Vpliv možganskega področja na lastnosti privzema histamina v astrocite : diplomska naloga

Raztresen, Andreja (author), Kržan, Mojca (mentor)

Glijo so dolgo casa opisovali kot pasivno in nevzdražno vezivno tkivo. Danes vemo, da ima glija zelo kompleksno vlogo. Astrociti kot najbolj razprostranjena in hkrati najštevilcnejša vrsta celic glije v osrednjem živcevju opravljajo razlicne vloge v razlicnih življenjskih obdobjih, med drugim intenzivno sodelujejo pri inaktivaciji številnih nevrotransmiterjev. V astrocitih so dokazali prisotnost transportnih proteinov in encimov, ki razgrajujejo številne nevrotransmiterje, tudi za biogene amine. Ceprav specificnega transporterja za histamin še niso identificirali, obstajajo podatki, da astrociti privzemajo histamin. Histamin kot nevrotransmiter tesno sodeluje pri vseh osnovnih možganskih funkcijah, vkljucen pa je tudi v patofiziologijo nekaterih bolezenskih stanj. Histaminergicni nevroni izhajajo iz tuberomamilarnega jedra v posteriornem bazalnem hipotalamusu, od koder projecirajo prakticno v celotne možgane in del hrbtenjace. Gostota histaminergicnih vlaken je razlicna v razlicnih regijah. V možganski skorji in striatumu je histaminergicnih nevronov vec kot v malih možganih. Zaradi slednjega dejstva in zaradi razlicnih vlog histamina v razlicnih regijah možganov smo raziskovali, kako se razlikujejo lastnosti privzema histamina v kulture astrocitov, pripravljene iz razlicnih možganskih regij neonatalnih podgan. V naši raziskavi so nas zanimale kineticne in farmakološke lastnosti privzema histamina v kulture astrocitov, pripravljene iz malih možganov in striatuma 3 dni starih podgan. Želeli pa smo tudi preveriti morebitno vpletenost OCT-jev (angl. OCT - organic cation transporter - transporter organskih kationov) v privzem histamina. Od kineticnih lastnosti transporta smo proucevali casovno in koncentracijsko odvisnost, izvedli pa smo tudi inhibicijsko študijo z uporabo razlicnih inhibitorjev privzema. Rezultati naših raziskav kažejo, da poteka privzem histamina v astrocitne kulture obeh preiskovanih regij, in sicer vsaj preko dveh mehanizmov. Obstajajo precejšnje razlike pri privzemu 3H-histamina v kulture astrocitov, pripravljene iz razlicnih možganskih regij neonatalnih podgan. Transportni sistem striatuma ima veliko vecjo kapacitivnost. Privzem histamina v astrocitne kulture striatuma poteka hitreje in z veliko vecjo afiniteto kot v astrocitne kulture cerebeluma. Privzem histamina verjetno ne poteka preko OCT. Farmakološka karakterizacija privzema pa je pokazala, da je dezipramin inhibiral privzem histamina v astrocitne kulture striatuma, na privzem histamina v cerebelarne astrocitne kulture pa ni imel vpliva.Rezultati diplomskega dela predstavljajo dodaten dokaz, da imajo astrociti razlicne funkcije v razlicnih možganskih regijah.

• Language: Slovenian
• Keywords: astrociti glija histamin možgani nevrotransmiterji
• Work type: Undergraduate thesis
• Typology: 2.11 - Undergraduate Thesis
• Organization: FFA - Faculty of Pharmacy
• Place of publishing: Ljubljana
• Publisher: [A. Raztresen]
• Year: 2010
• Number of pages: XI, 58 f.
• PID: 20.500.12556/RUL-121340
• UDC: 577
• COBISS.SI-ID: 2893169
• Publication date in RUL: 05.10.2020

Secondary language

• Language: English
• Title: Brain region-dependent characteristics of histamine transport into astrocytes

Abstract

Astrocytes, the most abundant cells within the human brain were far long considered as passive, connective tissue. Nowadays, we are aware that astrocytes have a complex function in different phases of brain development and maturation. They also actively participate in the inactivation of neurotransmitters. Thus they express different transporters and enzymes, which take part in the metabolism of neurotransmitters. Histamine transport has not been elucidated, yet. Nevertheless, it has been reported that astrocytes take up histamine. Neurotransmitter histamine is involved in many brain functions and ethiopatogenesis of many neurological diseases. Histaminergic neurons originate in the tuberomammillary nucleus of posterior basal hypothalamus and project into different brain and spinal regions. The density of histaminergic innervations is brain-region dependent. Cortex and striatum possess more histaminergic innervations than cerebellum. Due to this fact and brain-region dependent role of histamine, we decided to investigate the characteristics of histamine uptake in astrocytes raised from rat striatum and cerebellum. We focused our study toward kinetic and pharmacological properties of histamine transport in primary astrocytes cultures, raised from newborn rat cerebellum and striatum. Next goal was to check whether the possible role of OCT (OCT-organic cation transporter) in histamine innervations. We investigated time and concentrations-dependent kinetic parameters and the influence of different compounds on histamine uptake. Our results showed that histamine is taken up into astrocytes from both brain regions by two different mechanisms. There is a big difference of histamine uptake into astrocytes from different brain-regions. Histamine uptake is higher into striatal astrocytes. Organic cation transporters are not involved in histamine transport. The rate and affinity of histamine uptake is significantly higher for striatal than in cerebellar astrocytes. Desipramine, inhibits the uptake of histamine only into striatal astrocytes, but has no influence on histamine uptake into glial cells from cerebellum. Our results provide additional evidence for the brain-region specific function of astrocytes.