Tuesday, April 12, 2016

The maternal environment can impact fetal development

D. Bilbo and Verne Tsang did research on the rat about effect of maternal obesity on the

offspring. In this research, rats were fed with high fat diet before and during the pregnancy. After

that newborns were examined for microglia and microglia activation factors. As a results, it was

found large amount of microglia activation markers and microglia itself in hippocampus of the

brain. Consequently, offspring of high fat diet had inflammation in the hypothalamus and the

peripheral nervous system. [4]

Probable mechanism is that the high fat concentration induce microglia activation proteins in the

brain. For example, it can induce expression of CD40 Ligand, which is essential in microglia

inflammation and activation. As a result, CD40 Ligand recruit and activate microglia in the

hypothalamus. Consequently, accumulation of microglia in hypothalamus can lead to brain

inflammation. From this, we can conclude that maternal obesity can probably had negative effect

on brain development, because it can lead to brain inflammation.

In addition, offspring of mice with high fat diet had an increased concentration of Interleukin-1

in the brain. This interleukin-1 can consequently activates lymphocytes and neutrophils, which

can lead to brain inflammation. [4]

According to the figure 1 maternal high fat diet in the mice leads to the offspring with high lipid

concentration in the blood. This consequently lead to accumulation of Neuroepithelial Stem

Cells  in hypothalamic area of the third ventricle. This neuroepithelial stem cells then migrate to

the area of PVN and PFLH.  Neurons in this area mainly produce the orexigenic peptide. The

orexigenic peptide is responsible for appetite stimulation. [5] Consequently, newborn eat a lot

and gain weight.

Maternal over nutrition or obesity can lead to insulin resistance in the offspring. Therefore,

insulin resistance can lead to some cognitive malfunction. More importantly insulin resistance or

diabetes type-2 can lead to Alzheimer's disease. Probable mechanism is that diabetes can lead to

Azat Duisembay

vascular dementia, which may affect blood flow to the brain. Then, reduced blood flow with

diabetes can lead to little cognitive dysfunction. Then, cognitive dysfunction could lead to

Alzheimer’s disease. [1]

Obesity can lead to gestational diabetes. According to Malik and Ripple gestational diabetes can

lead to insignificant motor retardation and inattention. Motor retardation and inattention is

strongly correlated with sleep and fatigue. Sleep and fatigue is associated with hypothalamus. [2]

According to another article by Page and Malik a high fat diet of mother before and during the

pregnancy can alter gene expression in developing brain of the fetus and in particularly it can

alter gene expression in hypothalamus. It was found that babies had increased concentration of

NPY neurotransmitter, leptin receptor ObRb and signal transducer STAT3. [3] Consequently,

overexpression of NPY neurotransmitter, leptin receptor ObRb and signal transducer STAT3

lead to abnormal functioning of hypothalamus. As a result, inattention and insignificant motor

retardation appear.

Reference:

[1]Diabetes and cognitive decline. Alzheimer association. (2013)

[2] Malik RE, Ripple JA, Anday EK. School-age children born to diabetic mothers and to

mothers with gestational diabetes exhibit a high rate of inattention and fine and gross motor

impairment. (2009)

[3]Kathleen C. Page , Raleigh E. Malik , Joshua A. Ripple , Endla K. Anday, American Journal

of Physiology Maternal and postweaning diet interaction alters hypothalamic gene expression

and modulates response to a high-fat diet in male offspring.(2008)

[4] Staci D. Bilbo and Verne Tsang, The FASEB Journal Enduring consequences of maternal obesity for

brain inflammation and behavior of offspring (2010)

[5] Guo-Qing Chang, Valeriya Gaysinskaya, Olga Karatayev, and Sarah F. Leibowitz journal of

neuroscience,  Maternal High-Fat Diet and Fetal Programming: Increased Proliferation of

Hypothalamic Peptide-Producing Neurons That Increase Risk for Overeating and Obesity

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