The effect of arcuate nucleus transplantation on the development of the anterior pituitary in monosodium glutamate-treated rats

Treatment with monosodium glutamate (MSG) during the neonatal period is known to produce a selective lesion of the arcuate nucleus in rat brain, which is the major site of production of growth hormone releasing-hormone (GRH), followed by a secondary reduction in growth hormone (GH) synthesis in the anterior pituitary. Normal arcuate nuclei from hypothalamic areas of newborn rats were transplanted into the third ventricles of 27-day-old rats which were treated with MSG on alternate days for the first 10 days of life. Ninety days after birth, the anterior pituitaries were examined for GH synthesis by immunohistochemical staining with GH antiserum. The results indicated that the impaired GH synthesis in the anterior pituitary treated with MSG was partially restored in some recipients by grafts of arcuate nuclei in which the GRH-containing neurons were clearly detected by immunohistochemical staining with GRH antiserum.     

Neurotransmitters,neuropeptides and binding sites in the rat mediobasal hypothalamus: effects of monosodium glutamate (MSG) lesions

Summary Indirect immunofluorescence histochemistry and receptor autoradiography were used to study the localization of transmitter-/peptidecontaining neurons and peptide binding sites in the mediobasal hypothalamus in normal rats and in rats treated neonatally with repeated doses of the neurotoxin monosodium-glutamate (MSG). In the arcuate nucleus, the results showed a virtually complete loss of cell bodies containing immunoreactivity for growth hormone-releasing factor (GRF), galanin (GAL), dynorphin (DYN), enkephalin (ENK), corticotropin-like intermediate peptide (CLIP), neuropeptide Y (NPY), and neuropeptide K (NPK). Tyrosine hydroxylase(TH)-, glutamic acid decarboxylase(GAD)-, neurotensin(NT)- and somatostatin(SOM)-immunoreactive (IR) cells were, however, always detected in the ventrally dislocated, dorsomedial division of the arcuate nucleus. In the median eminence, marked decreases in numbers of GAD-, NT-, GAL-, GRF-, DYN-and ENK-IR fibers were observed. The numbers of TH-, SOM-and NPY-IR fibers were in contrast not or only affected to a very small extent, as revealed with the immunofluorescence technique. Biochemical analysis showed a tendency for MSG to reduce dopamine levels in the median eminence of female rats, whereas no effect was observed in male rats. Autoradiographic studies showed high to moderate NT binding sites, including strong binding over presumably dorsomedial dopamine cells. In MSG-treated rats, there was a marked reduction in GAL binding in the ventromedial nucleus. The findings implicate that most neurons in the ventrolateral and ventromedial arcuate nucleus are sensitive to the toxic effects of MSG, whereas a subpopulation of cells in the dorsomedial division of the arcuate nucleus, including dopamine neurons, are not susceptible to MSG-neurotoxicity. The results indicate, moreover that the very dense TH-IR fiber network in the median eminence predominantly arises from the dorsomedial TH-IR arcuate cells, whereas the GAD-, NT-, GAL-, GRF-and DYN-IR fibers in the median eminence to a large extent arise from the ventrolateral arcuate nucleus. Some ENK-and NPK-positive cells in the arcuate nucleus seem to project to the lateral palisade zone of the median eminence, but most of the ENK-IR fibers in the median eminence, located in the medial palisade zone, seem to primarily originate from an area(s) located outside the arcuate nucleus, presumably the paraventricular nucleus. The NPY-positive fibers in the median eminence contain to a large extent immunoreactive dopamine -hydroxylase (DBH), and do not arise from the ventromedial arcuate nucleus. SOM-IR cells in the dorsal periventricular arcuate nucleus do not send major projections to the median eminence. The present findings thus show that MSG treatment represents a valuable tool to clarify the organization of chemically identified neuron populations in the arcuate nucleus-median eminence complex and provide further information for understanding the neuroendocrine effects of neonatal MSG treatment.     

Decreased tuberoinfundibular and pituitary dopamine and dihydroxyphenylacetic acid concentrations in rats with estrogen-induced pituitary tumors

The majority of pituitary adenomas are prolactin (PRL)-secreting, but it is still uncertain whether their pathogenesis results from a central nervous system (CNS) disturbance or autonomous lactotroph growth and function. We have measured dopamine (DA) and dihydroxyphenylacetic acid (DOPAC) concentrations in rats bearing estradiol-induced PRL-secreting pituitary tumors. Female rats, injected at 3-week intervals with 2 mg estradiol valerate (EV), had increased plasma prolactin concentrations, up to 3 micrograms/ml, at 31 weeks. Inversely, there was a reduction of DA and DOPAC in the median eminence and arcuate nucleus as well as a decreased DOPAC/DA ratio in the arcuate nucleus. DA-containing nuclei in the other parts of the brain were not affected. Anterior pituitary weight increased while its DA concentration decreased during estradiol treatment. In the neurohypophysis, DA concentrations were unchanged while DOPAC and the ratio DOPAC/DA decreased following the estrogen treatment. Our data suggest that rats with primary estrogen-induced PRL-secreting tumors have a defect in the CNS-DA neurotransmission.     

The role of dopamine in methylene blue-mediated inhibition of estradiol benzoate-induced anterior pituitary hyperplasia in rats

Recently, we demonstrated that methylene blue partially inhibited estradiol-benzoate-induced anterior pituitary hyperplasia in rats. Since central dopaminergic systems participate in the regulation of estrogen-induced anterior pituitary growth and tumor transformation, this study examined whether a 3-week treatment with methylene blue could affect anterior pituitary levels of dopamine (DA), dihydroxyphenylalanine (DOPA), and dihydroxyphenylacetic acid and dopamine (D-2) receptors in male rats. Compared to controls, methylene blue significantly decreased anterior pituitary weight, increased basal anterior pituitary DA levels, and inhibited estradiol benzoate-induced decreases in anterior pituitary DA concentrations. Furthermore, we found that methylene blue alone decreased anterior pituitary D-2 receptor number. Methylene blue given in combination with estradiol benzoate partially inhibited estradiol benzoate-induced anterior pituitary growth and estradiol benzoate-induced increases in D-2 receptor number. Estradiol benzoate-treated rats had significantly lower anterior pituitary DOPA accumulation after intraperitoneal administration of 3,4-hydroxybenzyl-hydrazine dihydrochloride (NSD-1015), an irreversible inhibitor of L-aromatic amino acid decarboxylase whereas methylene blue did not affect anterior pituitary DOPA accumulation when compared to controls. Methylene blue decreased anterior pituitary prolactin levels and inhibited increases in anterior pituitary prolactin after estradiol benzoate administration. The present results suggest that anterior pituitary DA may play an important role in estrogen-induced anterior pituitary hyperplasia and tumor formation and that antioxidant drugs such as methylene blue may attenuate estrogen-induced pituitary growth. This may occur via increases in anterior pituitary DA levels associated with down-regulation of anterior pituitary D-2 receptors.     

Immunohistochemical evidence of neurons with GHRH or LHRH in the arcuate nucleus of male mice and their possible role in the postnatal development of adenohypophysial cells

Background: The neonatal administration of monosodium L-glutamate (MSG) has been used in investigations of the possible role of the arcuate nucleus in neuroendocrine regulation during postnatal development. We used this method to examine whether the mouse arcuate contained cell bodies immunoreactive with antisera to growth hormone releasing hormone (GHRH) or luteinizing hormone releasing hormone (LHRH), and whether these hypothalamic peptides affect synthesis and secretion of growth hormone and gonadotropin and the testis. Methods: The hypothalamus, pituitary, and testes of adult male mice treated with MSG during the neonatal period were fixed in Bouin's fluid or 10% neutral formalin. The hypothalamus was used in immune staining, the pituitary was used in both morphometry and immune staining, and the testis was stained with hematoxylin and eosin. Results: Body weights in control and treated mice were not different. The treated mice had more subcutaneous adipose tissue and a shorter body than the control mice. The testes were heavier in the controls. Many perikarya immunoreactive with antisera to GHRH or LHRH were found in the arcuate nucleus in control mice, but few such perikarya were found in this nucleus in treated mice. The size of the anterior lobe and the number and size of GH cells, follicle stimulating hormone (FSH) cells, and prolactin (PRL) cells in treated mice were less than those of control mice. Conclusions: GHRH and LHRH neurons in the arcuate nucleus in male mice may cause body and testis weight to increase via GH and LH cells, respectively, in the adenohypophysis during postnatal development. There are some differences in the hypothalamo-pituitary-testis axis of mice and rats. © 1994 Wiley-Liss, Inc.     

A decrease of cytosol estrogen receptors in the hypothalamus as a result of treatment of neonatal rats with glutamate

Summary Experiments were performed to determine whether the neuroendocrine dysfunctions of rats treated neonatally with monosodium glutamate (MSG) could be related to a loss of cytoplasmic estrogen receptors. Female rats treated with MSG as neonates were ovariectomized as adults and killed by decapitation 2 or 3 weeks after ovariectomy. Body, gonadal and anterior pituitary gland weights in MSG-treated rats were depressed when compared to that seen in their littermate controls. Serum prolactin concentration was elevated in the MSG-treated rats. Serum luteinizing hormone (LH) concentration was significantly lower in MSG-treated rats than in controls at 2 weeks, but not at 3 weeks after ovariectomy, suggesting a sluggish postovariectomy rise of serum LH concentration. Serum follicle-stimulating hormone (FSH) concentration was not altered by the MSG treatment. The concentration of cytosol estrogen receptors in the anterior pituitary gland was similar to that of controls, but hypothalamic concentration of estrogen receptors decreased as a result of the MSG treatment. After dissection of different hypothalamic regions, it was found that the greatest depletion of the cytosol estrogen receptors occurred in the arcuate-median eminence region. The results raise the possibility that some reproductive impairments of MSG-treated rats could stem from a decrease in cytosol estrogen receptors in the arcuatemedian eminence region.Supported by grants from the University of Nebraska Medical Center, the NIMH (MH 36419), the NIH (HD11011), and the NSF (BNS 8013050)     

毁损弓状核对动脉粥样硬化形成的影响

本实验分为四组：（1）单纯毁损弓状核组,（2）毁损弓状核＋动脉粥样硬比诱发剂组,（3）单纯给予动脉粥样硬化诱发剂组和（4）对照组,包括腹腔注射生理盐水及皮下注射谷氨酸单钠等2组。在通过电镜观察主动脉壁变化的同时探讨下丘脑弓状核对动脉粥样硬化形成的影响。结果发现：单纯毁损弓状核组血管内皮细胞明显变性,细胞核肿胀,内皮下层增厚并出现空泡,可见有平滑肌细胞向内皮下层迁移,形成明显的动脉粥样硬化早期病变;毁损弓状核＋动脉粥样硬化诱发剂组和单纯用动脉粥样硬化诱发剂组,血管壁的变化基本与单纯毁损弓状核组相同,都有内皮细胞变性,细胞核肿胀,内皮下层增厚和出现空泡等变化,与单纯毁损弓状核组相比未发现有明显不同的变化;对照组未发生任何病理变化。本研究提示下丘脑弓状核对动脉粥样硬化的形成可能有直接调控作用。     

损毁弓状核对大鼠骨组织形态计量学的影响

目的： 研究损毁下丘脑弓状核对大鼠骨组织形态计量学的影响。 方法： SD大鼠于出生后第1、3、5、7、9 d皮下注射10％谷氨酸单钠(MSG)（4 g/kg BW），对照组同法注射等体积生理盐水，并设MSG毒性对照组，于70 d龄同法注射MSG，各组大鼠皆存活至160 d。用3％戊巴比妥钠腹腔麻醉，用4％多聚甲醛经左心室行全身灌注，取脑作下丘脑弓状核冠状面切片，HE染色。取右侧胫骨常规脱钙，石蜡包埋，矢状面连续切片，胶原特殊染色，用于显示骨小梁结构。HE染色用于破骨细胞计数。图像分析仪对弓状核正中隆起切面和骨组织进行照片和计量。用放免法测血清中GH（生长素）、E2（雌二醇）和T（睾酮）含量。 结果： MSG大鼠弓状核神经细胞数量显著减少，GH和E2、T水平明显降低，骨量显著减少，发生骨质疏松，NS组和MSG毒性对照组弓状核、GH、E2、T和骨组织无明显改变。 结论： ①MSG大鼠骨组织的改变不是MSG对垂体和骨组织的毒性作用所致；②下丘脑弓状核参与骨代谢的调控；③通过GH和性激素作用是ARC参与骨代谢调控的重要途径。     

Central but not peripheral glucoprivation is impaired in monosodium glutamate-treated rats

In the present study, newborn male Wistar rats were injected, subcutaneously, five times, every other day, with monosodium glutamate (MSG, 4 g/kg bw) or saline (as control, C), during the neonatal period. MSG animals developed destruction of the arcuate nuclei (ARC) with absence of NPY-immunoreactive cell bodies, which impaired both the food intake (baseline) and the 2-deoxy-D-glucose (2DG) glucoprivic feeding response. Increases in the immunoreactivity of corticotropin-releasing hormone-cell bodies in the paraventricular nuclei might have developed to compensate for the atrophy of the pituitary in MSG-treated rats. After systemic 2DG injection, neither the C nor the MSG rats increased their food intake, but they showed similar hyperglycemic responses, whereas plasma free fatty acids (FFA) increased only in the C group. In other groups, 2DG, norepinephrine (NE), neostigmine (NEO) and saline were intracerebroventricularly (i.c.v.) administered. In this condition, impairment of the hyperglycemic and food intake responses, associated to a lower increase in plasma FFA levels, were observed. As opposed to this, the MSG treatment gives support to NE effects, enhancing food intake, as well as plasma glucose and FFA levels. After NEO, plasma glucose increased only in the MSG group, while plasma FFA levels were elevated in the C rats. Taken together, the results obtained after MSG treatment point to a separate neural control of the hyperglycemic response and of the lipid mobilization when stimulated by central 2DG, NE or NEO administration. It seems likely that the excitatory neural pathway that controls lipid metabolism and is present in C rats was destroyed by the MSG treatment.     

老龄大鼠下丘脑及垂体促肾上腺皮质激素样和β－内啡肽样免疫阳性细胞的相关变化

正常Ｗｉｓｔａｒ大鼠，雌雄不拘，老龄鼠（２０个月）８只，壮龄鼠（８个月）１３只。石蜡切片，ＡＢＣ法染色，ＤＡＢ显色．光镜下观察下丘脑及垂体促肾上腺皮质激素样免疫反应（ＡＣＴＨ－ｉｒ）和β－内啡肽样免疫反应（β－ＥＮｒｙ－ｉｒ）阳性细胞的形态、分布和计数。图像分析仪测其灰度值、结果：下丘脑弓状核β－ＥＮＤ－ｉｒ阳性细胞可分为胞核不明显、着色较深、数量较多的强阳性细胞和胞核明显、着色较淡、数量较少的弱阳性细胞；ＡＣＴＨ－ｉｒ阳性细胞，胞核明显，胞体较大，类似于β－ＥＮＤ－ｉｒ弱阳性细胞。老龄大鼠这两种阳性细胞出现率均明显低于壮龄大鼠。弓状核和垂体前叶ＡＣＴＨ－ｉｒ阳性细胞灰度值老龄鼠显著低于壮龄鼠，而β－ＥＮＤ－ｉｒ阳性细胞灰度值老龄鼠则显著高于壮龄鼠。     

免疫后再感染大鼠下丘脑及垂体ACTH样和β－内啡肽样免疫阳性细胞的相关变化

对经福氏痢疾杆菌免疫后的Ｗｉｓｔａｒ老龄、壮龄大鼠，腹膜腔注入致病量福氏痢疾杆菌Ｆ１ｂ（活菌４９２万个／ｇ体重），２４ｈ后处死取材，用ＡＢＣ法进行免疫组织化学染色．光镜下观察下丘脑及垂体的促肾上腺皮质激素样和卜内啡肽样免疫反应阳性细胞的形态、分布并进行计数，再通过图像分析仪测其灰度值．结果：下丘脑弓状核含此二种活性物质的阳性细胞数量，老龄鼠明显低于壮龄鼠．多数鼠第三脑室室周层出现许多β－内啡肽样强阳性细胞．再感染老龄鼠弓状核促肾上腺皮质激素佯阳性细胞灰度值显著高于再感染壮龄鼠，但其β－内啡肽样阳性细胞灰度值却显著低于再感染壮龄鼠．再感染老龄鼠垂体前叶的此２种活性物质阳性细胞灰度值均显著低于再感染壮龄鼠．提示：弓状核和垂体的促肾上腺皮质激素和β－内啡肽含量的变化以及二者间比例的失调，与老龄鼠免疫功能减退密切相关．     

Neonatal monosodium glutamate dosing alters the sleep-wake cycle of the mature rat

Alterations of the sleep-wake cycle have been studied in male adult rats after neonatal administration of monosodium glutamate (MSG; 4 X 4 mg/g body wt.). Results indicated that MSG treatment caused: an almost complete disappearance of ACTH and alpha-MSH immunoreactive (IR) perikarya in the rostral part of the arcuate nucleus; an increase in total sleep duration with a more pronounced effect on paradoxical sleep. Regarding circadian rhythmicity there was a trend to a decomposition of the 24 h period into ultradian components (12 h, 8 h, 6 h harmonics). The participation of pro-opiomelanocortin peptides in sleep regulation is discussed.     

Hypophysectomy in monosodium glutamate-pretreated rats suppresses paradoxical sleep rebound

Control untreated and pretreated female rats at birth with 10 injections of monosodium glutamate (MSG, 4 mg/g b. wt.) were hypophysectomized (HYPX) at 45-60 days of age and their sleep-waking cycle continuously registered. In control rats, hypophysectomy was followed by a 35.7% decrease in paradoxical sleep (PS) duration while it has no effect on the sleep of MSG-treated rats. After 24 h of PS deprivation, there was a normal immediate rebound of PS in the control HYPX and MSG rats while there was no significant rebound in the HYPX-MSG-treated rats. It is concluded that neuropeptides from arcuate nucleus and hypophysis are involved in a PS rebound mechanism.     

Cocaine place conditioning increases pro-opiomelanocortin gene expression in rat hypothalamus

Recent research suggests an involvement of pro-opiomelanocortin (POMC) gene products in modulating cocaine reward and addiction-like behaviors in rodents. In this study, we investigated whether cocaine-induced conditioned place preference (CPP) alters POMC gene expression in the brain or pituitary of rats. Sprague-Dawley rats were conditioned with 4 injections of 0, 10 or 30 mg/kg cocaine (i.p.) over 8 days and tested 4 days after the last conditioning session. Another group received the same pattern of cocaine injections without conditioning. POMC mRNA levels in the hypothalamus (including arcuate nucleus), amygdala and anterior pituitary, as well as plasma ACTH and corticosterone levels were measured. Cocaine place conditioning at 10 and 30 mg/kg doses increased POMC mRNA levels in a dose-dependent manner in the hypothalamus, with no effect in the amygdala. Cocaine CPP had no effect on POMC mRNA levels in the anterior pituitary or on plasma ACTH or corticosterone levels. In rats that received cocaine at 30 mg/kg without conditioning, there was no such effect on hypothalamic POMC mRNA levels. Alteration of POMC gene expression in the hypothalamus is region-specific after cocaine place conditioning, and dose-dependent. The increased POMC gene expression in the hypothalamus suggests that it is involved in the reward/learning process of cocaine-induced conditioning.     

Specialized junction in the distal convoluted tubule of rat kidney

The effect of the monosodium glutamate (MSG) induced lesion of the arcuate nucleus on catecholamines in the arcuate nucleus and median eminence of the mouse hypothalamus was determined using the Falck-Hillarp histofluorescence technique. The number of fluorescent perikarya in the arcuate nucleus of treated animals was decreased approximately 60%; the fluorescence intensity of surviving neurons was notably reduced. These changes were accompanied by a reduction in the intensity of fluorescence in the median eminence. Pretreatment of control and MSG-lesioned animals with a monoamine oxidase inhibitor (pargyline) greatly increased fluorescence in the median eminence and arcuate nucleus of both groups. However, the number of fluorescing perikarya of the arcuate nucleus of the normal pargyline treated group far exceeded that of the pargyline MSG animals. It is concluded that neonatally administered MSG caused destruction of a large number of dopaminergic arcuate perikarya.     

免疫大鼠下丘脑及垂体ACTH样和β－内啡肽样免疫阳性细胞的相关变化

取正常Ｗｉｓｔａｒ大鼠，雌雄兼用。老龄鼠（２０个月）和壮龄鼠（８个月）各１０只．用福氏痢疾杆菌及福氏完全佐剂免疫动物，免疫成熟后处死取材。石蜡切片，ＡＢＣ法染色，ＤＡＢ显色．光镜下观察下丘脑及垂体促肾上腺皮质激素样免疫反应（ＡＣＴＨ－ｉｒ）和β－内啡肽样免疫反应（β－ＥＮＤ－ｉｒ）阳性细胞的形态、分布和计数。图像分析仪测其灰度值。结果：多数鼠第三脑室室周层出现许多β－ＥＮＤ－ｉｒ强阳性细胞．弓状核ＡＣＴＨ－ｉｒ阳性细胞以及β－ＥＮＤ－ｉｒ阳性细胞数量在被免疫的老、壮龄鼠之间无明显差异．弓状核ＡＣＴＨ－ｉｒ阳性细胞灰度，免疫组老龄鼠低于同组壮龄鼠；而β－ＥＮＤ－ｉｒ阳性细胞灰度则反之。垂体前叶的ＡＣＴＨ－ｉｒ阳性细胞灰度，免疫组老龄鼠高于同组壮龄鼠；βＥＮＤ－ｉｒ阳性细胞灰度，免疫组老、壮龄鼠间无明显差异。表明免疫组老龄鼠神经内分泌与免疫系统间的调节发生紊乱、与正常组比较，除免疫组老龄鼠弓状核ＡＣＴＨ－ｉｒ阳性细胞灰度显著低于正常老龄鼠外，其余各组灰度值皆高于或接近于相应正常组大鼠。     

Effects of electrochemical stimulation of the hypothalamus on serum prolactin and LH in rats

Summary Plasma levels of prolactin and LH were measured by radioimmunoassay following electrochemical stimulation of the medial preoptic area (MPO) or the arcuate nucleus (Arc.N.) in pentobarbital anesthetized proestrous rats. Differences in the secretion pattern of prolactin and LH were observed when stimulated by means of acutely or chronically implanted electrodes. Acute implantation and stimulation of the MPO resulted in no change in serum prolactin levels, whereas stimulation by means of chronically implanted electrodes evoked a marked increase in serum prolactin. The general observation was that electrostimulation in the acute experiments causes a less sharp but more prolonged prolactin and LH release from pituitary than stimulation through chronically implanted electrodes.Aided in part by NIH research grants CA 10771 and AM 4784.     

Divergent effects of acute and chronic monosodium l-glutamate treatment on the anterior and posterior parts of the arcuate nucleus

Young albino rats were injected with either single or repeated doses of 0.1–6.0 mg/g body weight of monosodium l-glutamate between the ages of 2 and 40 days. The smallest, single effective dose was 0.25 mg/g body weight administered during the first week of life. The sensitivity to monosodium l-glutamate decreased with age. Monosodium l-glutamate caused nuclear pyknosis and edematous swelling of neurons in the anterior part of the arcuate nucleus which is located at the level of the ventromedial nucleus. These effects resulted in a reduction of neurons in this region. All of the doses used were ineffective in producing necrosis or cell death in the posterior part of the arcuate nucleus which is found at the level of the premamillary nuclei. The number of neurons in the arcuate nucleus of control animals was 46,500 with a neuron/glia ratio of 1.22. The anterior part of the arcuate nuclus had 55% of the neurons.Adult animals with an 80–90% loss of neurons in the anterior part of arcuate nucleus showed marked adiposity, hypoactivity, decreased body length, tail automutilation and reduced endocrine organ weight. The histological appearance of the ovaries, testes and pituitary glands was normal. The sexual behavior of these rats was normal, but the females were not fertile.The results of this study indicate that monosodium l-glutamate has a regional effect on the arcuate nucleus. These data also indicate that the majority of the neurons in the anterior arcuate region do not play a definitive role in the basal regulation of gonadotrophic hormones.     

Neural transplants. effects On startle responses in neonatally MSG-treated rats

Neonatal monosodium glutamate (MSG) treatment has been associated with dysfunctions in stress responses. Therefore, the present study aimed at examining the acoustic startle response (ASR) in MSG-treated rats and the effects of fetal neural transplantation. Male and female rats were given MSG (4 mg/g) or saline on alternate days from days 2-10 after birth. To determine whether fetal transplants could reverse behavioral impairments observed in MSG-treated rats, at 12 days of age MSG-treated rats received either arcuate nucleus (AN), cortical fetal grafts, or sham surgery into the third ventricle. ASR amplitude was measured at 35-40 days of age, and again in adulthood. MSG produced the expected decrease in the density of hypothalamic neuropeptide Y (NPY) and tyrosine hydroxylase (TH) in the AN area. Corticotropin-releasing factor (CRF) neurons/fibers were not affected by MSG. Pituitary atrophy was observed in all MSG rats. We report a permanent increase in the amplitude and reduction in short-term habituation of ASR in all MSG-treated rats. No effect was observed on long-term habituation in male rats. Cortical, but not AN tissue significantly reduced the magnitude of ASR in MSG animals. The results are discussed in terms of the central pathways mediating ASR, in particular hypothalamo-amygdala connections. It is considered that nonspecific factors mediate recovery produced by cortical tissue grafts, as observed in other models of neural transplantation.     

Degeneration of dopaminergic neurons triggers an expression of individual enzymes of dopamine synthesis in non-dopaminergic neurons of the arcuate nucleus in adult rats

Non-dopaminergic neurons expressing individual complementary enzymes dopamine (DA) synthesis were shown to produce DA in cooperation [Ugrumov, M., Melnikova, V., Ershov, P., Balan, I., Calas A., 2002. Tyrosine hydroxylase- and/or aromatic L-amino acid decarboxylase-expressing neurons in the rat arcuate nucleus: ontogenesis and functional significance. Psychoneuroendocrinology 27, 533-548; Ugrumov, M.V., Melnikova, V.I., Lavrentyeva, A.V., Kudrin, V.S., Rayevsky, K.S., 2004. Dopamine synthesis by non-dopaminergic neurons expressing individual complementary enzymes of the dopamine synthetic pathway in the arcuate nucleus of fetal rats. Neuroscience 124, 629-635]. This study was aimed at testing our hypothesis that the cooperative synthesis of DA in non-dopaminergic neurons is an adaptive reaction under functional insufficiency of the dopaminergic system. Functional insufficiency of the tuberoinfundibular dopaminergic system was provoked by 6-OHDA-induced degeneration of dopaminergic neurons in the arcuate nucleus in adult rats. Bienzymatic (dopaminergic) neurons and monoenzymatic neurons expressing tyrosine hydroxylase (TH) or aromatic L-amino acid decarboxylase (AADC) were detected with a double-immunofluorescent technique on cryostat sections. The 6-OHDA-induced degeneration of dopaminergic neurons was accompanied by a significant increase of the number of monoenzymatic TH neurons and AADC neurons that appears to support our hypothesis. The reaction of bienzymatic and monoenzymatic neuron populations to the 6-OHDA administration occurred to be region-specific. The former disappeared in the dorsomedial region of the arcuate nucleus while the latter increased in the ventrolateral region. Thus, degeneration of dopaminergic neurons in the arcuate nucleus of adult rats is accompanied by the expression of individual enzymes of DA synthesis in non-dopaminergic neurons that may be an adaptive reaction.