DISTRIBUTION OF GABA TRANSPORTER (GAT1) LEVELS IN THE BÖTZINGER COMPLEX AT THE EARLY STAGES OF POSTNATAL DEVELOPMENT IN RATS WITH PRENATAL SEROTONIN DEFICIENCY

Abstract

Objective - to study the distribution of GABA transporter 1 (GAT1) levels in the Bötzinger complex at the early stages of postnatal development in rats with prenatal serotonin deficiency. Materials and methods. The work was carried out on Wistar line laboratory rats. To reduce the level of endogenous serotonin in the embryonic period, the method of tryptophan hydroxylase inhibition by para-chlorophenylalanine (PCPA) (Sigma, USA) was used. The GAT1 transport protein was detected by immunohistochemical reaction with anti-GABA transporter1 primary rabbit polyclonal antibodies (AbCam, UK). The brain was examined on the 5th, 10th and 20th day of postnatal development. Results. At the early stages of postnatal development, a fluctuation in the GAT1 level of the GABA transporter was noted in the Bötzinger complex of control animals. In the first postnatal week, the GAT1 level was high both in the network of neuronal processes and terminals, and in synapses. During the 2nd week of life, the GAT1 level decreased, and by the end of the 3rd week it increased again, reaching the initial level. Deficiency of serotonin in the prenatal period caused a significant increase in the level of GAT1 in the neuropil of the Bötzinger complex in experimental animals at all studied stages of postnatal development. Conclusions. Prenatal deficiency of serotonin leads to a significant increase in the GAT1 level at the early stages of postnatal development, which can lead to a change in the GABA transmission, and, as a result, to a disturbance in the balance of inhibitory and stimulatory effects in the respiratory nuclei.

Keywords

GAT-transporter / Bötzinger complex / serotonin / early postnatal development period

References

[1] Хожай Л. И., Ильичева Н. В. Формирование ГАМК-ергической нейральной сети в комплексе Бетцингера у крыс в ранний постнатальный период в норме и при дефиците эндогенного серотонина // Морфология. 2016. Т. 150, вып. 4. С. 44-49.

[2] Хожай Л. И., Шишко Т. Т. Изменение структурной организации бледного ядра шва при снижении содержания эндогенного серотонина в пренатальный период развития у крыс // Морфология. 2013. T. 143, вып. 2. С. 75-78.

[3] Alheid G. F., McCrimmon D. R. The chemical neuroanatomy of breathing // Respir. Physiol. Neurobiol. 2008. Vol. 164. Iss. 1-2. P. 3-11. doi: 10.1016/j.resp.2008.07.014

[4] Augood S. J., Herbison A. E., Emson P. C. Localization of GAT-1 GABA Transporter mRNA in Rat Striatum: Cellular Coexpression with GAD67 mRNA, GAD67 Immunoreactivity, and Parvalbumin mRNA // J. Neurosci. 1995. Vol. 15. Iss. l. P. 665-674. doi: 10.1523/JNEUROSCI.15-01-00865.1995

[5] Barakat L., Bordey A. GAT-1 and Reversible GABA Transport in Bergmann Glia in Slices // J. Neurophysiol. 2002. Vol. 88. Iss. 3. P. 1407-1419. doi: 10.1152/jn.2002.88.3.1407

[6] Bernstein E. M., Quick M. W. Regulation of γ-aminobutyric acid (GABA) transporters by extracellular GABA // J. Biol. Chem. 1999. Vol. 274, № 2. P. 889-895. doi: 10.1074/jbc.274.2.889

[7] Danbolt N. C. Glutamate uptake // Prog. Neurobiol. 2001. Vol. 65. Iss. 1. P. 1-105. doi: 10.1016/s0301-0082(00)00067-8

[8] Gadea A., Lopez-Colome A. M. Glial transporters for glutamate, glycine, and GABA: II. GABA transporters // J. Neurosci. Res. 2001. Vol. 63. Iss. 6. P. 461-468. doi: 10.1002/jnr.1040

[9] Guthmann A., Fritschy J. M., Ottersen O. P. et al. GABA, GABA transporters, GABA(A) receptor subunits, and GAD mRNAs in the rat parabrachial and Kölliker-Fuse nuclei // J. Comp. Neurol. 1998. Vol. 400. Iss. 2. P. 229-243. doi: 10.1002/(SICI)1096- 9861(19981019)400:2<229::AID-CNE5>3.0.CO;2-B

[10] Isaacson J. S. Synaptic transmission: Spillover in the spotlight // Curr. Biol. 2000. Vol. 10. Iss. 13. P. 475-477. doi: 10.1016/ s0960-9822(00)00551-0

[11] Isaacson J. S., Solis J. M., Nicoll R. A. Local and diffuse synaptic actions of GABA in the hippocampus // Neuron. 1993. Vol. 10. Iss. 2. P. 165-175. doi: 10.1016/0896-6273(93)90308-e

[12] Kuwana S., Okada Y., Sugawara Y. et al. Disturbance of neural respiratory control in neonatal mice lacking GABA synthesizing enzyme 67-kDa isoform of glutamic acid decarboxylase // Neuroscience. 2003. Vol. 120. Iss. 3. P. 861-870. doi: 10.1016/ s0306-4522(03)00338-5

[13] Lehre K. P., Rusakov D. A. Asymmetry of glia near central synapses favors presynaptically directed glutamate escape // Biophys. J. 2002. Vol. 83. Iss. 1. P. 125-134. doi: 10.1016/ S0006-3495(02)75154-0

[14] Paxinos G., Watson C. The Rat Brain in stereotaxic coordinates. London: Academic Press, 1998.

[15] Ritter B., Zhang W. Early postnatal maturation of GABAA-mediated inhibition in the brainstem respiratory rhythm-generating network of the mouse // Eur. J. Neurosci. 2000. Vol. 12. Iss. 8. P. 2975-2984. doi: 10.1046/j.1460-9568.2000.00152.x

[16] Song G., Li Q, Shao F. Z. GABAergic neurons in Kölliker-Fuse nucleus and Bötzinger complex with axons projecting to phrenic nucleus // Sheng Li Xue Bao. 2000. Vol. 52, № 2. P. 167-169.

[17] Yu S. Y., Wang G. M., Wang H. et al. Raphe pallidus modulates Botzinger complex-induced inhibition of the phrenic nerve in rats // Eur. J. Neurosci. 2011. Vol. 34. Iss. 7. P. 1113-1120. doi: 10.1111/j.1460-9568.2011.07837.x

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Khozhai L.I.