MONOSYNAPTIC RESPONSES OF THE VENTRAL ROOTS OF THE SPINAL CORD UNDER EXPERIMENTAL HYPOANDROGENEMIA
DOI:
https://doi.org/10.11603/1811-2471.2020.v.i2.11334Keywords:
androgens, castration, motor neurons, spinal cord, bioelectric activityAbstract
There are almost no studies on changes in the bioelectrical activity of spinal cord motor neurons that occur in the long-term period of hypoandrogenemia. This problem is poorly understood and relevant.
The aim – to study of the bioelectrical activity of the motor apparatus of the spinal cord by analyzing induced monosynaptic discharges of the ventral root under experimental hypoandrogenemia 4 months after the start of its modeling
Material and Methods. The study was performed on male Wistar rats aged 5–6 months and weighing 180–260 g, which were divided into experimental (n=10) and control (n=12) groups. An experimental model was created by surgical castration. Evoked activity was withdrawn from an isolated ventral root during stimulation of the proximal portion of the ipsilateral dorsal root of the L5 segment with pulses of 0.3 ms duration and strength from 1 to 5 thresholds. The threshold, chronaxy, latency, amplitude and duration of evoked potentials were analyzed, and the phenomenon of refractoriness was studied by applying paired stimuli with an interval of 1 to 1000 ms. The dynamics of the propagation of excitation on multithreshold neurons was studied using a stimulus of increasing intensity (from 1.1 to 2 P).
Results. In animals with orchiectomy, the threshold of excitation increased by (35.29±8.7) %, chronaxy decreased by (6.2±2.66) %, the duration of the latent period increased by (4.59±0.88) % relative to the corresponding indices of the control group. The use of increasing intensity stimuli revealed a faster increase in the response amplitude in animals with experimental hypoandrogenemia in the interval from 1.1 to 1.6 threshold. When applying paired stimuli, the restoration of the response amplitude to the test stimulus was slower at intervals of 20 to 200 ms.
Conclusions. In the long-term periods of hypoandrogenemia, a relative decrease in the excitation threshold of medium and high threshold motor neurons is observed against the background of a general decrease in their excitability, an increase in latency and a decrease in lability, which is most likely due to an increase in the phenomena of homosynaptic depression.
References
Matsumoto, A., Micevych, P.E., & Arnold, A.P. (1988). Androgen regulates synaptic input to motoneurons of the adult rat spinal cord. Neuroscience, 8(11), 4168-4176. ISSN: 0270-6474 DOI: https://doi.org/10.1523/JNEUROSCI.08-11-04168.1988
Verhovshek, T., Rudolph, L.M., & Sengelaub, D.R. (2013). BDNF and androgen interactions in spinal neuromuscular systems. Neuroscience, 239, 103-114. ISSN: 0270-6474 DOI: https://doi.org/10.1016/j.neuroscience.2012.10.028
Fargo, K.N., Galbiati, M., Foecking, & E.M. (2008). Androgen regulation of axon growth and neurite extension in motoneurons. Hormones and Behavior, 53(5), 716-728. ISSN: 0018-506X DOI: https://doi.org/10.1016/j.yhbeh.2008.01.014
Fargo, K.N., Foecking, E.M., & Jones, K.J. (2009). Neuroprotective actions of androgens on motoneurons. Frontiers in Neuroendocrinology, 30 (2), 130-141. ISSN: 0091-3022 DOI: https://doi.org/10.1016/j.yfrne.2009.04.005
Finsterer, J., & Scorza, F.A. (2019). Central nervous system abnormalities in spinal and bulbar muscular atrophy (Kennedy's disease). Clinical Neurology and Neurosurgery, 184, 105426. DOI: 10.1016/j.clineuro.2019.105426. ISSN: 0303-8467 DOI: https://doi.org/10.1016/j.clineuro.2019.105426
Liu, X., Zhu, M., Li, X., Tang, J. (2019). Clinical manifestations and AR gene mutations in Kennedy's disease. Functional & Integrative Genomics, 19(3), 533-539. DOI: 10.1007/s10142-018-0651-7. ISSN: 1438-7948 DOI: https://doi.org/10.1007/s10142-018-0651-7
Badders, N.M., Korff, A., Miranda, H.C., Vuppala, P.K., Smith, R.B., et al. (2018). Selective modulation of the androgen receptor AF2 domain rescues degeneration in spinal bulbar muscular atrophy. Nature Medicine, 24(4), 427-437. DOI: 10.1038/nm.4500. ISSN: 1078-8956 DOI: https://doi.org/10.1038/nm.4500
McLeod, V.M., Lau, C.L., Chiam, M.D.F., Rupasinghe, T.W., Roessner, U., et all. (2019). Androgen receptor antagonism accelerates disease onset in the SOD1G93A mouse model of amyotrophic lateral sclerosis. British Journal of Pharmacology, 176(13), 2111-2130. DOI: 10.1111/bph.14657. ISSN: 0007-1188 DOI: https://doi.org/10.1111/bph.14657
Rodynskiy, O.G., Tkachenko, S.S., & Huz, L.V. (2015). Monosynaptychni vidpovidi ventralnykh korintsiv spynnoho mozku v umovah eksperymentalnoi menopauzy [Monosynaptic responses of the ventral roots of the spinal cord in experimental menopause]. Klinichna ta eksperymentalna patolohiia – Clinical and Experimental Pathology, 4 (54), 128-132. ISSN 1727-4338
Narayanan, R., Mohler, M.L., & Bohl, C.E. (2008). Selective androgen receptor modulators in preclinical and clinical development. Nuclear Receptor Signaling Atlas, 6, 1-26. DOI: 10.1621/nrs.06010. ISSN: 15507629 DOI: https://doi.org/10.1621/nrs.06010
Hammond, J., Le, Q., & Goodyer, C. (2001). Testosterone-mediated neuroprotection through the androgen receptor in human primary neurons. Journal of Neurochemistry, 77, 1319-1326. DOI: 10.1046/j.1471-4159.2001.00345. ISSN: 0022-3042
Pike, C.J., Carroll, J.C., & Rosario, E.R. (2009). Protective actions of sex steroid hormones in Alzheimer’s disease. Frontiers in Neuroendocrinology, 30 (2), 239–258. DOI: 10.1016/j.yfrne.2009.04.015. ISSN: 0091-3022 DOI: https://doi.org/10.1016/j.yfrne.2009.04.015
Dmitriyeva, O.A., & Sherstyuk, B.V. (2007). Vliyaniye stress-indutsirovannogo snizheniya urovnya testosterona na gistokhimicheskiye izmeneniya polovykh organov krys [The effect of stress-induced decrease in testosterone levels on histochemical changes in genital organs of rats]. Pacific Medical Journal, 3, 55-57. ISSN: 0022-3042
Biatek, M., Zaremba, P., Borowicz, K.K. (2004). Neuroprotective role of testosterone in the nervous system. Polish Journal of Pharmacology, 56 (5), 509-518. ISSN 1230-6002.
Foradori, C.D., Weiser, M.J., & Handa, R.J. (2008). Non-genomic actions of androgens. Frontiers in Neuroendocrinology, 29 (2), 169-181. DOI: 10.1016/j.yfrne.2007.10.005. ISSN: 0091-3022. DOI: https://doi.org/10.1016/j.yfrne.2007.10.005
Asuthkar, S., Demirkhanyan, L., Sun, X., Elustondo, P.A., Krishnan, V., et al. (2015). The TRPM8 protein is a testosterone receptor. The Journal of Biological Chemistry, 290 (5), 2670-88. DOI: 10.1074/jbc.M114.610873. ISSN: 0021-9258. DOI: https://doi.org/10.1074/jbc.M114.610873
Lambert, J.J., Belelli, D., Hill-Venning, C., & Peters, J.A. (1995). Neurosteroids and GABAA receptor function. Trends in Pharmacological Sciences, 16 (9), 295-303. DOI: 10.1016/s0165-6147(00)89058-6. ISSN: 0165-6147. DOI: https://doi.org/10.1016/S0165-6147(00)89058-6
Liu, C., Ward, P.J., & English, A.W. (2014). The effects of exercise on synaptic stripping require androgen receptor signaling. PLoS ONE, 9 (6), e98633. DOI: 10.1371/journal.pone.0098633. ISSN: 1932-6203 DOI: https://doi.org/10.1371/journal.pone.0098633
Hussain, R., Ghoumari, A.M., & Bielecki, B. (2013). The neural androgen receptor: a therapeutic target for myelin repair in chronic demyelination. Brain a Journal of Neurology, 136, 132-146. DOI: 10.1093/brain/aws284. ISSN: 0006-8950 DOI: https://doi.org/10.1093/brain/aws284
Pesaresi, M., Soon-Shiong, R., & French, L. (2015). Axon diameter and axonal transport: In vivo and in vitro effects of androgens. Neuroimage, 115, 191-201. DOI: 10.1016/j.neuroimage.2015.04.048. ISSN: 1053-8119 DOI: https://doi.org/10.1016/j.neuroimage.2015.04.048
