Early Stress in Rats Bites Memory Later On: Inadequate care to young animals delivers delayed hit to the brain

The stress of experiencing inadequate childhood care rebounds with a brain-altering, memory-sapping vengeance in middle age, at least in laboratory rats, a new study indicates.

Neuroscientist Tallie Z. Baram of the University of California, Irvine and her colleagues have obtained the first evidence that young animals exposed to such stress later in life suffer memory declines accompanied by disrupted cell communication in the hippocampus, a brain region critical for learning and memory.

Although no nonhuman animal provides an exact behavioral model of child abuse (SN: 7/2/05, p. 5: Mother Knows Worst: Abusive parenting spans generations in monkeys), the findings raise the possibility that the emotional toll of child abuse and neglect accelerates memory loss in adults, the researchers report in the Oct. 12 Journal of Neuroscience.

“I think our model is the one that most closely approximates the human condition because we do not separate pups from their mothers,” Baram says. “We produce a situation where the mother is present, but her behavior is abnormal.”

Baram’s group tracked 24 newborn male rats, each housed in a cage with its mother. On the second day after birth and for the week that followed, half the animals were placed in cages with nothing but a paper towel that mothers could use to construct a nest. Under these sparse conditions, the mothers nursed and groomed their pups infrequently.

The remaining rats lived in cages with plenty of wood chips for building nests, and the mothers nursed and groomed their pups often.

After a week of poor care, young rats displayed elevated stress-hormone levels and other physical signs of chronic stress. However, by 4 to 5 months of age—young adulthood for a rat—the same animals no longer exhibited these stress markers.

At that point, formerly stressed rats performed as well as the others did on two memory tests. One test assessed memory for the location of a hidden platform in a vat of water; the other probed for recognition of items, such as a padlock, presented alone on one day and with a novel object the next day.

Laboratory tests conducted on hippocampus slices from half the rats in each group showed similar cell features and electric activity.

However, in late middle age—about 1 year for a rat—brain and behavioral deficits appeared for the early-stress rats. Their memory scores dropped markedly. Hippocampus analyses revealed disturbed cell firing, depressed cell responses to electric stimulation, dwindling numbers of synapses, and an expansion of a class of cells called mossy fibers that may disrupt overall hippocampus function.

Neuroscientist Robert M. Sapolsky of Stanford University calls the new experiment “a beautiful study” of delayed effects of early-life stress on the brain and memory.

“We need to find out how these remarkable changes occur,” Baram says.

Further experiments should examine whether placing stressed rats in enriched environments offsets later neural and memory problems, remarks neuroscientist William T. Greenough of the University of Illinois at Urbana-Champaign.