The ketogenic diet (KD) has been used to treat intractable childhood epilepsy. However, its mechanism of action remains unknown. In the present study, we examined the effects of KD on the expression of multiple constituents of the GABAergic system in the hippocampus through immunohistochemistry and northern blot analysis. From the results, we have shown that KD increased expression of GABA and decreased GABA transporter1 (GABATp) and GABA transaminase (GABA-T) mRNA levels in the hippocampus. These results suggest that the neuroinhibitory effect of KD may be mediated, at least in part, by the increment of GABAergic activity in the hippocampus. KD may increase the GABA levels in the synaptic space by limiting GABA reuptake and in the presynaptic nerve terminal by inhibiting GABA degradation.
4-Aminobutyrate Transaminase ; Animals ; Blotting, Northern ; Epilepsy ; gamma-Aminobutyric Acid* ; Glutamate Dehydrogenase ; Hippocampus* ; Immunohistochemistry ; Ketogenic Diet* ; Mice* ; RNA, Messenger

OBJECTIVES: Changes of GABAergic neurotransmission in response to the application of different types of environmental stress have been the subject of research for over two decades. However, the nature of the changes induced by stress appear to show a dependent phenomena on the type and duration of stressor agent employed. METHODS: For this reason, this study was performed to observe the effects of repeated stress on the radioligands binding to GABA A/benzodiazepine receptors of discrete brain regions. The author also examined the activity of GABA transaminase and the concentration of endogenous GABA. Male Sprague-Dawley rats, weighing 150-200g were forced to suffer an immobilization stress for 2 hours during 14 consecutive days. RESULTS: Repeated immobilization stress decreased the binding of [3H]flunitrazepam on the benzodiazepine receptor in the cortex, hippocampus and hypothalamus. Saturation experiments followed by scatchard analyses of the results showed decreased density of benzodiazepine receptor and the affinity remained unchanged. Repeated immobilization stress did not affect the binding of [3H]muscimol on the GABAA receptor, the activity of GABA transaminase, and the concentration of endogenous GABA in the brain regions. CONCLUSIONS: From these results, it can be concluded that repeated immobilization stress modulated GABAergic neurotransmission via downregulation of the benzodiazepine receptor in the brain.
4-Aminobutyrate Transaminase ; Animals ; Brain ; Down-Regulation ; gamma-Aminobutyric Acid ; Hippocampus ; Humans ; Hypothalamus ; Immobilization ; Male ; Rats* ; Rats, Sprague-Dawley ; Receptors, GABA ; Receptors, GABA-A ; Synaptic Transmission*

PURPOSE: The aim of this study was to investigate the effects of testosterone deprivation on urinary bladder in male rabbits by proteomic analysis. MATERIALS AND METHODS: New Zealand white male rabbits (2.5-3 kg) were divided into 2 group; control group with 5 rabbits and bilateral orchiectomized group, bilateral orchiectomized group was divided into post-operative 4 weeks group (group 1), and 8 weeks group (group 2) with 5 rabbits respectively. Bladder wall was excised partly at 4 or 8 weeks from the beginning of the experiment. Conventional proteomics was performed with high resolution 2-D gel electrophoresis followed by computational image analysis and protein identification using mass spectrometry. We decided to consider 'significant' if protein had 50% decreasing or 200% increasing expression rate. RESULTS: Six proteins were significantly changed in orchiectomy group, compared to control group; serum albumin precursor, GABA transaminase, dimethylarginine dimethylaminohydrolase 2, serum/glucocorticoid regulated kinase and LOC304923 protein were over-expressed in both group 1 and group 2. Annexin A1 was significantly over-expressed in the group 2 only. CONCLUSION: An overexpression of Annexin A1 and GABA transaminase mean a processing of neuronal reactions to injury in orchiectomized rabbit bladder. Also an overexpression of dimethylarginine dimethylaminohydrolase 2 would increase NO synthesis and thereby promote re-endothelialization in the rabbit bladder after orchiectomy. Serum/glucocorticoid regulated kinase would relate to Na+ transport. Albumin precursor and LOC304923 protein are remained to further research. These data suggested that bilateral orchiectomy would make the urinary bladder unstable. However more information is needed in human bladder tissue.
4-Aminobutyrate Transaminase ; Annexin A1 ; Electrophoresis, Gel, Two-Dimensional ; Humans ; Male ; Mass Spectrometry ; Neurons ; New Zealand ; Orchiectomy* ; Phosphotransferases ; Proteomics ; Rabbits ; Serum Albumin ; Testosterone ; Urinary Bladder*

Established antiepileptic drugs (AEDs) decrease membrane excitability by interacting with neurotransmitter receptors or ion channels. AEDs developed prior to 1980 appear to act on sodium channels, gamma-amino butyric acid type A (GABA(A)) receptors or calcium channels. Benzodiazepines and barbiturates enhance GABA(A) receptormediated inhibition. Barbiturates increase the duration of chloride channel opening and at higher doses, they block voltage-dependent calcium channels presynaptically, decreasing excitatory amino acid (EAAs) transmission. Benzodiazepines also interact with the GABA(A) receptor complex and increase the frequency of chloride channel opening. Phenytoin, carbamazepine and possibly sodium valproate decrease high frequency repetitive firing of action potentials by enhancing sodium channel inactivation. At higher doses, PHT may block sodium channels presynaptically and decrease EAAs release. In addition to the action on sodium channel, CBZ interacts with adenosine receptor and decrease C-AMP, and block reuptake of norepinephrine. VPA shows diverse mechanisms including sodium channel blocking. It increases synaptosomal GABA by increasing production and decreasing break-down and interacts with T-type calcium channels preventing thalamocortical interaction necessary for absence. Ethosuximide and sodium valproate reduce a low threshold (T-type) calcium channel current. The mechanisms of action of newly developed AEDs are not fully established. Felbamate is broad-spectrum, and probably has multiple actions on sodium channels, interaction with GABA(A) receptors, and interaction with NM.D.A receptors. Gabapentin binds to a high affinity site on neuronal membranes in a restricted regional distribution of the CNS. This binding site may be related to a possible active transport process of gabapentin into neurons. However this has not proven and the mechanism of action of gabapentin remains uncertain. It is structurally related to GABA and its action of antiepileptic activity is suspected due to change of neuronal amino acids (interfere glutamate synthesis, block GABA uptake, and enhance GABA release). Lamotrigine, initially developed as an antifolate drug, decreases sustained high frequency repetitive firing of voltage-dependent sodium action potentials that may result in a preferential decreased release of presynaptic glutamate. It may also interact with GABA receptors but its primary antiepileptic action is on the sodium channel similar to the PHT and CBZ. Because of such a diverse mechanism of action, LTG is one of the wide spectrum AEDs. Oxcarbazepine's mechanism of action is not known ; however, its similarity in structure and clinical efficacy to that of carbamazepine suggests that its mechanism of action may involve inhibition of sustained high frequency repetitive firing of voltage-dependent sodium action potentials. Vigabatrin is a "designer" drug as is developed rationally, and it reversibly inhibits GABA transaminase, the enzyme that degrades GABA, thereby producing greater available pools of presynaptic GABA for release in central synapses. Increased activity of GABA at postsynaptic receptors may underlie the clinical efficacy of VGB. Tiagabine is a potent blocker of GABA re-uptake by glia and neuron.
4-Aminobutyrate Transaminase ; Action Potentials ; Amino Acids ; Anticonvulsants* ; Barbiturates ; Benzodiazepines ; Binding Sites ; Biological Transport, Active ; Butyric Acid ; Calcium Channels ; Calcium Channels, T-Type ; Carbamazepine ; Chloride Channels ; Ethosuximide ; Excitatory Amino Acids ; Fires ; gamma-Aminobutyric Acid ; Glutamic Acid ; Ion Channels ; Membranes ; Neuroglia ; Neurons ; Neurotransmitter Agents ; Norepinephrine ; Phenytoin ; Receptors, GABA ; Receptors, GABA-A ; Receptors, Neurotransmitter ; Receptors, Purinergic P1 ; Sodium ; Sodium Channels ; Synapses ; Valproic Acid ; Vigabatrin