Brain-Derived Neurotrophic Factor & Serotonin Effects on Aging, Plasticity & More


BDNF and 5-HT: a dynamic duo in
age-related neuronal plasticity and
neurodegenerative disorders

Brain-derived neurotrophic factor (BDNF) and serotonin (5-hydroxytryptamine, 5-HT) are known to regulate synaptic plasticity, neurogenesis and neuronal survival in the adult brain. These two signals co-regulate one another such that 5-HT stimulates the expression of BDNF, and BDNF enhances the growth and survival of 5-HT neurons. Impaired 5-HT and BDNF signaling is central to depression and anxiety disorders, but could
also play important roles in the pathogenesis of several age-related disorders, including insulin resistance syndrome, Alzheimer’s disease and Huntington’s disease.
Enhancement of BDNF signaling may be a key mechanism whereby cognitive stimulation, exercise, dietary restriction and antidepressant drugs preserve brain function during aging. Behavioral and pharmacological manipulations that enhance 5-HT and BDNF signaling
could help promote healthy brain aging. [...]

By promoting neurogenesis,
synaptic plasticity and cell survival, BDNF plays a pivotal
role in the development and plasticity of the brain. During
development of the cerebral cortex and hippocampus,
BDNF induces the differentiation of neural stem cells into
neurons and promotes the survival of newly generated
neurons [1–3]. BDNF signaling at synapses enhances
long-term potentiation (LTP), a process of synaptic
strengthening associated with learning and memory;
the effect of BDNF on LTP is apparently mediated by
cAMP-response-element-binding protein (CREB), which
regulates the expression of genes involved in LTP and
memory formation [4]. Levels of BDNF are increased in
the hippocampus of rats during and after performance
of a spatial learning task (a radial-arm maze), and both
acquisition and maintenance of spatial memory are
impaired when BDNF levels are decreased using antisense
methods [5]. In rats that had previously acquired
spatial memory by extensive training, suppression of
BDNF expression impaired both reference and working
memory [5]. Another study showed that mice lacking one
copy of the BDNF gene exhibit impaired spatial learning
in the Morris water maze [6]. BDNF also plays an important
role in preventing death of neurons during development,
and promotes cell survival during stressful conditions
such as ischemia and trauma in the adult brain [7]. [...]

[A]ctivation of 5-HT1A receptors can impair learning and
memory whereas 5-HT2A and 5-HT2C receptors facilitate
memory formation [10]. [...]

5-HT can
also promote the survival of neurons in the adult brain, as
demonstrated by the abilities of a 5-HT receptor agonist
and SSRI to protect neurons against excitotoxic and
ischemic injury in animal models [12,13]. There are therefore
several commonalities of function in the CNS for
BDNF and 5-HT in terms of their effects on synaptic
plasticity, neurogenesis and cell survival. [...]

Conversely, BDNF
can stimulate the growth and sprouting of 5-HT neuron
axons innervating the cerebral cortex, thereby presumably
increasing the number of 5-HT synapses in this brain
region [14]. (via: pdf.)


Anabolic steroids, depression, BDNF & morning corticosterone levels


Abuse of anabolic androgenic steroids (AASs) is frequently associated with changes in mood, including depression. [...] We used male adult rats injected for 4 weeks with either nandrolone or stanozolol at daily doses (5 mg/kg, s.c.) that are considered equivalent to those abused by humans [...] AAS treatment reduced levels of brain-derived neurotrophic factor in the hippocampus and prefrontal cortex, reduced the expression of low-affinity glucocorticoid receptors in the hippocampus, and increased morning trough basal plasma corticosterone levels. All these changes have been related to the pathophysiology of major depressive disorder. Accordingly, rats treated with nandrolone or stanozolol showed an increased immobility time in the forced swim test, which is widely used for the screening of antidepressant drugs. All effects produced by AASs were prevented by co-administration with the classical antidepressant, chlorimipramine. (via.)


Increased serum levels of BDNF, reduced cerebellum levels in Autism


There is compelling evidence that led to the hypothesis of a role of BDNF in the development of autism including increased serum concentrations of BDNF in children with autism and identification of different forms of BDNF in families of autistic individuals. [...]

In this study the regulation of BDNF in the cerebellum of six autistic patients and six controls was studied by measuring the protein level of BDNF in post mortem tissues. The level of BDNF was significantly decreased in the autistic group compared to controls. Reduced BDNF in the cerebellum may be an indicator of aberrant brain development and growth in autism. (via.)

Additionally, the same page that quote came from had this little interesting tidbit about serotonin and autism.


BDNF, hyperlexia, hypergraphia, seizures…


Just some loosely connected neuro-things I wanted to save somewhere.

  • Notably without citation, Wikipedia claims BDNF is also expressed in the retina, the central nervous system, motor neurons, the kidneys, and the prostate (aside from just the hippocampus and cerebral cortex). (via.)
  • BDNF knockingout in mice affects coordination, balance, hearing, taste, and breathing. “Knockout mice also exhibit cerebellar abnormalities and an increase in the number of sympathetic neurons.” (via.)
  • BDNF is increased by prolonged seizures, and important to GABA pathways. (via.)
  • Hypergraphia, a condition which afflicts individuals with a compulsive desire to write, is associated with temporal lobe epilepsy… and quite a few interesting characters have had it. (via.)
  • Hyperlexia, the extreme variety of a compulsion to read, may be caused by a “cerebral infarction in the left anterior cingulate cortex and corpus callosum.” (via.)
  • Temporal lobe epileptics are often hyposexual. (via.)

Exercise reverses anxiety phenotype in rats


Exercise can ameliorate anxiety and depression-like behaviours induced by an adverse early-life environment by altering the chemical composition in the hippocampus – the part of the brain that regulates stress response, researchers from UNSW have found. [...]

“What’s exciting about this is that we are able to reverse a behavioural deficit that was caused by a traumatic event early in life, simply through exercise,” said Professor of Pharmacology Margaret Morris, who will present the findings this week at the International Congress of Obesity in Stockholm.

In the study, rats were divided into groups and either isolated from their mothers for controlled periods of time to induce stress or given normal maternal contact. Half were given access to a running wheel.

In addition to being more anxious, animals that were subjected to stress early in life had higher levels of stress hormones and fewer steroid receptors in the part of the brain controlling behaviour.

“Both the anxious behaviour and the levels of hormones in these rats were reversed with access to the exercise wheel,” Professor Morris said.

“We know that exercise can elevate mood, but here we are seeing chemical changes that may underpin this improvement. One of these is increases in brain-derived neurotrophic factor (BDNF), which helps nerve cells grow. (via.)

In other news…
Morphine found to decrease testosterone in the brain, as well as liver, and testis. Which is interesting in light of the fact that a stressed/anxious phenotype of rat would have fewer steroid receptors in their brain.


What’s BDNF & substance p got to do with eczema?


Per Wikipedia BDNF is…

BDNF acts on certain neurons of the central nervous system and the peripheral nervous system, helping to support the survival of existing neurons, and encourage the growth and differentiation of new neurons and synapses.

So I ran across this little interesting tidbit that I’ll want to follow up on later, if I happen to remember to. That is that apparently elevated levels of BDNF and Substance P (involved in nociception/pain perception) is involved in eczema? Per Substance P’s Wikipedia:

High levels of BDNF and Substance P have been found associated with increased itching in eczema.[27][28]

Interestingly also, apparently naked mole rats lack substance p altogether.

Totally unrelated, but also unusual… BDNF is found to be increased after prolonged seizure activity.