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BDNF -- The True Master Signal?

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Okay, there is not going to be a true one master signal, as the body has a bunch of redundant systems, but BDNF may be the closest thing to it. It is increased by proper leptin and insulin signalling, decreased by cortisol, modulates the the positive neurotransmitter response and neurogenesis from exercise and anti-depressants, and it controls feeding and metabolic behavior....


Behav Neurosci. 2012 Aug;126(4):505-14. doi: 10.1037/a0028600. Epub 2012 Jun 11.

A putative model of overeating and obesity based on brain-derived neurotrophic
factor: direct and indirect effects.

Ooi CL(1), Kennedy JL, Levitan RD.

Author information: 
(1)Department of Psychiatry, University of Toronto, Ontario, Canada.

Increased food intake is a major contributor to the obesity epidemic in all age
groups. Elucidating brain systems that drive overeating and that might serve as
targets for novel prevention and treatment interventions is thus a high priority 
for obesity research. The authors consider 2 major pathways by which decreased
activity of brain-derived neurotrophic factor (BDNF) may confer vulnerability to 
overeating and weight gain in an obesogenic environment. The first "direct"
pathway focuses on the specific role of BDNF as a mediator of food intake control
at brain areas rich in BDNF receptors, including the hypothalamus and hindbrain. 
It is proposed that low BDNF activity limited to this direct pathway may best
explain overeating and obesity outside the context of major neuropsychiatric
disturbance. A second "indirect" pathway considers the broad neurotrophic effects
of BDNF on key monoamine systems that mediate mood dysregulation, impulsivity,
and executive dysfunction as well as feeding behavior per se. Disruption in this 
pathway may best explain overeating and obesity in the context of various
neuropsychiatric disturbances including mood disorders, attention-deficit
disorder, and/or binge eating disorders. An integrative model that considers
these potential roles of BDNF in promoting obesity is presented. The implications
of this model for the early prevention and treatment of obesity are also

DOI: 10.1037/a0028600 
PMID: 22687148  [Indexed for MEDLINE]


Trends Neurosci. 2013 Feb;36(2):83-90. doi: 10.1016/j.tins.2012.12.009. Epub 2013
Jan 18.

BDNF and the central control of feeding: accidental bystander or essential

Rios M(1).

Author information: 
(1)Tufts University School of Medicine, Department of Neuroscience, Boston, MA
02111, USA. maribel.rios@tufts.edu

A considerable body of evidence links diminished brain-derived neurotrophic
factor (BDNF) signaling to energy balance dysregulation and severe obesity in
humans and rodents. Because BDNF exhibits broad neurotrophic properties, the
underpinnings of these effects and its true role in the central regulation of
food intake remain topics of debate in the field. Here, I discuss recent evidence
supporting a critical role for this neurotrophin in physiological mechanisms
regulating nutrient intake and body weight in the mature brain. They include
reports of functional interactions of BDNF with central anorexigenic and
orexigenic signaling pathways and evidence of recognized appetite hormones
exerting neurotrophic effects similar to those of BDNF.

Copyright © 2013 Elsevier Ltd. All rights reserved.

DOI: 10.1016/j.tins.2012.12.009 
PMCID: PMC3568936
PMID: 23333344  [Indexed for MEDLINE]


Psychiatry Clin Neurosci. 2010 Oct;64(5):447-59. doi:

Interface between hypothalamic-pituitary-adrenal axis and brain-derived
neurotrophic factor in depression.

Kunugi H(1), Hori H, Adachi N, Numakawa T.

Author information: 
(1)Department of Mental Disorder Research, National Institute of Neuroscience,
National Center of Neurology and Psychiatry, Tokyo, Japan. hkunugi@ncnp.go.jp

Although the pathophysiology of depressive disorder remains elusive, two
hypothetical frameworks seem to be promising: the involvement of hypothalamic
pituitary-adrenal (HPA) axis abnormalities and brain-derived neurotrophic factor 
(BDNF) in the pathogenesis and in the mechanism of action of antidepressant
treatments. In this review, we focused on research based on these two frameworks 
in relation to depression and related conditions and tried to formulate an
integrated theory of the disorder. Hormonal challenge tests, such as the
dexamethasone/corticotropin-releasing hormone test, have revealed elevated HPA
activity (hypercortisolism) in at least a portion of patients with depression,
although growing evidence has suggested that abnormally low HPA axis
(hypocortisolism) has also been implicated in a variety of stress-related
conditions. Several lines of evidence from postmortem studies, animal studies,
blood levels, and genetic studies have suggested that BDNF is involved in the
pathogenesis of depression and in the mechanism of action of biological
treatments for depression. Considerable evidence has suggested that stress
reduces the expression of BDNF and that antidepressant treatments increase it.
Moreover, the glucocorticoid receptor interacts with the specific receptor of
BDNF, TrkB, and excessive glucocorticoid interferes with BDNF signaling. Altered 
BDNF function is involved in the structural changes and possibly impaired
neurogenesis in the brain of depressed patients. Based on these findings, an
integrated schema of the pathological and recovery processes of depression is

© 2010 The Authors. Psychiatry and Clinical Neurosciences © 2010 Japanese Society
of Psychiatry and Neurology.

DOI: 10.1111/j.1440-1819.2010.02135.x 
PMID: 20923424  [Indexed for MEDLINE]


Med Hypotheses. 2016 May;90:23-8. doi: 10.1016/j.mehy.2016.02.020. Epub 2016 Mar 

FNDC5/irisin, a molecular target for boosting reward-related learning and

Zsuga J(1), Tajti G(2), Papp C(2), Juhasz B(3), Gesztelyi R(4).

Author information: 
(1)Department of Health Systems Management and Quality Management for Health
Care, Faculty of Public Health, University of Debrecen, Nagyerdei krt 98, 4032
Debrecen, Hungary. Electronic address: zsuga.judit@med.unideb.hu.
(2)Department of Health Systems Management and Quality Management for Health
Care, Faculty of Public Health, University of Debrecen, Nagyerdei krt 98, 4032
Debrecen, Hungary.
(3)Department of Pharmacology and Pharmacotherapy, Faculty of Medicine,
University of Debrecen, Nagyerdei krt 98, 4032 Debrecen, Hungary.
(4)Department of Pharmacology, Faculty of Pharmacy, University of Debrecen,
Nagyerdei krt 98, 4032 Debrecen, Hungary.

Interventions focusing on the prevention and treatment of chronic
non-communicable diseases are on rise. In the current article, we propose that
dysfunction of the mesocortico-limbic reward system contributes to the emergence 
of the WHO-identified risk behaviors (tobacco use, unhealthy diet, physical
inactivity and harmful use of alcohol), behaviors that underlie the evolution of 
major non-communicable diseases (e.g. cardiovascular diseases, cancer, diabetes
and chronic respiratory diseases). Given that dopaminergic neurons of the
mesocortico-limbic system are tightly associated with reward-related processes
and motivation, their dysfunction may fundamentally influence behavior. While
nicotine and alcohol alter dopamine neuron function by influencing some
receptors, mesocortico-limbic system dysfunction was associated with elevation of
metabolic set-point leading to hedonic over-eating. Although there is some
empirical evidence, precise molecular mechanism for linking physical inactivity
and mesocortico-limbic dysfunction per se seems to be missing; identification of 
which may contribute to higher success rates for interventions targeting
lifestyle changes pertaining to physical activity. In the current article, we
compile evidence in support of a link between exercise and the mesocortico-limbic
system by elucidating interactions on the axis of muscle - irisin - brain derived
neurotrophic factor (BDNF) - and dopaminergic function of the midbrain. Irisin is
a contraction-regulated myokine formed primarily in skeletal muscle but also in
the brain. Irisin stirred considerable interest, when its ability to induce
browning of white adipose tissue parallel to increasing thermogenesis was
discovered. Furthermore, it may also play a role in the regulation of behavior
given it readily enters the central nervous system, where it induces BDNF
expression in several brain areas linked to reward processing, e.g. the ventral
tegmental area and the hippocampus. BDNF is a neurotropic factor that increases
neuronal dopamine content, modulates dopamine release relevant for neuronal
plasticity and increased neuronal survival as well as learning and memory.
Further linking BDNF to dopaminergic function is BDNF's ability to activate
tropomyosin-related kinase B receptor that shares signalization with presynaptic 
dopamine-3 receptors in the ventral tegmental area. Summarizing, we propose that 
the skeletal muscle derived irisin may be the link between physical activity and 
reward-related processes and motivation. Moreover alteration of this axis may
contribute to sedentary lifestyle and subsequent non-communicable diseases.
Preclinical and clinical experimental models to test this hypothesis are also

Copyright © 2016 Elsevier Ltd. All rights reserved.

DOI: 10.1016/j.mehy.2016.02.020 
PMID: 27063080  [Indexed for MEDLINE]


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