Biomedical subjects

Jessica Strömberg

Publications and source records attributed to Jessica Strömberg.

2 recordsLinked to original sources

PubMed2003

Allopregnanolone-stimulated GABA-mediated chloride ion flux is inhibited by 3beta-hydroxy-5alpha-pregnan-20-one (isoallopregnanolone).

Altered gamma-aminobutyric acid (GABA)-ergic function is associated with neurological and psychiatric disorders. Certain progesterone metabolite 3alpha-hydroxy-5alpha-pregnan-20-one, or allopregnanolone (ALLO), increases the GABA-mediated chloride ion (Cl(-)) flux through GABA(A) receptors in a similar fashion as benzodiazepines and barbiturates. We have studied the effect of its 3beta diastereomer, 3beta-hydroxy-5alpha-pregnan-20-one, or isoallopregnanolone (ISO), on the Cl(-) flux and investigated the interaction between ISO and ALLO on GABA-mediated Cl(-) uptake in cortical homogenates from adult male Wistar rats. We found that ISO from 1 microM to 1 mM does not affect baseline Cl(-) uptake in rat cortical homogenates. Neither does ISO at dose range of 100 nM to 100 microM interact with 10 microM GABA in the Cl(-) uptake assay. In addition, ISO at the dose range of 1-30 microM does not affect flunitrazepam and pentobarbital-induced increase of Cl(-) uptake. We conclude that ISO selectively inhibits the ALLO-induced Cl(-) uptake with respect to ALLO concentrations. The IC(50) of ISO inhibition on 1 microM ALLO-induced Cl(-) uptake was calculated to be 12.25 microM. On the other hand, we have studied the effect of 30 microM ISO on ALLO (0.01 nM to 1 microM) induced displacement of tert-butylbicyclophosphorothionate (TBPS) binding. We did not note any interaction between ALLO and ISO on TBPS binding assay. These results indicate that ISO may be useful functional blocker of GABA(A) receptor potentiating steroid ALLO when used at concentrations that do not affect baseline GABAergic neurotransmission.

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PubMed2003

Pathogenesis in menstrual cycle-linked CNS disorders.

That 3alpha-hydroxy-5alpha/beta-pregnane steroids (GABA steroids) have modulatory effects on the GABA-A receptor is well known. In behavioral studies in animals high exogenous dosages give concentrations not usually reached in the brain under physiological conditions. Animal and human studies show that GABA-A receptor-positive modulators like barbiturates, benzodiazepines, alcohol, and allopregnanolone have a bimodal effect. In pharmacological concentrations they are CNS depressants, anesthetic, antiepileptic, and anxiolytic. In low dosages and concentrations, reached endogenously, they can induce adverse emotional reactions in up to 20% of individuals. GABA steroids can also induce tolerance to themselves and similar substances, and rebound occurs at withdrawal. Menstrual cycle-linked disorders can be understood by the concept that they are caused by the action of endogenously produced GABA-steroids through three mechanisms: (a) direct action, (b) tolerance induction, and (c) withdrawal effect. Examples of symptoms and disorders caused by the direct action of GABA steroids are sedation, memory and learning disturbance, clumsiness, increased appetite, worsening of petit mal epilepsy, negative mood as tension, irritability and depression during hormone treatments, and the premenstrual dysphoric disorder (PMDD). A continuous exposure to GABA steroids causes tolerance, and women with PMDD are less sensitive to GABA-A modulators. A malfunctioning GABA-A receptor system is related to stress sensitivity, concentration difficulties, loss of impulse control, irritability, anxiety, and depression. An example of withdrawal effect is "catamenial epilepsy," when seizures increase during menstruation after the withdrawal of GABA steroids. Similar phenomena occur at stress since the adrenals produce GABA steroids during stress.

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