Embryo development

Genetic programming of hypothalamic neurons regulates food intake and body weight

gettingwell4 2-3 stars Required further work, Brain development, Hypothalamus, Limbic system ,

These 2015 Michigan/Argentinian fish and rodent studies were of the genetic programming of specific neurons in the hypothalamus. The study linked below found:

“Food intake and body weight regulation depend on proper expression of the gene” in these neurons.

In a second study released at the same time from the same researchers:

“The researchers found that the two enhancers act in ways that complement one another, both encouraging the expression of the Pomc gene at key times. One of the two is found in the same form among all mammals, the other among all placental mammals – suggesting that they’ve been kept intact throughout the evolutionary process.”

Genetic programming of these neurons begins during early brain development. One of the researchers said:

“This work represents the first example of a neuron-specific gene in vertebrates where we have found both the enhancers and a shared transcription factor that control gene expression in the developing brain and then throughout the life span of the adult.”

The first study showed that if the genetic expression of these hypothalamic neurons was disrupted, the individual lost control of their eating (hyperphagia) and the usual result was severe obesity:

“We don’t know, but we think it likely, that it [regulation of these specific hypothalamic neurons in humans] may be similar to the mouse model, where its role is like a dial, with a linear relationship between the amount of Pomc [the gene] expression and the degree of obesity.”

I hope that when extending this research to humans, the researchers don’t exclude emotional content like most studies involving areas of the limbic system have done. Everyone has feelings intermixed with eating and foods. It’s a great disservice to have publicly funded studies not include aspects of emotion that could potentially help people.

http://www.pnas.org/content/112/15/E1861.full “Islet 1 specifies the identity of hypothalamic melanocortin neurons and is critical for normal food intake and adiposity in adulthood”

Epigenetic DNA methylation and demethylation with the developing fetus

gettingwell4 5+ stars Premium, Brain development, Cortisol, Epigenetics, Hypothalamus, Limbic system, Neurochemicals, Oxytocin, Serotonin , ,

This extremely dense and informative 2014 UK summary study provided details about genomic imprinting:

“An unusual epigenetic process in that it is heritable and results in autosomal gene expression according to parent of origin.”

Several notes of interest:

  • Figure 3 had a fascinating sketch of how the fetus caused the mother’s hypothalamus to:

    “Determine forward maternal planning by directing/orchestrating maternal physiology and postnatal maternalism to synchronize with development of the fetus.”

  • Figure 4 followed up with a flowchart of how – with a female fetus – coexistence of three matrilineal generations in the pregnant female (her, the fetus, and the grandmother’s influence on the developing fetus’ ovarian oocytes) enabled intergenerational forward planning.
  • The study briefly noted significance of genomic imprinting on male sexual behavior, where, if processes didn’t proceed normally at this early stage of a male fetus’ development, could result in suboptimal adult behavior that didn’t change with experience.

F4.large

I’ll quote a few other unrelated passages that caught my eye.

“Reproductive success of mammals also places a considerable burden on matrilineal time and energy, with some 95% of mammalian female adult life committed to pregnancy, lactation, and maternal care.

Offspring that receive optimal nourishment and improved maternal care will be predisposed to develop a hypothalamus that is both genetically and epigenetically predisposed to this same type of good mothering.

The fetus controls its own destiny in times of acute starvation, especially in the last trimester of pregnancy, by short-term sacrifice of its placenta to preserve resources critical for brain development.”

http://www.pnas.org/content/112/22/6834.full “Genomic imprinting, action, and interaction of maternal and fetal genomes”

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Dr. Arthur Janov interview on his 2011 book Life Before Birth: The hidden script that rules our lives

gettingwell4 4-5 stars Advanced knowledge, Brain development, Cerebrum, Cortisol, Epigenetics, Limbic system, Lower brain, Neurochemicals, Primal Therapy, Stress, Telomeres , , , , , ,

Dr. Arthur Janov’s 2011 book “Life Before Birth: The hidden script that rules our lives” describes problems that start in the earliest parts of our lives, when epigenetic changes due to trauma in the womb affect our development.

“The science has changed. When I first started out 44 years ago, there was nobody who could understand it, or agree, especially the professionals. Now all, or a great deal of the current research, is backing up everything I say.

I’m saying that this therapy is really a matter of life and death now. I should probably start at the beginning and say that there’s trauma in the womb. We need to set back the clock so that we take account of trauma that occurs while our mother is carrying that has lifelong consequences for how long we live, for example. There’s a current research study that shows that as you get more traumatized in the womb, your life expectancy is much shorter.

When you get rid of the childhood pain that happened way back when – and there are ways to do it – you will live much longer. So truly, a proper therapy now is a matter of life and death. Not only because your life expectancy is shorter when you have trauma, but you get sick earlier, you have diabetes, Alzheimer’s, all kinds of diseases on your way to your death, which makes life very uncomfortable.

But that’s just part of what we do. The idea is that we found a way to take the pain out of the system, going all the way back. And what we’re finding is that pain starts way, way earlier than we thought.

I used to think that the greatest point was the birth trauma. Well that’s no longer true. Way before the birth trauma there are traumas from the smoking mothers, the anxious mothers, the depressed mothers, that have lifelong effects on the baby, the offspring.”

“https://www.youtube.com/watch?v=dbUhjZhpEyct”

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How to make a child less capable even before they are born: stress the pregnant mother-to-be

gettingwell4 4-5 stars Advanced knowledge, Brain development, Cortisol, Epigenetics, Hypothalamus, Limbic system, Neurochemicals, Primal Therapy, Stress, Testosterone , ,

This 2014 rodent study showed how to make a less-capable pup by stressing the mother early in gestation. The study centered on a placental enzyme (OGT) that translates a mother’s stress into neuroprogramming of her developing fetus.

One finding was that this enzyme was less plentiful when the fetus was male compared with female.

Another finding was that the enzyme was less plentiful when the mother was stressed early in gestation, compared with unstressed mothers.

Informed by the first two findings, the researchers studied the placentae of male pups where the mother was stressed early in gestation. They found that these placentae had lower levels of an enzyme (Hsd17b3) that converts the precursor androstenedione into testosterone.

The resultant finding was that the male pups of stressed mothers had lower levels of testosterone than the control group of male pups.

A fourth finding was that offspring of both sexes born with a placenta where the OGT enzyme was less plentiful had 10-20% less body weight, a condition that developed after weaning. The researchers attributed this finding to reduced mitochondrial function in the hypothalamus compared with normal mice.

http://www.pnas.org/content/111/26/9639.full “Targeted placental deletion of OGT recapitulates the prenatal stress phenotype including hypothalamic mitochondrial dysfunction”

Sex hormone exposure to the developing female fetus causes infertility in adulthood

gettingwell4 4-5 stars Advanced knowledge, Brain development, Epigenetics, Hypothalamus, Limbic system, Testosterone ,

This 2014 rodent study was of polycystic ovarian syndrome, which is the leading cause of human female infertility.

The researchers could reliably induce this disease in mice while they were still fetuses, but effects didn’t manifest until adulthood! The inducement method exposed the developing female fetuses to androgens such that their testosterone concentration was significantly increased.

Comparing this study with How mothers-to-be program lifelong low testosterone into their unborn male children, we can see that in early development:

  • too much testosterone for a female fetus and
  • too little testosterone for a male fetus

both have lifelong ill effects.

http://www.pnas.org/content/112/2/596.full “Enhancement of a robust arcuate GABAergic input to gonadotropin-releasing hormone neurons in a model of polycystic ovarian syndrome”

Problematic research that excluded the most influential human epigenetic environments

gettingwell4 < 0 Detracted from science, Epigenetics ,

This 2014 ivy league human study found that what appeared to be genetic links may have been epigenetic responses to our environment.

Curiously, none of the news articles covering this study highlighted the lack of the most influential environments on epigenetic DNA changes:

  • The mother’s prenatal environment provided for the fetus, and
  • The family environment during infancy and early childhood.

This omission may have been because the study intentionally didn’t support such an interpretation. Here’s a partial explanation from the study’s supplementary material of the “family fixed-effects model” the researchers developed:

“The family fixed-effects model blocks both genetic factors and parental characteristics/behaviors that are common to family members (e.g., siblings), including unmeasured factors; therefore, from the perspective of confounding, the fixed-effect specification is preferred.”

When the preferred model blocked the most important environments in which epigenetic DNA changes occur, what environments remained?

“These results suggest genetic influences on complex traits like obesity can vary over time, presumably because of global environmental changes that modify allelic penetrance.”

Although a finding attributing “global environmental changes” made more funding available to the researchers, it was rightly an outlier from the majority of epigenetic studies.

This finding made me start a negative rating for studies that DETRACT from science!

Why was the reviewer okay with the study’s model omitting the most important factors in human development? The study’s model defined away both the:

  • Out-of-favor genetic factors, and the
  • Predominant but nonpolitically-correct epigenetic factors

in order to manufacture a politically-correct epigenetics meme!

How else to interpret this statement, if not intended to generate a meme?

“Our results underscore the importance of interpreting any genetic studies with a grain of salt and leave open the possibility that new genetic risk factors may be seen in the future due to different genetically driven responses to our ever-changing environment.”

http://www.pnas.org/content/112/2/354.full “Cohort of birth modifies the association between FTO genotype and BMI”

Why do researchers title their study the cortex vs. the limbic system or lower brain?

gettingwell4 2-3 stars Required further work, Brain development, Brainstem, Cerebrum, Limbic system, Lower brain, Stress ,

This 2012 review of 89 studies was ostensibly of the prefrontal cortex. The review title showed how researchers characterize their work as studying the cerebrum, even when they primarily deal with the limbic system and lower brains.

For example, the reviewer discussed rodent studies of the developing pup fetus regarding:

  • Sensory/motor – Paternal complex housing, maternal complex housing
  • Stress – Mild stress, bystander stress, moderate stress
  • Psychoactive drugs – Stimulants
  • Adult stimulants – Ethanol

The active brain areas of the rodent fetus are the brainstem and the limbic system, and those areas were primarily what was studied. The cerebrum of the developing pup is a tiny strip that has little cognitive function.

http://www.pnas.org/content/109/Supplement_2/17186.full “Experience and the developing prefrontal cortex”

Maternal depression and antidepressants epigenetically change infant language development

gettingwell4 4-5 stars Advanced knowledge, Brain development, Epigenetics, Neurochemicals, Serotonin , , , , ,

This 2012 human study found that infant language development accelerated when the depressed mother-to-be took antidepressants:

“Language acquisition reflects a complex interplay between biology and early experience.

Psychotropic medication exposure has been shown to alter neural plasticity and shift sensitive periods in perceptual development.”

Infant language development was delayed when the depressed mother-to-be didn’t take serotonin reuptake inhibitor medication:

“Prenatal depressed maternal mood and (S)SRI exposure were found to shift developmental milestones bidirectionally on infant speech perception tasks.”

Contrast this study with Problematic research with telomere length, which pretended that maternal depression had negligible epigenetic effects on the developing fetus, infant, and child.

http://www.pnas.org/content/109/Supplement_2/17221.full “Prenatal exposure to antidepressants and depressed maternal mood alter trajectory of infant speech perception”

Early human brain development can be greatly modified by environmental factors

gettingwell4 4-5 stars Advanced knowledge, Brain development, Brain hemispheres, Epigenetics , , ,

This 2014 Brazilian human study found that the brains of people born without the corpus callosum, the major connection between brain hemispheres, adapted to this loss:

“The authors believe that the development of alternative pathways results from the brain’s ability for long-distance plasticity and occurs in the utero during embryo development, which indicates that connections formed in the human brain early in development can be greatly modified, and most likely by environmental or genetic factors.”

BRAVO! MORE STUDIES LIKE THIS ONE!

People have limited capability to adapt later in life to corpus callosum injuries or to brain hemisphere disconnection.

http://www.pnas.org/content/111/21/7843.full “Structural and functional brain rewiring clarifies preserved interhemispheric transfer in humans born without the corpus callosum”

Let’s not miss a big clue! Embryonic precursor transplants in adult hippocampus

gettingwell4 0-1 star Wasted resources, Brain development, Hippocampus, Limbic system ,

This 2014 rodent study induced “multiple psychosis-relevant phenotypes“ by disrupting specific functions of the hippocampus. The researchers then “cured” the brain disorders:

“Transplanting interneuron progenitors derived from the embryonic medial ganglionic eminence into adult hippocampus mitigates these abnormalities.”

However, full function of the hippocampus wasn’t restored.

I disagree that this study’s findings:

“Support a rationale for targeting limbic cortical interneuron function in the prevention and treatment of schizophrenia.”

People with schizophrenia aren’t lab rats and shouldn’t be treated as such. They often don’t need something externally done to them to recover from brain disorders.

Doesn’t the fact that embryonic precursors to the adult brain helped “cure” the abnormalities tell us where to look for the disorders’ beginnings? Let’s not miss a big clue as to when brain disorders may start.

http://www.pnas.org/content/111/20/7450.full “Interneuron precursor transplants in adult hippocampus reverse psychosis-relevant features in a mouse model of hippocampal disinhibition”

Similarity in form and function of the hippocampus in rodents, monkeys, and humans

gettingwell4 2-3 stars Required further work, Brain development, Hippocampus, Limbic system, Stress , ,

This 2013 study had something for the anti-evolutionists to chew on.

Is it anti-evolutionary for human brain and behavior researchers to not be informed by animal studies such as those that show prenatal hippocampal damage done to the fetus by the mother’s environment?

http://www.pnas.org/content/110/Supplement_2/10365.full “Similarity in form and function of the hippocampus in rodents, monkeys, and humans”

Problematic research on human brain development

gettingwell4 < 0 Detracted from science, Brain development, Cerebrum, Limbic system , ,

This 2013 UK human study provided details of the growths of infants’ cerebral and limbic system structures. With 55 of the 65 infants in the study born prematurely, the UK researchers found:

“Rapidly developing cortical microstructure is vulnerable to the effects of premature birth, suggesting a mechanism for the adverse effects of preterm delivery on cognitive function.”

The infants’ first set of measurements were taken from 27 to 46 weeks after birth. Follow-up measurements were taken when the infants were two years old.

Only the politically-correct adverse effects on brain development were included in the study, which led to the researchers making only politically-correct findings. Is this what we want from publicly funded scientific research?

  • Although 40 of the 65 infants experienced Caesarian deliveries, no attempt was made by the researchers to study any effects on brain development of their delivery method, an omission presumably due to the political incorrectness of suggesting any adverse effects to non-vaginal deliveries.
  • Similarly disregarded for analysis were the effects on brain development in 14 infants of preeclampsia, a serious complication of pregnancy associated with the development of high blood pressure and protein in the urine.
  • Also disregarded for analysis were the effects on brain development in 13 infants of chorioamnionitis, a condition in pregnant women in which the membranes that surround the fetus and the amniotic fluid are infected by bacteria.

Further, was this all we should expect from the peer review process? The data was presumably there for the reviewers to go back to the researchers and suggest analysis of something other than the predetermined agenda.

http://www.pnas.org/content/110/23/9541.full “Development of cortical microstructure in the preterm human brain”