Is Your Hippocampus On A Hippo Campus?

Well, if you have half a mind, you have a whole hippocampus. It’s the part of the brain in charge of long-term memory (Where are the car keys?) and spatial relations (Will this car fit into that parking space?). It’s shaped like a horseshoe and straddles both of the brain’s hemispheres.  It works like a book’s index, where it consolidates new memories and helps to retrieve them later on. It’s the search engine of the brain. Depending on the perceived importance of a task or episode, learning and remembering may require only a single exposure, after which the memory trace either disappears or consolidates into the long-term cache.

Neuroscientists use rats and mice in their investigations. This is an intriguing proposition to non-scientists, who are not aware that all mammalian hippocampi tend to work the same way. The anatomy, physiology and genetics of mice and rats are strikingly similar to humans’, where 95% of their genome is shared. Rats are the subjects of study because they mature quickly and have brains large enough to make observations easy. About the only part of the brain that separates us from rats is the prefrontal cortex with its higher-level thought processes, such as setting goals, reminiscing, and inhibiting irrelevant functions.

To exemplify the parallels, scientists exposed rats to environments that were enriched, standard or impoverished. Later, their brains were examined, finding that the structures of the enriched had more and longer dendrites, which afford more opportunity for learning and memory. Post-mortem brain tissue of college-educated humans was compared with that of lesser-educated humans, also finding more and longer dendrites, leading to the conclusion that brain changes—multiplying connections—occur in response to a complex environment (Jacobs, 1993) (Diamond, 1972, 2001).

Diets high in saturated fats and refined sugars may cause changes in the brain that fuel the overconsumption of foods that make people gain weight. Such cerebral alterations happen in spite of the mental stimulation that encourages positive brain development.  In this vicious cycle lies a possible explanation why obesity is so hard to overcome—the brain says to keep eating while blocking thoughts of self-control. Lab rats offered unlimited access to a high-energy diet (high-fat/high-calorie) fared much worse in memory tests than their cohorts fed the opposite, indicating to researchers a change in functionality of the hippocampus (Davidson, 2012). In effect, they “forgot” to stop eating. It appears that saturated fats and refined sugars interfere with messages that tell you when to rein it in. Diet-induced obesity has such deleterious effects on the hypothalamus that more time becomes necessary to learn new tasks and more errors occur along the way (Valladolid-Acebes, 2011).

Excess energy intake, especially if combined with a sedentary lifestyle, is associated with a number of conditions that include cardiovascular disease, insulin resistance/diabetes, and some cancers. But this elevated risk of cognitive decline in later life is something that can be contained with conscious effort. Public health messages have decried the scourge of obesity for a time, but have never made known its association with mental dilapidation (Sabia, 2009). For those memories maintained by the hippocampus, the edge goes to people of normal weight (Nilsson, 2009).

Neural plasticity refers to the change in structure, function and organization of neurons in response to new learning experiences, where nerve connection are added based on outside stimuli, as mentioned earlier. Some researchers have reported sex differences in response to high-fat and high-sucrose diet, where females are less vulnerable to its impact (Hwang, 2010). This relative immunity from cognitive compromise does little for connubial bliss.  We need to note, though, that some types of learning and memory may be affected by diet more than others. For example, memory retention but not acquisition may suffer. We also know that sugar intake has an effect on triglycerides, the reduction of which could reduce cognitive impairment while improving cardiac health. That may be worth a look.

There is considerable data from animal studies and somewhat more limited data from human studies to support the premise that excess energy intake drives cognitive dysfunction and disrupts neural plasticity. Because of individual differences—genetics, exercise, lifestyle—it’s not likely that science can make recommendations about the ideal energy intake, although an upper limit of 2200 calories for men and 2000 calories for women has been proposed. Meanwhile, exercise is recognized as a major factor in mediating the adverse effect of sloppy diet on cognitive wherewithal (van Praag, 2009), followed by increase in social interaction or engaging in challenging activities such as some hobbies afford (Bennett, 2006). So, now when you watch what you eat, watch what you eat. Eating to live is not the same as living to eat.

Barberger-Gateau P, Raffaitin C, Letenneur L, Berr C, Tzourio C, Dartigues JF, Alpérovitch A. Dietary patterns and risk of dementia: the Three-City cohort study. Neurology. 2007 Nov 13;69(20):1921-30.

Bennett DA, Schneider JA, Tang Y, Arnold SE, Wilson RS. The effect of social networks on the relation between Alzheimer's disease pathology and level of cognitive function in old people: a longitudinal cohort study. Lancet Neurol. 2006 May;5(5):406-12.

Terry L. Davidson, Andrew Monnot, Adelai U. Neal, Ashley A. Martin, J. Josiah Horton, Wei Zheng The effects of a high-energy diet on hippocampal-dependent discrimination performance and blood–brain barrier integrity differ for diet-induced obese and diet-resistant rats Physiology & Behavior. Volume 107, Issue 1, 20 August 2012, Pages 26–33

DeKosky ST, Abrahamson EE, Ciallella JR, Paljug WR, Wisniewski SR, Clark RS, Ikonomovic MD. Association of increased cortical soluble abeta42 levels with diffuse plaques after severe brain injury in humans. Arch Neurol. 2007 Apr;64(4):541-4.

Marian C. Diamond, Mark R. Rosenzweig, Edward L. Bennett, Bernice Lindner, Lennis Lyon Effects of environmental enrichment and impoverishment on rat cerebral cortex Journal of Neurobiology. Volume 3, Issue 1, pages 47–64, 1972

Diamond MC. Response of the brain to enrichment. An Acad Bras Cienc. 2001 Jun;73(2):211-20.

Carol E. Greenwood, Gordon Winocur† Learning and memory impairment in rats fed a high saturated fatdiet Behavioral and Neural Biology. Volume 53, Issue 1, January 1990, Pages 74–87

Hendrickx H, McEwen BS, Ouderaa F. Metabolism, mood and cognition in aging: the importance of lifestyle and dietary intervention. Neurobiol Aging. 2005 Dec;26 Suppl 1:1-5. Epub 2005 Nov 14.

Hwang LL, Wang CH, Li TL, Chang SD, Lin LC, Chen CP, Chen CT, Liang KC, Ho IK, Yang WS, Chiou LC. Sex differences in high-fat diet-induced obesity, metabolic alterations and learning, and synaptic plasticity deficits in mice. Obesity (Silver Spring). 2010 Mar;18(3):463-9. Epub 2009 Sep 3.

Jacobs B, Schall M, Scheibel AB. A quantitative dendritic analysis of Wernicke's area in humans. II. Gender, hemispheric, and environmental factors. J Comp Neurol. 1993 Jan 1;327(1):97-111.

Jurdak N, Lichtenstein AH, Kanarek RB. Diet-induced obesity and spatial cognition in young male rats. Nutr Neurosci. 2008 Apr;11(2):48-54.

Kosari S, Badoer E, Nguyen JC, Killcross AS, Jenkins TA. Effect of western and high fat diets on memory and cholinergic measures in the rat. Behav Brain Res. 2012 Nov 1;235(1):98-103. Epub 2012 Jul 20.

Launer LJ, Ross GW, Petrovitch H, Masaki K, Foley D, White LR, Havlik RJ. Midlife blood pressure and dementia: the Honolulu-Asia aging study. Neurobiol Aging. 2000 Jan-Feb;21(1):49-55.

Mark P. Mattson The Impact of Dietary Energy Intake on Cognitive Aging Front Aging Neurosci. 2010; 2: 5.

Messier C, Whately K, Liang J, Du L, Puissant D. The effects of a high-fat, high-fructose, and combination diet on learning, weight, and glucose regulation in C57BL/6 mice. Behav Brain Res. 2007 Mar 12;178(1):139-45. Epub 2006 Dec 17.

Mielke JG, Nicolitch K, Avellaneda V, Earlam K, Ahuja T, Mealing G, Messier C. Longitudinal study of the effects of a high-fat diet on glucose regulation, hippocampal function, and cerebral insulin sensitivity in C57BL/6 mice. Behav Brain Res. 2006 Dec 15;175(2):374-82. Epub 2006 Nov 1.

Molteni R, Barnard RJ, Ying Z, Roberts CK, Gómez-Pinilla F. A high-fat, refined sugar diet reduces hippocampal brain-derived neurotrophic factor, neuronal plasticity, and learning. Neuroscience. 2002;112(4):803-14.

Nilsson LG, Nilsson E. Overweight and cognition. Scand J Psychol. 2009 Dec;50(6):660-7.

Sabia S, Kivimaki M, Shipley MJ, Marmot MG, Singh-Manoux A. Body mass index over the adult life course and cognition in late midlife: the Whitehall II Cohort Study. Am J Clin Nutr. 2009 Feb;89(2):601-7. Epub 2008 Dec 10.

Valladolid-Acebes I, Stucchi P, Cano V, Fernández-Alfonso MS, Merino B, Gil-Ortega M, Fole A, Morales L, Ruiz-Gayo M, Del Olmo N. High-fat diets impair spatial learning in the radial-arm maze in mice. Neurobiol Learn Mem. 2011 Jan;95(1):80-5. Epub 2010 Nov 17.

van Praag H. Exercise and the brain: something to chew on. Trends Neurosci. 2009 May;32(5):283-90. Epub 2009 Apr 6.

Wu A, Molteni R, Ying Z, Gomez-Pinilla F. A saturated-fat diet aggravates the outcome of traumatic brain injury on hippocampal plasticity and cognitive function by reducing brain-derived neurotrophic factor. Neuroscience. 2003;119(2):365-75.