Modulation of brain-derived neurotrophic factor (BDNF)
Described is a low voltage, pulsed electrical stimulation device for controlling expression of Brain-Derived Neurotrophic Factor (“BDNF”), a useful protein, by tissues. Also described are methods of enhancing expression of BDNF in cells, particularly a method of stimulating the expression and/or release of BDNF in a cell having a gene encoding BDNF, wherein the method includes applying a bioelectric signal of from about 10 Hz to about 100 Hz (e.g., 5 Hz, 10 Hz, 40 Hz, 100 Hz, or 110 Hz) to the cell (e.g., directly, indirectly, or wirelessly). Applications in the treatment of Alzheimer's disease, depression, schizophrenia, and post-traumatic stress disorder are also disclosed.
1 . A method of treating a subject for Alzheimer's disease, schizophrenia, post-traumatic stress disorder, addiction(s), and/or depression using a bioelectric stimulator comprising an electric signal generator and electrode(s), which electric signal generator is programmed to produce at least one bioelectric signal that stimulates target tissue comprising living cells of the subject to upregulate expression and/or release of brain-derived neurotrophic factor (BDNF) by the living cells, wherein the bioelectric signal comprises, within 15%, a bioelectric signal having a biphasic pulse at a frequency selected from the group consisting of 1 Hz, 10 Hz, 40 Hz, 80 Hz, and 100 Hz, with a pulse width of either about 300 microseconds or about 1,000 microseconds, and a current of about 2 mA as may be measured at the cellular level to stimulate target tissue comprising the living cells of the subject, the method comprising:
administering the bioelectric signal to the living cells via the electrode(s) for at least 5 minutes to about an hour, so as to upregulate the expression of BDNF by the living cells so as to treat the subject for Alzheimer's disease, schizophrenia, post-traumatic stress disorder, addiction(s), and/or depression.
2 . The method according to claim 1 , wherein the bioelectric signal has, within 15%, a biphasic pulse at a frequency selected from the group consisting of 1 Hz, 10 Hz, 40 Hz, 80 Hz, and 100 Hz, which bioelectric signal upregulates expression of BDNF by the living cells of the target tissue.
3 . The method according to claim 2 , wherein the bioelectric signal has a frequency of about 1 Hz.
4 . The method according to claim 2 , wherein the bioelectric signal has a frequency of about 40 Hz.
5 . The method according to claim 2 , wherein the bioelectric signal has a frequency of about 80 Hz.
6 . The method according to claim 2 , wherein the bioelectric signal has a frequency of about 100 Hz.
7 . The method according to claim 1 , wherein the target tissue comprises gray matter of the neocortex.
8 . The method according to claim 1 , wherein the bioelectric signal is administered for about 60 minutes.
9 . The method according to claim 1 , wherein the bioelectric signal comprises about 10 Hz and about 300 microseconds pulse width.
10 . The method according to claim 1 , wherein the upregulation of BDNF expression comprises at least a 2-fold increase in BDNF expression relative to an unstimulated control.
11 . The method according to claim 1 , wherein upregulation of BDNF is determined by analysis of mRNA expression normalized to a housekeeping gene.
12 . The method according to claim 1 , wherein the bioelectric stimulator is external to the subject.
13 . The method according to claim 1 , wherein the bioelectric signal is delivered wirelessly to the target tissue.
14 . The method according to claim 1 , further comprising administering stem cells to the subject.