
Physiological Genomics. 16(3), 329 - 333.
http://www.eurekalert.org/pub_releases/2004-02/aps-cmp020404.php
Gene essential for development of normal brain connections discovered
After birth, learning and experience change the architecture of the brain dramatically. The structure of individual neurons, or nerve cells, changes during learning to accommodate new connections between neurons. Neuroscientists believe these structural changes are initiated when neurons are activated, causing calcium ions to flow into cells and alter the activity of genes. Now the first gene, CREST, known to mediate these changes in the structure of neurons in response to calcium, has been discovered. In the study, it was found that mice lacking this gene didn’t develop normally in response to sensory experience, and their brains, while normal at birth, later showed far less interconnectivity between neurons. The gene produces a protein that, in adult humans, is produced in the hippocampus. It is therefore speculated that the protein may be necessary for learning and memory storage. The discovery of this gene may have implications for certain types of learning disorders in humans.
[915] Aizawa, H., Hu S-C., Bobb K., Balakrishnan K., Ince G., Gurevich I., et al.
(2004). Dendrite development regulated by CREST, a calcium-regulated transcriptional activator.
Science (New York, N.Y.). 303(5655), 197 - 202.
http://www.eurekalert.org/pub_releases/2004-01/uoc--gef010804.php
Brain protein affecting learning and memory discovered
A significant new brain protein has been identified. Cypin is found throughout the body, but in the brain it now appears that it regulates neuron branching in the hippocampus. Such branching is thought to increase when learning occurs, and a reduction in branching is associated with certain neurological diseases. Discovery of this protein opens the possibility of new drug therapies for treating neurological disorders, and perhaps even memory-enhancing drugs.
[696] Akum, B. F., Chen M., Gunderson S. I., Riefler G. M., Scerri-Hansen M. M., & Firestein B. L.
(2004). Cypin regulates dendrite patterning in hippocampal neurons by promoting microtubule assembly.
Nat Neurosci. 7(2), 145 - 152.
http://www.eurekalert.org/pub_releases/2004-01/rtsu-rsd011204.php
http://news.independent.co.uk/world/science_medical/story.jsp?story=482567
Amphetamine helps or hinders cognitive function depending on your genes
Everyone inherits two copies of the catecho-O-methyltransferase (COMT) gene, that codes for the enzyme that metabolizes neurotransmitters like dopamine and norepinephrine. It comes in two common versions. One version, met, contains the amino acid methionine at a point in its chemical sequence where the other version, val, contains a valine. Depending on the mix of variants inherited, a person's COMT genes can be typed met/met, val/val, or val/met. People with the val/val variant appear to have reduced prefrontal dopamine activity and less efficient prefrontal information processing, along with slightly increased risk for schizophrenia. People with val/met have more efficient prefrontal function, and people with met/met the most efficient.
In a recent imaging study, 27 volunteers (10 val/val, 11 val/met, and 6 met/met) performed a variety of cognitive tasks that involved working memory and executive functioning, after taking either amphetamine or a placebo. Since amphetamine boosts dopamine activity in the prefrontal cortex, the researchers predicted that the drug would enable val/val types to boost their low level of dopamine and perform better on cognitive tasks that depend on the prefrontal cortex. On the other hand, those with met/met should be hindered by amphetamine. The study confirmed these predictions - val/val subjects on amphetamine performed comparably to met/met types in normal conditions, while met/met subjects on amphetamine performed worse than subjects with val/val types in normal conditions.
Amphetamines and other drugs that affect prefrontal dopamine systems are used to treat Attention Deficit Hyperactivity Disorder (ADHD), and other psychiatric illnesses, and some people respond better than others to these medications. About 15-20% of individuals in populations of European ancestry have the met/met COMT gene type.
[1292] Mattay, V. S., Goldberg T. E., Fera F., Hariri A. R., Tessitore A., Egan M. F., et al.
(2003). Catechol O-methyltransferase val158-met genotype and individual variation in the brain response to amphetamine.
Proceedings of the National Academy of Sciences of the United States of America. 100(10), 6186 - 6191.
http://www.eurekalert.org/pub_releases/2003-05/niom-gep050703.php
Gene linked to poor episodic memory
Brain derived neurotrophic factor (BDNF) plays a key role in neuron growth and survival and, it now appears, memory. We inherit two copies of the BDNF gene - one from each parent - in either of two versions. Slightly more than a third inherit at least one copy of a version nicknamed "met," which the researchers have now linked to poorer memory. Those who inherit the “met” gene appear significantly worse at remembering events that have happened to them, probably as a result of the gene’s effect on hippocampal function. Most notably, those who had two copies of the “met” gene scored only 40% on a test of episodic (event) memory, while those who had two copies of the other version scored 70%. Other types of memory did not appear to be affected. It is speculated that having the “met” gene might also increase the risk of disorders such as Alzheimer’s and Parkinson's.
[1039] Dean, M., Egan M. F., Kojima M., Callicott J. H., Goldberg T. E., Kolachana B. S., et al.
(2003). The BDNF val66met Polymorphism Affects Activity-Dependent Secretion of BDNF and Human Memory and Hippocampal Function.
Cell. 112(2), 257 - 269.
http://www.nih.gov/news/pr/jan2003/nimh-23.htm
http://www.eurekalert.org/pub_releases/2003-01/niom-hga012203.php
http://news.bbc.co.uk/1/hi/health/2687267.stm