Month: February 2015

Chronic stress changes the architecture of the hippocampus, leading to depression and cognitive impairment

gettingwell4 4-5 stars Advanced knowledge, Brain development, Cortisol, Epigenetics, Hippocampus, Limbic system, Memory, Neurochemicals, Stress ,

This 2014 rodent study gave further details that:

“Chronic stress, which can precipitate depression, induces changes in the architecture and plasticity of apical dendrites that are particularly evident in the CA3 region of the hippocampus.”

Other studies on the hippocampus CA3 region include:

http://www.pnas.org/content/111/45/16130.full “Role for NUP62 depletion and PYK2 redistribution in dendritic retraction resulting from chronic stress”

The same brain areas are used for spontaneous and rehearsed speech

gettingwell4 4-5 stars Advanced knowledge, Brain hemispheres, Primal Therapy

This 2014 human study found:

“..(brain) areas that respond reliably during spontaneous and rehearsed speech production of the same real-world story are the same.”

This finding highlighted the difficulty a therapist or researcher may encounter in objectively determining another person’s reality.

If the listener relied solely on words and speech, they may not be able to tell whether what’s heard was a planned narrative or if the speech had some other origin. That’s why in Dr. Arthur Janov’s Primal Therapy, for example, the therapist is trained to look beyond the patient’s words to ascertain the feeling being expressed.

Also:

“Production of a real-life narrative is not localized to the left hemisphere but recruits an extensive bilateral network.”

http://www.pnas.org/content/111/43/E4687.full “Coupled neural systems underlie the production and comprehension of naturalistic narrative speech”

Non-PC alert: Treating the mother’s obesity symptoms positively affects the post-surgery offspring

gettingwell4 4-5 stars Advanced knowledge, Epigenetics , ,

This 2013 Quebec human epigenetic study found that DNA methylation – chemical modification that causes genes to express differently – as durably detectable between siblings born before and after their mother’s gastric bypass surgery.

The younger, post-maternal-surgery siblings were found to have DNA indicating reduced risks of developing diabetes and heart disease when compared with the DNA of their older, pre-maternal-surgery siblings. The mothers’ average weight loss was 103 lbs.

It was notable to see this famous research reference cited:

“Prenatal exposure to famine during the Dutch hunger winter of 1944 is associated with obesity with less DNA methylation (“undermethylation”) of the imprinted insulin-like growth factor 2 (IGF2) gene in exposed offspring relative to their unexposed siblings.”

It was also notable to see the reactions to this non-politically-correct finding. For one example, this news article was in full-fledged denial, stating:

“Nor do investigators know whether a father’s weight loss might have a similar impact. It’s also possible that epigenetic inheritance wasn’t at play.”

Other news coverage expressed the memes that:

  • Pregnant women can abuse anything and everything with impunity without any consequent damage to their fetus, and
  • There wasn’t the tiniest chance that the mother was involved in any of their child’s adverse outcomes. When the child’s diverted developmental and behavioral consequences manifested, political correctness would dictate that these arose out of some unknown factors.

http://www.pnas.org/content/110/28/11439.full “Differential methylation in glucoregulatory genes of offspring born before vs. after maternal gastrointestinal bypass surgery”

Improvements in tracking and predicting single cell epigenetic changes during embryonic development

gettingwell4 2-3 stars Required further work, Brain development, Epigenetics, Immune system

This 2014 Harvard rodent study demonstrated improvements in tracking and predicting how, during embryonic development, a cell’s environment epigenetically changed the cell’s genetic expression. The researchers stated applicability to human B-cell development in the immune system.

http://www.pnas.org/content/111/52/E5643.full “Bifurcation analysis of single-cell gene expression data reveals epigenetic landscape”

Treating the father’s symptoms of an inherited disease can epigenetically treat the son

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

This 2014 La Jolla rodent study showed that treating the symptoms of an inherited disease can, through epigenetic DNA methylation, positively treat the symptoms in the subjects’ offspring.

The disease studied was Huntington’s, which is the most common inherited neurodegenerative disease:

  • The treatment induced epigenetic changes in the expression of genes on the male Y chromosome.
  • The treated male subjects were bred, and their sperm carried both the Huntington’s disease and the epigenetic changes that reduced the symptoms.
  • The male offspring showed both delayed onsets of Huntington’s disease and reductions of specific symptoms when compared with both the treated subjects’ female offspring and the control group non-treated subjects’ male offspring.

Per the definitions in A review of epigenetic transgenerational inheritance of reproductive disease and Transgenerational effects of early environmental insults on aging and disease, for the term in the study’s title “transgenerational effects” to apply, the researchers needed to provide evidence in at least the next 2 male and/or 3 female generations of:

“Altered epigenetic information between generations in the absence of continued environmental exposure.”

The study instead provided evidence for intergenerational effects.

http://www.pnas.org/content/112/1/E56.full “HDAC inhibition imparts beneficial transgenerational effects in Huntington’s disease mice via altered DNA and histone methylation”

Activation of brainstem neurons induces REM sleep

gettingwell4 4-5 stars Advanced knowledge, Acetylcholine, Brainstem, Lower brain, Neurochemicals

This 2014 MIT/Harvard rodent study provided evidence that specific brainstem neurons (cholinergic, or containing acetylcholine) regulated dream sleep.

The researchers used a more exact technique that selectively activated just one neuron. They made the neurons in this study sensitive to light using an algae protein that responded to a specific light frequency. Once expressed in the neuron, the protein activated the neuron when that specific frequency of light was shown onto it.

“Interestingly, both manipulations resulted in a change in the number of REM [rapid eye movement] sleep episodes and did not change REM sleep episode duration, suggesting that the PPT [pedunculopontine tegmentumis part of the brainstem] involved in REM sleep initiation but not REM sleep maintenance.”

http://www.pnas.org/content/112/2/584.full “Optogenetic activation of cholinergic neurons in the PPT or LDT induces REM sleep”

The brainstem nucleus locus coeruleus is the primary source of norepinephrine

gettingwell4 4-5 stars Advanced knowledge, Brainstem, Cerebrum, Cortisol, Locus coeruleus, Lower brain, Neurochemicals

This 2014 rodent study provided further information on the locus coeruleus segment of the brainstem:

“The brainstem nucleus locus coeruleus is the primary source of norepinephrine to the mammalian neocortex.

Neurons in the locus coeruleus maintain segregated connections to brain regions with distinctly different functions. Specifically, cells that communicate with the prefrontal cortex, a region involved in cognition and executive function, are characterized by properties that allow for independent and asynchronous modulation of operations in this area, compared with those that project to the motor cortex and regulate movement generation.”

http://www.pnas.org/content/111/18/6816.full “Heterogeneous organization of the locus coeruleus projections to prefrontal and motor cortices”

Problematic research: Is sleep deprivation a therapy for depression? Seriously?

gettingwell4 0-1 star Wasted resources, Limbic system

This 2013 Zurich study provided details of depression symptoms, particularly in limbic system structures.

As often happens when researchers are absorbed in studying symptoms, there was nothing about treating the causes, in this case, of depression.

Sleep deprivation as a viable therapy for enduring depression? Is that or drugs really all that science has to offer for depression?

http://www.pnas.org/content/110/48/19597.full “Sleep deprivation increases dorsal nexus connectivity to the dorsolateral prefrontal cortex in humans”

The thalamus’ role in coordinating REM sleep stages

gettingwell4 2-3 stars Required further work, Brainstem, Limbic system, Lower brain, Memory, Thalamus

This 2013 human study provided more details about dream sleep. The thalamus portion of the limbic system coordinates REM stages, which play critical roles in learning and memory.

This study also noted that science assigns no functions to dreams themselves, which was the first I’d heard of it.

http://www.pnas.org/content/110/25/10300.full “Rhythmic alternating patterns of brain activity distinguish rapid eye movement sleep from other states of consciousness”

Problematic research: Feigning naivety of the impact of prenatal, infancy and early childhood experiences

gettingwell4 < 0 Detracted from science, Brain development, Epigenetics, Hippocampus, Limbic system, Memory, Stress

What I found curious in this 2012 UK review of 82 studies was the reviewer’s reluctance to highly regard a human’s life before birth, during infancy, and in early childhood.

There was no lack in 2012 of animal studies to draw from to inferentially hypothesize how a human fetal environment causes the fetus to adapt with enduring epigenetic changes.

To take just one study that I won’t curate on this blog because it’s too old:

Weinstock M (2008) The long-term behavioural consequences of prenatal stress. Neurosci Biobehav Rev 32:1073–1086, “Stress, [to the pregnant mother] in rodents as well as nonhuman primates, produces behavioral abnormalities [in the pup], such as

  • an elevated and prolonged stress response,
  • impaired learning and memory,
  • deficits in attention,
  • altered exploratory behavior,
  • altered social and play behavior, and
  • an increased preference for alcohol.”

Yet the reviewer posed the question:

“There is a need to determine just what epigenetic changes do and do not account for. Put succinctly, do they explain individual differences in response to adversity and do they account for variations in health and behavior outcomes?”

I suspect that the cause of this feigned naivety was the political incorrectness of adequately placing importance in the human fetus’ experience of the development environment provided by their mother.

The PC view would have us pretend that there aren’t lasting adverse effects from human prenatal, infancy, and early childhood experiences.

The follow-on pretense to this PC view would be that later-life consequences aren’t effects, but are instead, mysteries due to “individual differences.”

http://www.pnas.org/content/109/Supplement_2/17149.full “Achievements and challenges in the biology of environmental effects”

This post has somehow become a target for spammers, and I’ve disabled comments. Readers can comment on other posts and indicate that they want their comment to apply here, and I’ll re-enable comments.

Stress impairs the normal matching of neuronal activity to increased blood flow in the amygdala

gettingwell4 4-5 stars Advanced knowledge, Amygdala, Cortisol, Limbic system, Neurochemicals, Stress

This 2014 rodent study showed one aspect of how stress changed the amygdala. Stress didn’t allow normal matching of neuronal activity to increased blood flow:

“Chronic stress — which is a contributing factor for many diseases — impairs neurovascular coupling in the amygdala..

Neurovascular coupling (is) the process that matches neuronal activity with increased local blood flow.”

http://www.pnas.org/content/111/20/7462.full “Stress-induced glucocorticoid signaling remodels neurovascular coupling through impairment of cerebrovascular inwardly rectifying K+ channel function”

Thalamus gating and control of the limbic system and cerebrum is a form of memory

gettingwell4 5+ stars Premium, Cerebrum, Hippocampus, Hypothalamus, Limbic system, Memory, Thalamus ,

This 2014 German rodent study showed how the thalamus actively controlled and gated information to and from the cerebrum.

The researchers elaborated in news coverage on how thalamic control and gating represented a form of memory:

“Q. When asked if, given that

  1. Sensory signals en route to the cortex undergo profound signal transformations in the thalamus,
  2. A key thalamic transformation is sensory adaptation in which neural output adjusts to statistics and dynamics of past stimuli, and
  3. The thalamus, hypothalamus and hippocampus being part of the limbic system, might memory reconsolidation play a role in the cortico-thalamic pathway?

A. “It’s conceivable that the cortico-thalamic pathway is subject to long term plasticity,” Groh conjectures. “In fact, on a synaptic level, these inputs can change their strength and retain adjusted strengths for long periods. This process represents another – albeit much slower – form of adaptation which some interpret as memory.”

Q. Conversely, might the thalamic-cortical pathway affect memory?

A. “If particular sensory-evoked activity patterns would cause long-term changes in the cortico-thalamic pathway, and thereby change the way incoming signals are processed before reaching the cortex,” he opines, “then this would indeed reflect a form of information storage.”

In other words, there are ways in addition to our usual ideas about memory that the limbic system remembers.

Other items in news coverage included:

“Rodents, cats, primates and humans show a common architecture of two feedback pathways from cortex to thalamus in the auditory, visual and somatosensory (but not olfactory) systems.

In this study we looked at processing of touch information, and we’d like to know how homologous pathways affect visual or auditory processing. It’s fascinating that despite fundamental differences between visual, auditory and somatosensory signals, basic layouts of thalamocortical systems for each modality are quite similar.”

Other areas of research that might benefit from their study include any medical research involving the thalamocortical system that might involve inappropriate gating of sensory signals.

For a given stimulus, output neural response will not be static, but will depend on recent stimulus and response history.”

http://www.pnas.org/content/111/18/6798.full “Cortical control of adaptation and sensory relay mode in the thalamus”

Active areas of the brain when making decisions in stressful conditions

gettingwell4 2-3 stars Required further work, Cerebrum, Cortisol, Limbic system, Lower brain, Memory, Neurochemicals, Stress

This 2013 human study was of decision making under stressful conditions.

Acute stress (ice water immersion) evoked habitual behavior rather than deliberative behavior. In my view, the subjects’ behaviors when under stress were driven more by their limbic system and lower brain areas than their cerebrum.

This finding wasn’t a big surprise. However, the researchers went on to state:

“Subjects with more executive resources to spare find themselves less susceptible to the behavioral changes brought about by stress response.”

I interpreted this statement to mean that when stressed, the more-capable subjects didn’t act out as much as the less-capable subjects acted out their respective feelings, instincts and impulses.

I felt that to understand this statement called for more investigation into the individual histories of the subjects:

  • What happened in their lives that enabled each person to acquire “more executive resources” or not?
  • What happened in their lives that made each person more or less sensitive to stress?
  • How are these two avenues of investigation related?

http://www.pnas.org/content/110/52/20941.full “Working-memory capacity protects model-based learning from stress”

How oxytocin and vasopressin were repurposed through evolution to serve social functions

gettingwell4 4-5 stars Advanced knowledge, Neurochemicals, Oxytocin, Vasopressin

This 2013 primate summary study showed how nonsocial behaviors, neurology and neurochemicals were repurposed through evolution to serve social functions.

Oxytocin and vasopressin retained their:

  • water regulation,
  • reproduction, and
  • anxiety relief

functionalities while they also evolved to become instrumental in:

  • pair-bonding,
  • parental care,
  • selective aggression,
  • social prominence,
  • generosity, and
  • trust.

http://www.pnas.org/content/110/Supplement_2/10387.full “Neuroethology of primate social behavior”

A mother’s care affects the infant’s hippocampus structure and function through epigenetic regulation of genes

gettingwell4 4-5 stars Advanced knowledge, Brain development, Epigenetics, Glutamate, Hippocampus, Limbic system, Memory, Neurochemicals, Stress

This 2012 McGill University rodent study found:

“Variations in maternal care in the rat affect hippocampal morphology and function as well as performance on hippocampal-dependent tests of learning and memory in the offspring.

Thus, in the rat, as in humans, social influences operate during early life to influence the structure and function of brain regions critical for cognitive capacity.

Variations in maternal care can influence hippocampal function and cognitive performance through the epigenetic regulation of genes.”

http://www.pnas.org/content/109/Supplement_2/17200.full “Variations in postnatal maternal care and the epigenetic regulation of metabotropic glutamate receptor 1 expression and hippocampal function in the rat”