The Effect of 40-Hz White LED Therapy on Structure-Function of Brain Mitochondrial ATP-Sensitive Ca-Activated Large-Conductance Potassium Channel in Amyloid Beta Toxicity.

Photobiomodulation therapy has become the focus of medical research in many areas such as Alzheimer's disease (AD), because of its modulatory effect on cellular processes through light energy absorption via photoreceptors/chromophores located in the mitochondria. However, there are still many questions around the underlying mechanisms. This study was carried out to unravel whether the function-structure of ATP-sensitive mitoBKCa channels, as crucial components for maintenance of mitochondrial homeostasis, can be altered subsequent to light therapy in AD. Induction of Aß neurotoxicity in male Wistar rats was done by intracerebroventricular injection of Aß1-42. After a week, light-treated rats were exposed to 40-Hz white light LEDs, 15 min for 7 days. Electrophysiological properties of mitoBKCa channel were investigated using a channel incorporated into the bilayer lipid membrane, and mitoBKCa-ß2 subunit expression was determined using western blot analysis in Aß-induced toxicity and light-treated rats. Our results describe that conductance and open probability (Po) of mitoBKCa channel decreased significantly and was accompanied by a Po curve rightward shift in mitochondrial preparation in Aß-induced toxicity rats. We also showed a significant reduction in expression of mitoBKCa-ß2 subunit, which is partly responsible for a leftward shift in BKCa Po curve in low calcium status. Interestingly, we provided evidence of a significant improvement in channel conductance and Po after light therapy. We also found that light therapy improved mitoBKCa-ß2 subunit expression, increasing it close to saline group. The current study explains a light therapy improvement in brain mitoBKCa channel function in the Aß-induced neurotoxicity rat model, an effect that can be linked to increased expression of ß2 subunit.

The 40-Hz White Light-Emitting Diode (LED) Improves the Structure-Function of the Brain Mitochondrial KATP Channel and Respiratory Chain Activities in Amyloid Beta Toxicity.

It has been described that using noninvasive exposure to 40-Hz white light LED reduces amyloid-beta, a peptide thought to initiate neurotoxic events in Alzheimer's disease (AD). However, the mechanisms remain to be identified. Since AD impairs mitochondrial potassium channels and respiratory chain activity, the objectives of the current study were to determine the effect of 40-Hz white light LED on structure-function of mitoKATP channel and brain mitochondrial respiratory chain activity, production of reactive oxygen species (ROS), and ΔΨm in AD. Single mitoKATP channel was considered using a channel incorporated into the bilayer lipid membrane and expression of mitoKATP-Kir6.1 subunit as a pore-forming subunit of the channel was determined using a western blot analysis in Aß1-42 toxicity and light-treated rats. Our results indicated a severe decrease in mito-KATP channel permeation and Kir6.1 subunit expression coming from the Aß1-42-induced neurotoxicity. Furthermore, we found that Aß1-42-induced neurotoxicity decreased activities of complexes I and IV and increased ROS production and ΔΨm. Surprisingly, light therapy increased channel permeation and mitoKATP-Kir6.1 subunit expression. Noninvasive 40-Hz white light LED treatment also increased activities of complexes I and IV and decreased ROS production and ΔΨm up to ~ 70%. Here, we report that brain mito-KATP channel and respiratory chain are, at least in part, novel targets of 40-Hz white light LED therapy in AD.

Intranasal insulin improves the structure-function of the brain mitochondrial ATP-sensitive Ca2+ activated potassium channel and respiratory chain activities under diabetic conditions.

Although it is well established that diabetes impairs mitochondrial respiratory chain activity, little is known of the effects of intranasal insulin (INI) on the mitochondrial respiratory chain and structure-function of mitoBKCa channel in diabetes. We have investigated this mechanism in an STZ-induced early type 2 diabetic model. Single ATP-sensitive mitoBKCa channel activity was considered in diabetic and INI-treated rats using a channel incorporated into the bilayer lipid membrane. Because mitoBKCa channels have been involved in mitochondrial respiratory chain activity, a study was undertaken to investigate whether the NADH, complexes I and IV, mitochondrial ROS production, and ΔΨm are altered in an early diabetic model. In this work, we provide evidence for a significant decrease in channel open probability and conductance in diabetic rats. Evidence has been shown that BKCa channel ß2 subunits induce a left shift in the BKCa channel voltage dependent curve in low Ca2+ conditions,; our results indicated a significant decrease in mitoBKCa ß2 subunits using Western blot analysis. Importantly, INI treatment improved mitoBKCa channel behaviors and ß2 subunits expression up to ~70%. We found that early diabetes decreased activities of complex I and IV and increased NADH, ROS production, and ΔΨm. Surprisingly, INI modified the mitochondrial respiratory chain, ROS production, and ΔΨm up to ~70%. Our results thus demonstrate an INI improvement in respiratory chain activity and ROS production in brain mitochondrial preparations coming from the STZ early diabetic rat model, an effect potentially linked to INI improvement in mitoBKCa channel activity and channel ß2 subunit expression.

A new brain mitochondrial sodium-sensitive potassium channel: effect of sodium ions on respiratory chain activity.

We have determined the electropharmacological properties of a new potassium channel from brain mitochondrial membrane using a planar lipid bilayer method. Our results show the presence of a channel with a conductance of 150 pS at potentials between 0 and -60 mV in 200 mM cis/50 mM trans KCl solutions. The channel was voltage independent, with an open probability value of approximately 0.6 at different voltages. ATP did not affect current amplitude or open probability at positive and negative voltages. Notably, adding iberiotoxin, charybdotoxin, lidocaine or margatoxin had no effect on the channel behavior. Similarly, no changes were observed by decreasing the cis pH to 6. Interestingly, the channel was inhibited by adding sodium in a dose-dependent manner. Our results also indicated a significant increase in mitochondrial complex IV activity and membrane potential and a decrease in complex I activity and mitochondrial ROS production in the presence of sodium ions. We propose that inhibition of mitochondrial potassium transport by sodium ions on potassium channel opening could be important for cell protection and ATP synthesis.

Stereological study of the effects of morphine consumption and abstinence on the number of the neurons and oligodendrocytes in medial prefrontal cortex of rats.

Quantitative studies to date on the effects of opioid consumption and abstinence on the nervous system using modern stereological methods have not received enough attention. In addition, they have yielded controversial results. The present study was conducted to investigate the effects of morphine, with or without abstinence, on the neurons and oligodendrocytes of the medial prefrontal cortex (MPFC) in rats using quantitative stereological methods. The male rats were divided into four groups: the first (saline [SAL]) and second (morphine [MOR]) groups were treated with saline and an escalating dose of morphine (5-20 mg/kg) for 30 days, respectively; the third (SAL+abstinence [ABS]) and fourth (MOR+ABS) groups were treated in the same manner as the previous groups plus they had a 30-day abstinence period. The results showed that the volume of the MPFC and its subdivisions decreased by approximately 15% in the MOR group compared with that in the SAL group (P<0.05). In addition, the volume decreased by approximately 24% in the MOR+ABS group compared with that in the SAL+ABS group (P<0.05). The number of neurons in the MOR and MOR+ABS groups decreased by approximately 44% and 35%, respectively, compared with that in their corresponding control groups. Moreover, the number of the oligodendrocytes in the MOR and MOR+ABS groups decreased by approximately 41% and 37%, respectively. No significant difference was noted in the number of cells in the MOR and MOR+ABS groups. In conclusion, morphine consumption leads to a permanent reduction in the number of neurons and oligodendrocytes, and no additional neuron and oligodendrocyte loss occurs after abstinence.