Monday, March 12, 2012

Unconventional Brain Modifications

A team of neuroscientists had discovered a genetic manipulation which provides a long term increase in brain neurogenesis in mice, and which appears to boost learning and reduce anxiety and depression.
...genetic deletion of neurofibromin (Nf1), a tumor suppressor with RAS-GAP activity, in adult NPCs enhanced DG proliferation and increased generation of new neurons in mice. Nf1 loss-associated neurogenesis had the functional effect of enhancing behavioral responses to subchronic antidepressants and, over time, led to spontaneous antidepressive-like behaviors. Thus, our findings establish an important role for the Nf1-Ras pathway in regulating adult hippocampal neurogenesis, and demonstrate that activation of adult NPCs is sufficient to modulate depression- and anxiety-like behaviors. _Journal of Neuroscience
More from ScienceDaily news service:
The researchers found that the test group mice formed more neurons over time compared to controls, and that young mice lacking the Nf1 protein required much lower amounts of anti-depressants to counteract the effects of stress. Behavioral differences between the groups persisted at three months, six months and nine months. "Older mice lacking the protein responded as if they had been taking antidepressants all their lives," said Dr. Parada.

"In summary, this work suggests that activating neural precursor cells could directly improve depression- and anxiety-like behaviors, and it provides a proof-of-principle regarding the feasibility of regulating behavior via direct manipulation of adult neurogenesis," Dr. Parada said. _SD
This type of genetic manipulation will necessarily require further development before it is suitable for use in humans. In particular, it will have to be both reversible, and adjustable in effect.

The increase in hippocampal neurons also suggests the potential for augmenting learning ability in the altered mice over their full lifetimes.

Another interesting brain manipulation studied recently, is the use of the hallucinogenic drug LSD (lysergic acid diethylamide) to aid alcoholics in overcoming their addiction to ethanol. LSD has previously been used effectively to reduce cancer associated pain in terminal cancer patients, as well as to reduce or eliminate the fear of death in terminal cancer patients.

Here is more on a recent meta-analysis of the use of LSD for treating alcohol dependency:
Krebs and Johansen set out to independently extract data from previous randomized, controlled clinical trials, pooling their results. They identified six eligible trials, all carried out in the late 1960s and early 1970s. These included 536 participants, the vast majority of whom were male in-patients enrolled in alcohol-focused treatment programs. Individuals with a history of schizophrenia or psychosis were excluded from the original trials. The control conditions included low-dose LSD, stimulants, or non-drug control conditions. Each trial used clearly defined treatment-independent and standardized methods to assess outcomes on alcohol misuse.

While the experiments varied in the dosage used and the type of placebo physicians administered to patients, LSD had a beneficial effect on alcohol misuse in every trial. On average, 59 percent of LSD patients and 38 percent of control patients were improved at follow-up using standardized assessment of problem alcohol use. There was also a similar beneficial effect on maintained abstinence from alcohol. The positive effects of a single LSD dose -- reported both in these and in other, non-randomized trials -- lasts at least six months and appears to fade by 12 months. _ScienceDaily
Full study in Journal of Psychopharmacology (PDF)

Other hallucinogenic drugs besides LSD which may prove to have beneficial clinical uses include psilocybin, ketamine, and marijuana.

The human brain is an incredibly complex and dynamic organ. We should not be surprised when such a complex device sometimes "malfunctions." And we should maintain relatively open minds when in pursuit of ways to stabilise and improve brain function.

We are playing for very high stakes.



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