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.)

Narcissism Not in DSM-V

Narcissistic personality disorder, characterized by an inflated sense of self-importance and the need for constant attention, has been eliminated from the upcoming manual of mental disorders, which psychiatrists use to diagnose mental illness.

As Charles Zanor reports in today’s Science Times, the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders — due out in 2013 and known as D.S.M.-5 — has eliminated five of the 10 personality disorders that are listed in the current edition. (via.)

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.)

Bacteria playing their part in autism, diagnostic opportunity

“Gut bacteria may contribute to autism”

Children with autism appear to have a characteristic chemical signature in their urine which might form the basis of an early diagnostic test for the condition.

The finding also adds weight the hypothesis that substances released by gut bacteria are contributing to the onset of the condition.

Autism has previously been linked to metabolic abnormalities and gastrointestinal problems such as gut pain and diarrhoea. Several studies have also hinted at changes in gut bacteria in the faeces of children with autism. [...]

Using nuclear magnetic resonance (NMR) spectroscopy to analyse the children’s urine, they found that each of these groups had a distinct chemical fingerprint, with clear and significant differences between children with autism and unrelated controls.”The signature that comes up is related to gut bacteria,” says Nicholson. It is not yet clear whether the bacteria’s metabolic products contribute to the development of autism, but it is a possibility worth investigating, he adds. A large proportion of autistic children have severe gastrointestinal problems that tend to appear at about the same time as the behavioural symptoms.

“It adds another link to the gut bacterial involvement in the onset of disorder,” says Glenn Gibson of the University of Reading, UK, who has previously identified abnormally high levels of clostridium bacteria in children with autism.

One possibility is that the gut bacteria in children with autism are producing toxins that might interfere with brain development. One of the compounds identified in the urine of autistic children was N-methyl-nicotinamide (NMND), which has also been implicated in Parkinson’s disease.

Meanwhile, Derrick MacFabe of the University of Western Ontario in London, Canada, and his colleagues have found that short-chain fatty acids produced by clostridium bacteria can induce reversible autism-like behavioural and biochemical changes in rats. [...]

Even if bacteria are not actually contributing to the observed metabolic changes, they could still be put to use. “There is probably the basis of a test for autism based on a urinary metabolic profile,” says Nicholson. (via: 1,2.)

Shouts out to Dale for sharing this interesting link with me.

East & Western Cultural Values: Honesty, Dominance & Submission

When an American thinks about whether he is honest, his brain activity looks very different than when he thinks about whether another person is honest, even a close relative. That’s not true for Chinese people. When a Chinese man evaluates whether he is honest, his brain activity looks almost identical to when he is thinking about whether his mother is honest.

That finding — that American and Chinese brains function differently when considering traits of themselves versus traits of others (Neuroimage, Vol. 34, No. 3) — supports behavioral studies that have found that people from collectivist cultures, such as China, think of themselves as deeply connected to other people in their lives, while Americans adhere to a strong sense of individuality.

Different study, but from the same article:

Ambady’s group based the study on historical data showing that East-Asian cultures value submissiveness, while Western cultures value dominance. In fact, they found, they could see this cultural distinction in the way the brain responds to visual input. When Americans viewed dominant silhouettes, but not submissive ones, reward circuitry fired in the brain’s limbic system. The opposite happened among Japanese participants; their reward circuitry fired in response to submissive, but not dominant, silhouettes.

… same article:

Most recently, a study by Park’s group, in press in Social Cognitive and Affective Neuroscience demonstrated that Westerners process human faces more actively than East Asians, consistent with the Western focus on individuality.

… last interesting tidbit:

The researchers sought to find a biological explanation for past research showing that people from collectivist cultures relate more strongly to contextual self-descriptions, such as “When I’m with my mother, I’m honest.” People from already defined individualistic cultures relate more strongly to general self-descriptions such as “I’m honest.”

When Chiao and her colleagues compared participants along ethnic lines, they saw no difference in brain activity. Differences appeared only after they grouped people based on how strongly they valued collectivism or individualism: Regardless of ethnicity, the medial prefrontal cortex was most active when individualists read general self-descriptions and when collectivists read contextual self-descriptions.


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.

Fewer 5HT2a (serotonin) receptors in pcc & acc in autistics

The posterior cingulate cortex (PCC) is activated when normal subjects see faces or hear voices of emotionally significant people in their lives; however, in autism the level of activation is impaired. [...]

The use of selective serotonin reuptake inhibitor (SSRI) medication has been shown to be successful in the treatment of autistic behaviors in some individuals. Serotonin (5-HT) has a role in neuronal development and has been extensively studied in autism with reports of excess 5-HT in the blood (hyperserotonemia) in some people with autism. [...]

The results show that there was a significant decrease in the density of one key type of serotonin receptor, the 5HT2A receptor, in the superficial cortical layers of the PCC in the adult autistic group when compared to age-matched controls. Similar results were found recently in the anterior cingulate cortex, an area involved in social-emotional processing. Evaluated together, these findings suggest that the 5-HT2a serotonin receptor decrease occurs in widespread cortical areas and may play a central role in some of the social deficits observed in autism. (via.)

Epilepsy & hyperthermia in rats

Many mild preconditioning stress conditions, including physical and metabolic injuries, increase the resistance of neurons to subsequent more severe stresses of the same or different type. This “tolerance phenomenon” lasts one to several weeks, providing a unique opportunity to investigate endogenous neuroprotective mechanisms. The aim of this study was to find a physiological and easily applicable preconditioning stimulus able to confer protection against convulsant-induced neuronal damage and seizures. We found that moderate transient hyperthermic preconditioning markedly reduced kainic-acid-induced neuronal cell loss and attenuated susceptibility to bicuculline-induced seizures. Prevention of cell damage (approximately 50%) was efficient both in vitro in organotypic hippocampal slice cultures and in vivo in adult rats. This protection lasted about 1 week and peaked 3 to 5 days after pretreatment. Unraveling the mechanisms of heat shock preconditioning-induced protection against epilepsy should lead to the development of new therapeutic strategies. (via.)

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.)

Prophet Ezekiel & Temporal Lobe Epilepsy

After watching Robert Sapolsky’s video on religion I decided to do some reading up on temporal lobe epilepsy and hypergraphia… I ran across this:

THE Bible may contain the oldest recorded case of temporal lobe epilepsy. Ezekiel, the prophet whose visions are recorded in a book of the Old Testament, apparently had all the classic signs of the condition. [...]

People with the disease experience partial seizures, often accompanied by a dreamy feeling that things are not quite as they should be. Patients are often misdiagnosed with psychiatric problems. Neurologically, Ezekiel displayed some obvious signs of epilepsy, such as frequent fainting spells and episodes of not being able to speak.

The Biblical figure, who chronicled the fall of Jerusalem in 586 BC, exhibited other peculiarities associated with the disease. For instance, he wrote compulsively, a trait known as hypergraphia. Altschuler points out that the Book of Ezekiel is the fourth longest in the Bible-only slightly shorter than Genesis. “It’s impenetrable,” he says. “He goes on and on.”

Ezekiel was also extremely religious, another characteristic associated with this form of epilepsy. While many Biblical figures are pious, none was as aggressively religious as Ezekiel, says Altschuler. (via.)