Effect of Combined Frequency Stimulation on The Electrophysiology of Granule Neurons in The Hippocampal Dentate Gyrus Area of Hindlimb Unloading Mice / 生物化学与生物物理进展

ObjectiveIn recent years, the negative impact of microgravity on astronauts’ nervous systems has received widespread attention. The repetitive transcranial magnetic stimulation (rTMS) technology has shown significant positive effects in the treatment of neurological and psychiatric disorders. The potential benefits of combined frequency stimulation (CFS) which combines different frequency stimulation patterns in ameliorating neurological dysfunctions induced by the microgravity environment, still require in-depth investigation. Exploring the therapeutic effects and electrophysiological mechanisms of CFS in improving various neurological disorders caused by microgravity holds significant importance for neuroscience and the clinical application of magnetic stimulation. MethodsThis study employed 40 C57BL/6 mice, randomly divided into 5 groups: sham group, hindlimb unloading (HU) group, 10 Hz group, 20 Hz group, and combined frequency stimulation (10 Hz+20 Hz, CFS) group. Mice in all groups except the sham group received 14 d of simulated microgravity conditions along with 14 d of repetitive transcranial magnetic stimulation. The effects of CFS on negative emotions and spatial cognitive abilities were assessed through sucrose preference tests and water maze experiments. Finally, patch-clamp techniques were used to record action potentials, resting membrane potentials, and ion channel dynamics of granule neurons in the hippocampal dentate gyrus (DG) region. ResultsCompared to the single-frequency stimulation group, behavioral results indicated that the combined frequency stimulation (10 Hz+20 Hz) significantly improved cognitive impairments and negative emotions in simulated microgravity mice. Electrophysiological experiments revealed a decrease in excitability of granule neurons in the hippocampal DG region after HU manipulation, whereas the combined frequency stimulation notably enhanced neuronal excitability and improved the dynamic characteristics of voltage-gated Na+ and K+ channels. ConclusionThe repetitive transcranial magnetic stimulation with combined frequencies (10 Hz+20 Hz) effectively ameliorates cognitive impairments and negative emotions in simulated microgravity mice. This improvement is likely attributed to the influence of combined frequency stimulation on neuronal excitability and the dynamic characteristics of Na+ and K+ channels. Consequently, this study holds the promise to provide a theoretical basis for alleviating cognitive and emotional disorders induced by microgravity environments.

Effects of repetitive transcranial magnetic stimulation on neuronal excitability and ion channels in hindlimb unloading mice / 生物医学工程学杂志

Weightlessness in the space environment affects astronauts' learning memory and cognitive function. Repetitive transcranial magnetic stimulation has been shown to be effective in improving cognitive dysfunction. In this study, we investigated the effects of repetitive transcranial magnetic stimulation on neural excitability and ion channels in simulated weightlessness mice from a neurophysiological perspective. Young C57 mice were divided into control, hindlimb unloading and magnetic stimulation groups. The mice in the hindlimb unloading and magnetic stimulation groups were treated with hindlimb unloading for 14 days to establish a simulated weightlessness model, while the mice in the magnetic stimulation group were subjected to 14 days of repetitive transcranial magnetic stimulation. Using isolated brain slice patch clamp experiments, the relevant indexes of action potential and the kinetic property changes of voltage-gated sodium and potassium channels were detected to analyze the excitability of neurons and their ion channel mechanisms. The results showed that the behavioral cognitive ability and neuronal excitability of the mice decreased significantly with hindlimb unloading. Repetitive transcranial magnetic stimulation could significantly improve the cognitive impairment and neuroelectrophysiological indexes of the hindlimb unloading mice. Repetitive transcranial magnetic stimulation may change the activation, inactivation and reactivation process of sodium and potassium ion channels by promoting sodium ion outflow and inhibiting potassium ion, and affect the dynamic characteristics of ion channels, so as to enhance the excitability of single neurons and improve the cognitive damage and spatial memory ability of hindlimb unloading mice.

Influence of Hindlimb-unloading on the Morphology of Nerve Endings in Soleus Muscle Spindles / 航天医学与医学工程

Objective To investigate changes induced by hindlimb unloading in morphology of nerve endings in soleus muscle spindles.Method Hindlimb unloading model was simulated by tail suspension in female rats.Fast silver-staining was used to observe morphology of nerve endings of single muscle spindle in 7 d,14 d,21 d and 28 d tail-suspended and control rats.Result Nerve endings of muscle spindles in control rats were intact and clear,and there was no obvious abnormality in single soleus muscle spindle of 7 d tail-suspended rats.Slight fragmentation of nerve endings was observed in Equatorial Region of soleus muscle spindle in 14 d tail-suspended rats,while reduction in density and disruption of nerve endings were observed in soleus muscle spindle in 21 d tail-suspended rats.Serious degeneration and distortion of nerve endings were found in soleus muscle spindle in 28 d tail-suspended rats.Conclusion Hindlimb-unloading can induce time-related changes in morphology of nerve endings of muscle spindle in rats soleus muscle.

Morphological changes in rat testes after Hindlimb Unloading model / 항공우주의학회지

BACKGROUND: The purpose of this study was to examine histological changes of testes induced by hindlimb unloading & position change of testis in mature adult male rats. METHOD: Eight month old (390~410g) 36 male Sprague-Dawley rats were weight-matched assigned to Ground Control (GC), Hindlimb Unloading (HU), Hindlimb Unloading & Testis Tie(HUT), Intra-abdominal Testis(IAT) for 24 days. Daily body weight was watched for status of animal. Testis weight, Seminiferous Tubule Diameter(STD), Seminiferous Tubule Perimeter(STP), Serminiferous Tubule Area(STA), Sertori Cell Height(SCH) were examined in each group. RESULTS: The 24-day hindlimb unloading of HU, HUT and IAT showed no significant change of body weight compared to GC. HUT maintained the weights, STD, STP, STA, SCH of their testes as GC while HU, IAT had significantly decreased the weights, STD, STP, STA of their testes. CONCLUSION: These results support that hindlimb unloading experiment induces serious morphological changes of testes. Therefore, on the hindlimb unloading experiment, IAT should be avoid or the effect of IAT should be correct. It will be necessary to study the pure effect of hindlimb unloading without IAT on the musculoskeltal system and so on which are associated with testosterone.

Effect of Hindlimb Unloading of the Mechanical Properties of Bone in Mature Adult Male Rats: with Emphasis on the Bone Strength / 항공우주의학회지

BACKGROUND: The purpose of this study was to examine site-specific bone strength changes induced by hindlimb unloading in mature adult male rats. METHODS: Eight month old (390-410 g) 26 male Sprague-Dawley rats were weight-mated assigned to either a Ground control (CON) or a Hindlimb Unloading (HU) for 24 days. Daily body weight was watched for status of animal. Weight, BMD, strength, geometry of femur, tibia and humerus were examined in both groups. RESULTS: The 24-day hindlimb unloading of HU showed no significant change of body weight, total bone mineral, and bone geometry compared to CON. HU showed that the upper limb had maintained total bone mineral, bone geometry, and bone mechanical strength compared to CON. The hindlimb of HU had significantly decreased bone strength and ultimate stress (F/B) compared to CON. DEXA analysis of BMD and BMC in HU showed inconsistent changes at femur and tibia, although a relatively constant increase was shown in humerus. In HU rats, mechanical stress testing of compulsive fracture showed that more significant decreases in UL (ultimate load) and ultimate stress (F/B) was seen in femur than in tibia. CONCLUSION: These results support the theory that hindlimb unloading contribute to deleterious effects in femur rather than in tibia. It induced higher loss of mechanical bone strength in femur. In testing for BMD, pQCT, 2D, or 3D is recommended. DEXA is not recommended because it has inconsistent results and limitation with respect to the characteristics of area BMD (g/cm2) as a surrogate of volume BMD (g/cm3).

Nonuniform change in rat soleus muscle fibers after hindlimb suspension / 体力科学

The present study was designed to determine whether conversion of fiber types (type I to II) induced by hindlimb unloading (HU) is identical along the length of fibers in the soleus (SOL) muscle. After 1 and 2 wk HU, SOL was divided into three (proximal, middle and distal) regions and the fiber type composition was determined using myosin adenosinetriphosphatase (ATPase) . There was no significant change in fiber type distribution after 1 wk of HU. The percentage of type I fibers significantly decreased in the proximal and middle regions and that of type IIc fibers increased in all regions after 2 wk of HU. The percentage of type IIc fibers greatly increased in the proximal and middle regions compared with the distal region. Serial cross-sections every 300μm were processed for myosin ATPase from the middle to the distal region, and then analyzed to show the differences in staining characteristics along the length of single fibers. After 2 wk of HU, some of the fibers (3.1±1.2%) displayed changes in the staining characteristics of myosin ATPase (pH 10.3) ; 84% of these fibers identified type IIc fibers in the middle region were observed as type I fibers in the distal region. These results suggest that muscle fibers in unloaded SOL may not transform synchronously or uniformly along their length