Effects of postnatal ethanol exposure on the development of GABAA receptors in rat brain /
Offspring of alcoholic mothers have an increased risk of growth retardation, facial malformation and neurobehavioral dysfunction. These defects, recognized collectively as the fetal alcohol syndrome (AS) represent a major public health problem. In an attempt to understand cellular mechanisms of neur...
| Main Author: | |
|---|---|
| Format: | Thesis Book |
| Language: | English |
| Published: |
[Place of publication not identified] :
[publisher not identified] ;
1998.
|
| Subjects: | |
| Online Access: | http://proxy.library.tamu.edu/login?url=http://proquest.umi.com/pqdweb?did=732843351&sid=1&Fmt=2&clientId=2945&RQT=309&VName=PQD |
| Summary: | Offspring of alcoholic mothers have an increased risk of growth retardation, facial malformation and neurobehavioral dysfunction. These defects, recognized collectively as the fetal alcohol syndrome (AS) represent a major public health problem. In an attempt to understand cellular mechanisms of neurobehavioral dysfunction in FAS, the present study used a rodent model of FAS to focus on the impact of binge-like ethanol exposure on the early postnatal development of [GABAA] receptor funtion in the rat medial septum/diagonal band (MS/DB) and cerebellum. These brain areas are associated with deficits in leaning/attention and motor impairment in FAS. [GABAA] receptor function represents the primary inhibitory neurotransmitter receptor in the mammalian central nervous system (CNS) and is known to be important in adult ethanol intoxication, as well as playing a unique excitatory role in early neuronal development. Binge-like ethanol exposure was modeled in Sprague-Dawley rat pups. Animals were exposed to ethanol (4.5 g/kg/day) during postnatal days (PD) 4-9 (human third trimester equivalent) using "pup-in-a- cup'' artificial rearing method. GABAA receptor activity was characterized pharmacologically in acutely isolated MS/DB neurons and cerebellar Purkinje neurons, using whole-cell patch clamp electrophysiological recordings. [GABAA] receptor sensitivity to GABA and allosteric modulators changed differentially during first postnatal month in both types of neurons from untreated animals. Generally, GABA sensitivity decreased, while maximum responsiveness increased with age, suggesting the expression of more low sanity receptors with age. As neurons matured, allosteric modulator enhancement generally increased as was exemplified by midazolam, while inhibition decreased as in the case of [Zn2]. Postnatal ethanol exposure substantially blunted the developmental changes in [GABAA] receptor function in both neuronal types. In MS/DB neurons, delayed [GABAA] receptor development recovered by the end of the first postnatal month but loss of allostric inhibition by 30 [jtM Zn2+] was accelerated and remained through the fifth postnatal week. Additional study showed a small rightward shim of the [Zn2+] concentration-inhibition curve suggesting changes in [GABAA] receptor subunit expression may have occurred. These findings show that postnatal ethanol exposure can interfere with [GABAA] receptor maturation. Such abnormal maturation of [GABAA] receptors may play a significant role in neurobehavioral deficits seen in FAS children. |
|---|---|
| Item Description: | Vita. |
| Physical Description: | xii, 125 leaves : illustrations ; 28 cm. Issued also on microfiche from University Microfilm Inc. |
| Bibliography: | Includes bibliographical references: pages 103-124. |