"Long before it's in the papers"
December 07, 2011

RETURN TO THE WORLD SCIENCE HOME PAGE

Drug may undo aging-associated brain changes in animals

Dec. 7, 2011
Courtesy of the Society for Neuroscience
and World Science staff

Drugs that af­fect the lev­els of an im­por­tant brain pro­tein re­verse cel­lu­lar changes in rat brains seen dur­ing ag­ing, ac­cord­ing to a new an­i­mal stu­dy. Sci­en­tists say the find­ings, pub­lished in the Dec. 7 is­sue of The Jour­nal of Neu­ro­sci­ence, could one day aid in the de­vel­op­ment of drugs that boost cog­ni­tive func­tion in old­er peo­ple.

Aging-related mem­o­ry loss is as­so­ci­at­ed with a de­te­riora­t­ion in synaps­es—con­nections be­tween brain cell­s—in brain re­gions tied to learn­ing and mem­o­ry, in­clud­ing a crit­i­cal struc­ture called the hip­po­cam­pus. 

Re­cent stud­ies sug­gested that a chem­i­cal pro­cess that con­trols wheth­er genes are turned on, known as his­tone ac­e­tyla­t­ion, af­fects this pro­cess. Spe­cif­ic­ally, it af­fects brain cells’ abil­ity to al­ter the strength and struc­ture of their con­nec­tions for in­forma­t­ion stor­age, a pro­cess known as syn­ap­tic plas­ticity, which is a cel­lu­lar sig­na­ture of mem­o­ry.

In the new work, Cui-Wei Xie of the Uni­vers­ity of Cal­i­for­nia, Los An­ge­les, and col­leagues found that com­pared with young­er rats, old rats’ hip­pocampi have less of a pro­tein that pro­motes syn­ap­tic plas­ticity, called brain-derived neu­ro­troph­ic fac­tor. These brains al­so show less his­tone ac­e­tyla­t­ion of the gene for pro­duc­ing that pro­tein. 

By treat­ing the hip­po­cam­pal tis­sue from old­er an­i­mals with a drug that in­creased his­tone ac­e­tyla­t­ion, they were able to re­store the pro­tein’s pro­duc­tion and re­turn syn­ap­tic plas­ticity to lev­els found in young­er an­i­mals.

“These find­ings shed light on why synapses be­come less ef­fi­cient and more vulnera­ble to im­pair­ment dur­ing ag­ing,” said Xie, who led the stu­dy. “Such knowl­edge could help de­vel­op new drugs for cog­ni­tive ag­ing and ag­ing-related neu­rode­gen­er­a­tive dis­eases, such as Alzheimer’s dis­ease,” she added.

“It ap­pears that life­long shifts in gene regula­t­ion steadily de­prive the brain of a key growth fac­tor and cause a col­lapse of the ‘machin­ery’ sup­port­ing mem­o­ry, cog­ni­tion, and the vi­a­bil­ity of neu­rons,” said Gary Lynch, a syn­ap­tic plas­ticity ex­pert at the Uni­vers­ity of Cal­i­for­nia, Ir­vine. “The very good news sug­gested by this study is that it may be pos­si­ble to re­verse these ef­fects.”

* * *

Drugs that affect the levels of an important brain protein reverse cellular changes in rat brains seen during aging, according to a new animal study. Scientists say the findings, published in the Dec. 7 issue of The Journal of Neuroscience, could one day aid in the development of new drugs that enhance cognitive function in older people. Aging-related memory loss is associated with a deterioration in synapses—connections between brain cells—in brain regions tied to learning and memory, including a critical structure called the hippocampus. Recent studies suggested that a chemical process that controls whether genes are turned on, known as histone acetylation, affects this process. Specifically, it affects brain cells’ ability to alter the strength and structure of their connections for information storage, a process known as synaptic plasticity, which is a cellular signature of memory. In the study, Cui-Wei Xie of the University of California, Los Angeles, and colleagues found that compared with younger rats, old rats’ hippocampi have less of a protein that promotes synaptic plasticity, called brain-derived neurotrophic factor. These brains also show less histone acetylation of the gene for producing that protein. By treating the hippocampal tissue from older animals with a drug that increased histone acetylation, they were able to restore the protein’s production and return synaptic plasticity to levels found in younger animals. “These findings shed light on why synapses become less efficient and more vulnerable to impairment during aging,” said Xie, who led the study. “Such knowledge could help develop new drugs for cognitive aging and aging-related neurodegenerative diseases, such as Alzheimer’s disease,” she added. “It appears that lifelong shifts in gene regulation steadily deprive the brain of a key growth factor and cause a collapse of the ‘machinery’ supporting memory, cognition, and the viability of neurons,” said Gary Lynch, a synaptic plasticity expert at the University of California, Irvine. “The very good news suggested by this study is that it may be possible to reverse these effects.”