Parker Lindsay M, Kumar Natasha N, Lonergan Tina, McMullan Simon, Goodchild Ann K
The Australian School of Advanced Medicine, Macquarie University, 2 Technology Place, North Ryde, Sydney, NSW, 2109, Australia.
Brain Struct Funct. 2015 Jan;220(1):117-34. doi: 10.1007/s00429-013-0642-3. Epub 2013 Oct 8.
Hypoglycemia elicits physiological and behavioral responses which are mediated in part by neurons within the ventrolateral medulla (VLM). The present study describes the neurochemistry of neurons activated by glucoprivation (2-deoxy-D-glucose, 2DG), specifically those within regions containing the A1, caudal C1 (cC1) and rostral C1 (rC1) cell groups. 2DG induced c-Fos immunoreactivity throughout the VLM. Activated neurons expressing prepro-cocaine and amphetamine-regulated transcript (PPCART), neuropeptide Y (NPY), glutamic acid decarboxylase (GAD67) or prepro-enkephalin (PPE) mRNA and/or immunoreactivity (-ir) for tyrosine hydroxylase (TH) were identified. TH(+) neurons were recruited in a dose-dependent manner. At high doses of 2DG [400 mg/kg, (n = 6)], 76 ± 1.2 % of activated neurons were TH(+) representing 52 ± 1.3 % of the total TH population. Virtually all activated neurons in the A1 and cC1 regions but only 60 % in the rC1 region were TH(+). Within the A1 region, TH(+), TH(+)NPY(+) and TH(+)NPY(+)PPE(+) subpopulations were activated and likely regulate vasopressin, oxytocin, and corticotrophin releasing hormone (CRH) from the hypothalamus. Within the cC1 region, non-TH neurons, TH(+)NPY(+), TH(+)NPY(+)PPCART(+), and TH(+)NPY(+)PPE(+) subpopulations were activated, likely regulating autonomic hypothalamic neurons or CRH and thyrotropin releasing hormone secretion. Within the rC1 region, non-TH neurons (40 % of those activated) were predominantly PPE(+) and were recruited by higher 2DG doses. Of the TH(+) activated neurons in the rC1 region, many expressed PPCART and half expressed NPY. The activated spinally projecting population was almost entirely TH(+)PPCART(+) and is likely to regulate adrenaline and glucagon release. These data indicate that glucoprivation activates at least nine phenotypically distinct populations of neurons in the VLM.
低血糖会引发生理和行为反应,这些反应部分由延髓腹外侧区(VLM)内的神经元介导。本研究描述了由糖剥夺(2-脱氧-D-葡萄糖,2DG)激活的神经元的神经化学特性,特别是那些位于包含A1、尾侧C1(cC1)和头侧C1(rC1)细胞群的区域内的神经元。2DG诱导整个VLM区域的c-Fos免疫反应性。鉴定出表达前脑啡肽原-可卡因和苯丙胺调节转录物(PPCART)、神经肽Y(NPY)、谷氨酸脱羧酶(GAD67)或前脑啡肽原(PPE)mRNA和/或酪氨酸羟化酶(TH)免疫反应性(-ir)的激活神经元。TH(+)神经元以剂量依赖性方式被募集。在高剂量2DG [400 mg/kg,(n = 6)]时,76±1.2%的激活神经元为TH(+),占TH总数的52±1.3%。实际上,A1和cC1区域内所有激活神经元均为TH(+),但rC1区域仅60%的激活神经元为TH(+)。在A1区域内,TH(+)、TH(+)NPY(+)和TH(+)NPY(+)PPE(+)亚群被激活,并可能调节来自下丘脑的血管加压素、催产素和促肾上腺皮质激素释放激素(CRH)。在cC1区域内,非TH神经元、TH(+)NPY(+)、TH(+)NPY(+)PPCART(+)和TH(+)NPY(+)PPE(+)亚群被激活,可能调节自主下丘脑神经元或CRH和促甲状腺激素释放激素的分泌。在rC1区域内,非TH神经元(占激活神经元的40%)主要为PPE(+),并在较高剂量2DG作用下被募集。在rC1区域的TH(+)激活神经元中,许多表达PPCART,一半表达NPY。激活的投射至脊髓的神经元群体几乎全部为TH(+)PPCART(+),并可能调节肾上腺素和胰高血糖素的释放。这些数据表明,糖剥夺激活了VLM中至少9种表型不同的神经元群体。