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Researchers identify human memory gene
Newsdesk
Researchers identify human memory gene
Fiona Hansen/PA/EMPICS
The printed journal includes an image merely for illustration Eight-time World Memory Champion Dominic O’Brien
An international team of researchers has uncovered a gene that may have a key role in memory function in human beings. These findings could lead to a better understanding of the memory process and may ultimately lead to new strategies to help people with memory problems, the researchers suggest. To identify genes related to memory performance, Andreas Papassotiropoulos (University of Zurich, Switzerland), and co-workers scanned the whole genome of 341 healthy Swiss individuals aged 18–48 years for more than 500 000 single nucleotide polymorphisms.
The individuals were stratified into four groups according to their performance on a word-retrieval memory task. The researchers found that individuals who carried a particular KIBRA allele were 24% better than non-carriers at recalling words 5 min after being asked to remember them, and 19% better at remembering the words after 24 h. The KIBRA variant was further tested in two additional independent cohorts: 256 cognitively normal individuals aged 20–81 years from the USA and 424 young adults aged 18– 28 years from Switzerland. In both cohorts, the KIBRA variant was again associated with better performance on memory tests (Science 2006; 314: 475–78). The researchers then went on to show that KIBRA was expressed at high levels in memory-related structures in the human brain, including the hippocampus and temporal lobe. Furthermore, non-carriers of the variant showed increased activation in the hippocampus during memory tests compared with carriers, suggesting that non-carriers need to work harder to achieve the same level of memory retrieval.
“KIBRA is the first memory-related gene identified by genome-wide scanning”, Papassotiropoulos told The Lancet Neurology. “One of the important issues with KIBRA is that it is a gene we would never have studied in a hypothesis-driven approach. Now that we know of its existence, we can track the entire KIBRA-related pathway to understand human memory better and ultimately to help people with memory problems.” Papassotiropoulos adds that it is premature to tell whether KIBRA will contribute to the development of better treatments for memory disorders. “On the other hand”, he adds, “we now know that KIBRA may be a modulator of synaptic plasticity, it may interact with a protein kinase (PKCzeta) that has been implicated in memory formation and long-term potentiation, and it may serve as a calcium sensor in vesicle exocytosis, bolstering the communication between brain cells. We are excited about the chance to use this information to identify promising memory-modulating compounds.”
Helen Frankish
The crossroads of metabolic deficits and neurodegeneration Clinical signs of disturbed metabolism are common in neurodegenerative disorders. Neurons are extremely sensitive to disruptions in their energy provision, which can trigger diverse pathological cascades. New research reveals that the molecular link between neurodegeneration and metabolic defects may lie on PGC-1α, a transcriptional coactivator responsible for proper mitochondrial function. While working with a transgenic mouse model for Huntington’s disease (HD), Albert La Spada and colleagues (University of Washington, Seattle, WA, USA) were 1008
intrigued by the animals’ inability to maintain normal thermoregulation and by the odd appearance of their brown adipose tissue, which mediates temperature responses. They found that, unlike their wildtype littermates, cold-challenged mice did not show upregulation in concentrations of UCP-1, a mitochondrial protein required for adaptative thermogenesis. PGC1α activates UCP-1 transcription, which in turn leads to the increased sympathetic tone characteristic of the adaption to cold temperatures. The researchers found that disruptions
in the circuit were not confined to the brown adipose tissue of HD mice: “The disruption of the PGC-1α transcription pathway occurs also in striatal brain tissue taken from HD mice and in the caudate nucleus of patients with HD”, explains Victor Pineda, an author in the study (Cell Metab 2006; published online Oct 19. DOI:10.1016/j.cmet.2006.10.004). In patients with HD, which is caused by the expansion of CAG trinucleotide repeats in the huntingtin gene, weight loss is often accompanied by abnormal glucose and lactate metabolism. Mutant huntingtin
http://neurology.thelancet.com Vol 5 December 2006
Researchers identify human memory gene
Fiona Hansen/PA/EMPICS
The printed journal includes an image merely for illustration Eight-time World Memory Champion Dominic O’Brien
An international team of researchers has uncovered a gene that may have a key role in memory function in human beings. These findings could lead to a better understanding of the memory process and may ultimately lead to new strategies to help people with memory problems, the researchers suggest. To identify genes related to memory performance, Andreas Papassotiropoulos (University of Zurich, Switzerland), and co-workers scanned the whole genome of 341 healthy Swiss individuals aged 18–48 years for more than 500 000 single nucleotide polymorphisms.
The individuals were stratified into four groups according to their performance on a word-retrieval memory task. The researchers found that individuals who carried a particular KIBRA allele were 24% better than non-carriers at recalling words 5 min after being asked to remember them, and 19% better at remembering the words after 24 h. The KIBRA variant was further tested in two additional independent cohorts: 256 cognitively normal individuals aged 20–81 years from the USA and 424 young adults aged 18– 28 years from Switzerland. In both cohorts, the KIBRA variant was again associated with better performance on memory tests (Science 2006; 314: 475–78). The researchers then went on to show that KIBRA was expressed at high levels in memory-related structures in the human brain, including the hippocampus and temporal lobe. Furthermore, non-carriers of the variant showed increased activation in the hippocampus during memory tests compared with carriers, suggesting that non-carriers need to work harder to achieve the same level of memory retrieval.
“KIBRA is the first memory-related gene identified by genome-wide scanning”, Papassotiropoulos told The Lancet Neurology. “One of the important issues with KIBRA is that it is a gene we would never have studied in a hypothesis-driven approach. Now that we know of its existence, we can track the entire KIBRA-related pathway to understand human memory better and ultimately to help people with memory problems.” Papassotiropoulos adds that it is premature to tell whether KIBRA will contribute to the development of better treatments for memory disorders. “On the other hand”, he adds, “we now know that KIBRA may be a modulator of synaptic plasticity, it may interact with a protein kinase (PKCzeta) that has been implicated in memory formation and long-term potentiation, and it may serve as a calcium sensor in vesicle exocytosis, bolstering the communication between brain cells. We are excited about the chance to use this information to identify promising memory-modulating compounds.”
Helen Frankish
The crossroads of metabolic deficits and neurodegeneration Clinical signs of disturbed metabolism are common in neurodegenerative disorders. Neurons are extremely sensitive to disruptions in their energy provision, which can trigger diverse pathological cascades. New research reveals that the molecular link between neurodegeneration and metabolic defects may lie on PGC-1α, a transcriptional coactivator responsible for proper mitochondrial function. While working with a transgenic mouse model for Huntington’s disease (HD), Albert La Spada and colleagues (University of Washington, Seattle, WA, USA) were 1008
intrigued by the animals’ inability to maintain normal thermoregulation and by the odd appearance of their brown adipose tissue, which mediates temperature responses. They found that, unlike their wildtype littermates, cold-challenged mice did not show upregulation in concentrations of UCP-1, a mitochondrial protein required for adaptative thermogenesis. PGC1α activates UCP-1 transcription, which in turn leads to the increased sympathetic tone characteristic of the adaption to cold temperatures. The researchers found that disruptions
in the circuit were not confined to the brown adipose tissue of HD mice: “The disruption of the PGC-1α transcription pathway occurs also in striatal brain tissue taken from HD mice and in the caudate nucleus of patients with HD”, explains Victor Pineda, an author in the study (Cell Metab 2006; published online Oct 19. DOI:10.1016/j.cmet.2006.10.004). In patients with HD, which is caused by the expansion of CAG trinucleotide repeats in the huntingtin gene, weight loss is often accompanied by abnormal glucose and lactate metabolism. Mutant huntingtin
http://neurology.thelancet.com Vol 5 December 2006