STUDIES OF CENTRAL NERVOUS SYSTEM FUNCTIONAL ANATOMY
中枢神经系统功能解剖学研究
基本信息
- 批准号:2578692
- 负责人:
- 金额:--
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:
- 资助国家:美国
- 起止时间:至
- 项目状态:未结题
- 来源:
- 关键词:brain mapping cannabinoids corticotropin releasing factor cytokine cytokine receptors drug receptors growth factor receptors hypothalamic pituitary axis immunocytochemistry interleukin 1 long term potentiation neurochemistry neuroendocrine system neuropeptides neuropharmacologic agent neurotransmitter metabolism neurotransmitter receptor neurotrophic factors
项目摘要
The Section on Functional Neuroanatomy combines molecular and
neuroanatomical methods to identify dynamic aspects of nervous system
function that relate to issues of mental health, infectious disease, and
drug abuse. Drug and neurotransmitter receptors are mapped using in
vitro ligand binding and autoradiography. In situ hybridization
histochemistry is used to localize and quantify mRNA expression of
neuropeptides, monoamine transporters and synthesizing enzymes,
cytokines, receptors, transcription factors, and immediate-early genes
in studies of adaptive changes to pharmacological, physiological, or
surgical interventions. 1) Expression of the mRNA for the immediate-
early gene c-fos was used to map brain sites responsive to injections of
interleukin-1 or the endotoxin lipopolysaccharide. Responsive cells in
the brainstem suggest a pathway by which peripheral cytokines, as
mediators of immune or inflammatory challenges, affect neuroendocrine
responses. Removal of the area postrema, a circumventricular organ in
the medulla, blocked the responses to intravenous interleukin-1. 2)
Antidepressant drugs (fluoxetine, imipramine, phenelzine, idazoxan) were
administered in an animal study of short- and long-term drug treatment.
Brain systems responsive to long-term therapeutic administration include
the corticotropin-releasing hormone (CRH) component of the hypothalamic
paraventricular nucleus (PVN), which controls the hypothalamic-pituitary-
adrenal (HPA) axis, and the hypothalamic arcuate nucleus, which is the
source of major projections to the PVN and of numerous key neuropeptides
such as neuropeptide Y (NPY) and beta endorphin. The results suggested
that the arcuate NPY and locus coeruleus norepinephrine systems act
coordinately to mediate antidepressant drug effects. Anatomical markers
were combined in arcuate neurons to reveal peptide mRNA levels in neurons
with identified projections to the PVN. Levels were unchanged following
adrenalectomy. 3) A physiological model of memory formation is long-term
potentiation (LTP), which is induced in the hippocampus in vivo by high-
frequency stimulation of the perforant path. Several hours after this
treatment, mRNAs for neurotrophins and neurotrophin receptors (trkB and
trkC) are upregulated in a temporally and spatially discrete fashion.
The data suggest that growth factors underlie the physical changes
associated with memory formation.
功能神经解剖学部分结合了分子和
项目成果
期刊论文数量(0)
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M HERKENHAM其他文献
M HERKENHAM的其他文献
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