Captopril reduces aortic and microvascular growth in hypertensive and normotensive rats

This experiment was designed to investigate the effect of converting enzyme inhibition on functional and structural vascular alterations in one-kidney, one clip hypertensive rats and in normotensive rats. Starting 1 day before surgery, 100 mg/kg/day captopril was given chronically to half of the hypertensive and normotensive groups in their drinking water. With use of intravital microscopy in the cremaster muscle, arteriolar dimensions were measured 4 weeks later, both before and after topical application of 10(-3) M adenosine. Mean blood pressure was 124 +/- 4 mm Hg in control rats and 103 +/- 5 mm Hg in captopril-treated control rats (p less than 0.05). Mean blood pressure was significantly elevated to 183 +/- 5 mm Hg in captopril-treated one-kidney, one clip hypertensive rats and 193 +/- 5 mm Hg in one-kidney, one clip hypertensive rats. With use of histological techniques, a marked reduction of medial-intimal area of the abdominal aorta was found in captopril-treated control rats (24%), and hypertrophy of the aortic wall in one-kidney, one clip hypertensive rats was decreased 26% by captopril. Structural diameter reductions occurred in large arterioles of the captopril-treated control and hypertensive groups and the nontreated hypertensive group. In spite of a significant increase in wall-to-lumen ratio of first-order arterioles in all captopril-treated rats, captopril decreased cross-sectional wall area of these vessels 37% in hypertensive and 20% in control rats, respectively. Measured by stereological techniques, small arteriolar density decreased 30% in captopril-treated hypertensive rats and 17% in captopril-treated control rats. Therefore, smaller arteriolar lumens, decreased aortic and arteriolar cross-sectional wall area, and arteriolar rarefaction after converting enzyme inhibition, in spite of rising or falling blood pressure, are evidence that vascular growth was inhibited in vivo.     

Bromocriptine reduces steatosis in obese rodent models

BACKGROUND/AIMS: Obesity is a risk factor for glucose intolerance, steatosis, and oxidative stress, characteristics of nonalcoholic fatty liver disease. Bromocriptine may have anti-obesity, insulin-sensitizing, lipolytic, and antioxidant properties. We, therefore, hypothesized that bromocriptine would improve markers of nonalcoholic fatty liver disease in obese rodent models. METHODS: We performed a randomized, controlled experiment in genetically obese fatty Zucker rats and diet-induced obese rats to assess for behavioral and peripheral anti-obesity actions of bromocriptine (10mg/kg) that would improve nonalcoholic fatty liver disease. RESULTS: Behaviorally, food intake decreased and locomotor activity increased in bromocriptine-treated fatty Zucker and dietary-induced obese rats. Peripherally, liver triglycerides were significantly reduced and hepatic manganese superoxide dismutase significantly increased in bromocriptine-treated fatty Zucker and diet-induced obese rats compared to controls. Blood glucose was significantly lower in bromocriptine-treated Zucker rats compared to fatty controls and was no different than that of lean controls. CONCLUSIONS: Improvements in obesigenic behaviors, glucose tolerance, hepatic lipid accumulation, and mitochondrial oxidative stress observed in genetically obese and diet-induced obese rodents indicate that bromocriptine may be promising as a broad-based therapy for nonalcoholic fatty liver disease.     

波生坦抑制低氧介导的大鼠肺动脉中5-羟色胺转运体的过度表达

目的 观察5-羟色胺转运体（5-HTT）在低氧性肺动脉高压（HPH）大鼠肺动脉中的表达,探讨波生坦对其肺动脉中5-HTT表达的影响.方法 30只雄性SD大鼠随机分为对照组（C组）、低氧组（H组）和波生坦组（B组）（每组10只）.C组于正常环境中饲养3周,其余2组置于低压低氧舱中饲养3周.B组大鼠予以波生坦100mg·kg^-1·d^-1灌胃,H组按体质量同体积蒸馏水灌胃.测定各组大鼠的平均肺动脉压力（mPAP）、右心室收缩压（RVSP）.免疫组织化学和Western-blot方法分别观察和测定大鼠肺动脉和肺组织中5-HTT的表达水平.结果 H组大鼠的mPAP和RVSP明显高于C组（P值均＜0.05）;和H组大鼠相比,B组大鼠mPAP和RVSP均显著降低（P值均＜0.05）.免疫组织化学和Western-blot结果显示：和C组相比,H组大鼠肺动脉和肺组织中5-HTT的表达明显升高,而B组大鼠肺动脉和肺组织中5-HTT的表达明显低于H组.结论 HPH大鼠肺动脉和肺组织中5-HTT呈过表达,而波生坦可以显著抑制低氧介导的大鼠肺动脉和肺组织中5-HTT的表达增多,这可能是波生坦的新的药理机制之一.     

脂联素改善低氧诱导的大鼠肺微血管内皮细胞功能障碍及机制研究

目的研究重组人球状脂联素(APN)改善低氧诱导的大鼠肺微血管内皮细胞(PMVECs)功能障碍,探讨其潜在的分子机制。方法取SD雄性大鼠PMVECs原代培养,传至第三代行细胞鉴定;PMVECs分3组,常氧(210ml/L O_2,37℃)组;低氧(20 ml/L O_2,37℃)组;低氧(20 ml/L O_2,37℃)+APN(1μg/ml)处理组,分别培养3 h、6 h、9 h和12 h,收集细胞上清测NO浓度;3组PMVEC行RT-PCR测定eNOS基因表达;BCA法测定各组总蛋白含量;行Western blot检测AMPK/p-AMPK、PI3K/p-PI3K、Akt/p-Akt和eNOS/p-eNOS表达。结果 (1)鉴定培养细胞为PMVECs;(2)在相应时间点,与正常组比较,低氧诱导的NO浓度、eNOS mRNA表达水平、总蛋白表达显著下降(P0.01);与低氧组对比,低氧+APN组显著增加了低氧诱导的NO浓度、eNOS mRNA表达水平、总蛋白表达(P0.01);(3)3组AMPK、PI3K、Akt和eNOS总蛋白表达水平不变;与正常组比较,低氧诱导的AMPK、PI3K、Akt、eNOS磷酸化表达水平下降(P0.05);与低氧组对比,低氧+APN组增加了低氧诱导的AMPK、PI3K、Akt、eNOS磷酸化表达水平(P0.05)。结论在细胞水平上,APN能改善低氧条件下诱导的PMVECs功能障碍,促进肺血管具有舒张作用的NO产生,其可能机制可能是伴随着AMPK/PI3K/Akt/eNOS/NO信号通路的激活,APN可能成为潜在治疗低氧性肺动脉高压的辅助药物。     

Aging reduces neural specialization in ventral visual cortex

The present study investigated whether neural structures become less functionally differentiated and specialized with age. We studied ventral visual cortex, an area of the brain that responds selectively to visual categories (faces, places, and words) in young adults, and that shows little atrophy with age. Functional MRI was used to estimate neural activity in this cortical area, while young and old adults viewed faces, houses, pseudowords, and chairs. The results demonstrated significantly less neural specialization for these stimulus categories in older adults across a range of analyses.     

Aging reduces the cardioprotective effect of ischemic preconditioning in the rat heart

Multiple brief periods of ischemia in the mammalian heart elicits protection against morphologic and functional damage caused by longer-duration ischemia. Preconditioning-induced protection against post-ischemic contractile dysfunction has been reported to be depressed with aging of the adult heart. This study was undertaken to determine whether aging of the adult myocardium reduces the preconditioning-induced attenuation of necrosis observed with ischemia. Isolated, perfused hearts obtained from Fischer 344 rats of either 3 (young) or 22 (aged) months of age were paced and instrumented for determination of developed left ventricular pressure. Necrosis was determined with triphenyltetrazolium. In the absence of preconditioning, young and aged adult hearts made globally ischemic for 45 min developed necrosis involving 53+/-6% and 49+/-6% of the myocardium, respectively. Contractile function (+dP/dt(max)) at 90 min of reperfusion was depressed by 80% in young and 52% in aged hearts, compared to values obtained prior to preconditioning. Preconditioning with two 5 min ischemia/5 min reperfusion cycles significantly reduced necrosis development and enhanced reperfusion contractile function in young hearts. However, in aged adult hearts, the preconditioning did not significantly reduce the development of necrosis or enhance reperfusion contractile function. These data suggest that aging reduces the effectiveness of preconditioning in providing cardioprotection against ischemic-induced myocardial necrosis.     

Peptide XIB13 reduces capillary leak in a rodent burn model

ObjectiveEdema due to capillary leak is a generalized and life threatening event in sepsis and major burns for which there is no causal treatment. Local burn wounds are an ideal model to investigate the impact of a new therapeutic agent on edema formation. We aimed to identify peptide sequences of cingulin that can attenuate stress-induced endothelial cytoskeleton disarrangement in vitro and which reduce burn-induced edema in vivo.MethodsCingulin-derived peptides were screened in high content cell culture assays monitoring actin displacement and endothelial cell/cell contacts. The ears of male hairless mice (n = 44) were inflicted with full thickness burns using a hot air jet. Mice with and without burn injuries were treated with Xib13 or solvent by continuous intraperitoneal application for 3 days. Edema, microcirculation, leukocyte-endothelial interactions and angiogenesis – measured as non-perfused area – were investigated over a 12-day period using intravital fluorescence microscopy.ResultsXib13 reduced endothelial stress formation and stabilized endothelial tight junctions in cell-cultures. In the burn model, Xib13 improved angiogenesis compared to controls (non-perfused area on day 12: 5.7 ± 1.5% vs. 12.0 ± 2.1%; p < 0.05). Edema was significantly reduced at all observation points in Xib13-treated animals as compared to controls (day 12: 67.6 ± 2.6% vs. 83.2 ± 6.4%).ConclusionXib13 improved angiogenesis, reduced edema formation and showed no side effects on other physiological parameters. Since edema formation is a serious parameter for burn conversion and is associated with survival it could provide a new treatment option for patients with burn injuries.     

Citrulline diet supplementation improves specific age-related raft changes in wild-type rodent hippocampus

The levels of molecules crucial for signal transduction processing change in the brain with aging. Lipid rafts are membrane microdomains involved in cell signaling. We describe here substantial biophysical and biochemical changes occurring within the rafts in hippocampus neurons from aging wild-type rats and mice. Using continuous sucrose density gradients, we observed light-, medium-, and heavy raft subpopulations in young adult rodent hippocampus neurons containing very low levels of amyloid precursor protein (APP) and almost no caveolin-1 (CAV-1). By contrast, old rodents had a homogeneous age-specific high-density caveolar raft subpopulation containing significantly more cholesterol (CHOL), CAV-1, and APP. C99-APP-Cter fragment detection demonstrates that the first step of amyloidogenic APP processing takes place in this caveolar structure during physiological aging of the rat brain. In this age-specific caveolar raft subpopulation, levels of the C99-APP-Cter fragment are exponentially correlated with those of APP, suggesting that high APP concentrations may be associated with a risk of large increases in beta-amyloid peptide levels. Citrulline (an intermediate amino acid of the urea cycle) supplementation in the diet of aged rats for 3 months reduced these age-related hippocampus raft changes, resulting in raft patterns tightly close to those in young animals: CHOL, CAV-1, and APP concentrations were significantly lower and the C99-APP-Cter fragment was less abundant in the heavy raft subpopulation than in controls. Thus, we report substantial changes in raft structures during the aging of rodent hippocampus and describe new and promising areas of investigation concerning the possible protective effect of citrulline on brain function during aging.

Electronic supplementary material

The online version of this article (doi:10.1007/s11357-012-9462-2) contains supplementary material, which is available to authorized users.     

Aging reduces venous distensibility and the venodilatory response to nitroglycerin in normal subjects

To determine if aging alters venous tone, venous distensibility was measured during control conditions and after the administration of nitroglycerin (0.8-mg spray) to 50 subjects ranging in age from 21 to 78 years. The mean arterial pressure decreased and the heart rate increased significantly after nitroglycerin. Control venous distensibility, measured after the inflation of an upper arm cuff to 30 mm Hg above cuff zero (VV[30]) was 2.69 +/- 1.26 (standard deviation) cc/100 cc arm. The VV[30] increased to 3.06 +/- 1.43 cc/100 cc arm after the administration of nitroglycerin. There was a significant relation between age and baseline venous distensibility (r = 0.53, p less than 0.001) and between age and the change in venous distensibility after nitroglycerin (r = 0.56, p less than 0.001). Both baseline venous distensibility and the venodilatory response to nitroglycerin decreased with age. There was no significant relation between systemic arterial pressure and baseline venous distensibility or between arterial pressure and the venodilatory response to nitroglycerin. Aging appears to diminish baseline venous distensibility and attenuate the venodilatory response to nitroglycerin.     

Hypotensive therapy reduces microvascular albumin leakage in insulin-dependent diabetic patients with nephropathy

The effect of hypotensive therapy on the transcapillary escape rate of albumin (TERalb) was studied in eight hypertensive insulin-dependent diabetic patients (mean age 29, range 19-42 years) with nephropathy and retinopathy. Transcapillary escape rate of albumin (initial disappearance of intravenously injected 125I-labelled human serum albumin), urinary albumin excretion rate (radial immunodiffusion), and glomerular filtrate rate (single bolus 51-Cr-EDTA technique) were measured. After hypotensive treatment (mean duration, 23 months, range 7-39 months) with combinations of metoprolol, hydralazine, and frusemide or thiazide diuretics, arterial blood pressure fell from 152/103 +/- 18/6 mmHg (mean +/- SD) to 133/81 +/- 12/10 mmHg (p less than 0.01), transcapillary escape rate of albumin from 10.2 +/- 1.8 to 8.1 +/- 1.8% of intravascular mass of albumin/h (p less than 0.01), albuminuria from 1803 (370-5066) micrograms/min to 940 (101-2676) micrograms/min (median and range, p less than 0.05), and glomerular filtration rate from 103 +/- 23 to 84 +/- 22 ml/min/1.73 m2 (p less than 0.01). Our study suggests that effective hypotensive treatment reduces the abnormally elevated albumin leakage characteristically found in insulin-dependent diabetic patients with clinical microangiopathy. This may be due to a reduction in the hydrostatic pressure in the microcirculation.     

Bromocriptine reduces growth hormone in acromegaly

We assessed serum growth hormone (GH) levels in ten patients with acromegaly during a 24-hour profile and a 75-g oral glucose tolerance test (GTT). Serum GH levels were measured after five weeks of bromocriptine mesylate therapy, 20 mg daily (P1), after five weeks without bromocriptine mesylate therapy (P2), and again five weeks following restarting treatment with bromocriptine, 20 mg daily (P3). During the 24-hour profile, the following occurred: (1) mean serum GH level of the group was lower during P1 (20.5 mU/L) and P3 (20.8 mU/L) than P2 (49.6 mU/L); (2) in six individual patients during P1 and P3, there was a significant reduction in the mean serum GH value; and (3) a marked circadian variation in the serum GH value was present both with and without the drug therapy in five patients. During the GTT, the mean serum GH value was lower during P1 (18.4 mU/L) and P3 (16.7 mU/L) than P2 (43.3 mU/L), and in seven individual patients during P1 and P3, there was a significant reduction in the mean serum GH value. Overall, a clear reduction in serum GH values due to bromocriptine was demonstrated. In individual patients, serum GH values during a 24-hour profile and GTT gave similar indications of response.     

Juvenile emotional experience alters synaptic composition in the rodent cortex, hippocampus, and lateral amygdala

A quantitative anatomical study in the rodent anterior cingulate and somatosensory cortex, hippocampus, and lateral amygdala revealed region-, cell-, and dendrite-specific changes of spine densities in 3-week-old Octodon degus after repeated parental separation. In parentally separated animals significantly higher spine densities were found on the apical and basal dendrites of the cingulate cortex (up to 143% on apical and 138% on basal dendrite). Branching order analysis revealed that this effect is seen on all segments of the apical dendrite, whereas on the basal dendrites significantly higher spine densities were seen only on the outer branches (third to fifth dendritic segments). Increased spine densities were also observed on the hippocampal CA1 pyramidal neurons (up to 109% on the distal apical segments and up to 106% on the basal segment) compared with the control group. In contrast, significantly reduced spine densities were observed on the granule cell dendrites in the dentate gyrus (down to 92%) and on the apical dendrites in the medial nucleus of the amygdala (down to 95%). No significant changes of spine densities were seen in the somatosensory cortex (except for an increase in the proximal apical segments) and in the lateral nucleus of the dorsal amygdala (except for an increase in the proximal basal dendritic segments). These results demonstrate that repeated stressful emotional experience alters the balance of presumably excitatory synaptic inputs of pyramidal neurons in the limbic system. Such experience-induced modulations of limbic circuits may determine psychosocial and cognitive capacities during later life.     

Aging and the growth hormone/insulin like growth factor-I axis

Growth hormone release and IGF-I synthesis decrease with increasing age. The regulation of the GH/IGF-I system is dependant on the integrity of the hypothalamus, pituitary and liver. During aging there are several changes which contribute to the decline in GH/IGF-I including changes in signal to the somatotrophs from growth hormone releasing hormone, somatostatin and other factors such as body composition, exercise, diet and sleep. All of these factors are discussed in detail within this review. The phenotypic similarities between aging and adult growth hormone deficiency syndrome combined with this decrease in GH/IGF-I with aging have prompted the question whether aging is a GH deficient state. The advent of recombinant growth hormone has led to a number of studies treating elderly patients with GH alone or in combination with sex steroids or exercise. The results of these studies would not back up the use of GH in elderly non-hypopituitary patients as they did not show efficacy, showed high rates of adverse events and there is also some evidence associating GH/IGF-I and risk of neoplasia. If GH therapy is to be used in this cohort of patients further long term efficacy and safety studies are required.     

The microvascular response to growth factors in the hamster cheek pouch

Summary Implicit in attempts to characterize and purify biologically active factors is the premise that the bioassay system employed will show a progressive increase in the response as the concentration of the responsible factor increases. We employed the hamster cheek pouch to assay the neovascularization potential of growth factors, including endothelial cell growth supplement (ECGS), epidermal growth factor (EGF), fibroblast growth factor (FGF) and platelet-derived growth factor (PDGF). Each growth factor was applied to the system in graded concentration and two approaches used to assess neovascularization: first, direct serial inspection of the cheek pouches at 40 power; second, tritiated thymidine incorporation into endothelial cells, assessed by radioautography. PDGF induced a dose-related increase in neovascularization, with a threshold dose of 17.5 g/ml and a peak, 56% response, at a PDGF concentration of 175 g/ml. Progressive increases in PDGF concentration, thereafter, induced progressive reductions in the neovascularization rate. Under some conditions optimal bioassay requires serial dilutions of the assay material over a wide range.     

Thyroid hormone insufficiency during brain development reduces parvalbumin immunoreactivity and inhibitory function in the hippocampus

Thyroid hormones are necessary for brain development. gamma-Amino-butyric acid (GABA)ergic interneurons comprise the bulk of local inhibitory circuitry in brain, many of which contain the calcium binding protein, parvalbumin (PV). A previous report indicated that severe postnatal hypothyroidism reduces PV immunoreactivity (IR) in rat neocortex. We examined PV-IR and GABA-mediated synaptic inhibition in the hippocampus of rats deprived of thyroid hormone from gestational d 6 until weaning on postnatal d 30. Pregnant dams were exposed to propylthiouracil (0, 3, 10 ppm) via the drinking water, which decreased maternal serum T(4) by approximately 50-75% and increased TSH. At weaning, T(4) was reduced by approximately 70% in offspring in the low-dose group and fell below detectable levels in high-dose animals. PV-IR was diminished in the hippocampus and neocortex of offspring killed on postnatal d 21, an effect that could be reversed by postnatal administration of T(4). Dose-dependent decreases in the density of PV-IR neurons were observed in neocortex and hippocampus, with the dentate gyrus showing the most severe reductions (50-75% below control counts). Altered staining persisted to adulthood despite the return of thyroid hormones to control levels. Developmental cross-fostering and adult-onset deprivation studies revealed that early postnatal hormone insufficiency was required for an alteration in PV-IR. Synaptic inhibition of the perforant path-dentate gyrus synapse evaluated in adult offspring, in vivo, revealed dose-dependent reductions in paired pulse depression indicative of a suppression of GABA-mediated inhibition. These data demonstrate that moderate degrees of thyroid hormone insufficiency during the early postnatal period permanently alters interneuron expression of PV and compromises inhibitory function in the hippocampus.     

Methylprednisolone reduces airway microvascular permeability but not airway resistance induced by N-formylmethionine leucyl-phenylalanine in the rabbit

OBJECTIVE: The aim of this study was to determine the effect of corticosteroids on the increase in airway microvascular permeability (MVP) and airway resistance induced by N-formylmethionine leucyl-phenylalanine in the rabbit. METHODOLOGY: After pretreatment with methylprednisolone (for 1 day or 1 week) rabbits were nebulized with N-formylmethionine leucyl-phenylalanine and MVP was assessed using the Evans blue dye technique (on the trachea, bronchi and bronchioles), while airway resistance was measured using a volume displacement plethysmograph. RESULTS: There were no significant differences in airway resistance between the steroid treated group and the control group for either steroid treatment regime. The degree of extravasation of Evans blue dye was significantly inhibited in the bronchioles after both the 1-day and 1-week treatment with methylprednisolone. There were no significant differences in MVP in the trachea or bronchi between the treated groups and the control groups. CONCLUSION: These results show that methylprednisolone can significantly reduce N-formylmethionine leucyl-phenylalanine-induced MVP without affecting airway resistance.     

Intestinal microvascular growth during maturation in diabetic juvenile rats

To determine if intestinal microvascular growth is impaired in diabetic juvenile animals, a segment of the terminal ileum was marked and the microvasculature of this segment observed at the age of 5 weeks and again at the age of 10-11 weeks in normal and diabetic Sprague Dawley rats. Diabetes was induced by streptozotocin after the first observation period and the plasma glucose concentration exceeded 500 mg% by the age of 10-11 weeks. Microvascular growth was quantitated by measurements of the number, length, and maximally dilated inner diameters of specific arterioles and by intercapillary distances in the marked intestinal region at both ages. Although intestinal enlargement was much greater in diabetics, there was no change in the number of arterioles during maturation and intercapillary distances were equivalent in diabetic and normal rats. In normal and diabetic animals, the arteriolar length increased to match bowel elongation, however, increases in bowel and arteriolar lengths in diabetic animals were about twice that of normal rats. During juvenile maturation, the maximally dilated inner diameters of the small arterioles in diabetic animals were increased compared with their normal counterparts. Thus, arteriolar growth during maturation is characterized by changes in the length but not in the number of vessels in intestine of both normal and diabetic rats. The perfusion of about 90% more tissue by mass for each arteriole in diabetic rats is facilitated by arteriolar dilation.(ABSTRACT TRUNCATED AT 250 WORDS)     

Melatonin reduces microvascular damage and insulin resistance in hamsters due to chronic intermittent hypoxia

Abstract: Obstructive sleep apnea (OSA) causes intermittent hypoxia (IH) associated with hypertension, insulin resistance and a systemic inflammatory response. We evaluated the effects of melatonin on vasodilation, capillary perfusion in hamster cheek pouch and insulin resistance, hypertension, and reactive oxygen species (ROS) and nitrate/nitrite levels after IH for 4 wk. Syrian hamsters were divided into four groups: control group (CON), IH group, and melatonin (10 mg/kg) intraperitoneally administered daily for 4 wk/30 min before intermittent air (MEL) or IH (IH + MEL) exposure. IH alone caused elevated blood pressure, increased hematocrit, fasting hyperglycemia, elevated ROS and nitrite/nitrate levels, and vasoconstriction and reduced microvascular perfusion. Melatonin treatment of IH‐exposed animals decreased blood pressure, blood glucose, and ROS and nitrite/nitrate levels, and increased vasodilation and capillary perfusion. An oral glucose tolerance test was performed after 4 wk of IH. During the last 30 min of the hyperinsulinemic euglycemic clamp, blood glucose, and insulin levels were identically matched between groups, but the glucose infusion rate was significantly reduced in IH (29.9 ± 1.9 mg/kg/min) versus IH + MEL group (45.4 ± 1.5 mg/kg/min, P < 0.05) demonstrating a decrease in insulin sensitivity. These results suggest that ROS and nitrite/nitrate levels play important roles in the microvascular dysfunction in IH and that this process is attenuated by melatonin. In conclusion, protection induced by melatonin against functional and metabolic impairment in IH is related to the regulation of ROS and nitrite/nitrate levels in the microcirculation. These observations may have importance to OSA pathological changes.     

Methylphenidate disrupts cytoskeletal homeostasis and reduces membrane-associated lipid content in juvenile rat hippocampus

Although methylphenidate (MPH) is ubiquitously prescribed to children and adolescents, the consequences of chronic utilization of this psychostimulant are poorly understood. In this study, we investigated the effects of MPH on cytoskeletal homeostasis and lipid content in rat hippocampus. Wistar rats received intraperitoneal injections of MPH (2.0 mg/kg) or saline solution (controls), once a day, from the 15th to the 44th day of age. Results showed that MPH provoked hypophosphorylation of glial fibrillary acidic protein (GFAP) and reduced its immunocontent. Middle and high molecular weight neurofilament subunits (NF-M, NF-H) were hypophosphorylated by MPH on KSP repeat tail domains, while NFL, NFM and NFH immunocontents were not altered. MPH increased protein phosphatase 1 (PP1) and 2A (PP2A) immunocontents. MPH also decreased the total content of ganglioside and phospholipid, as well as the main brain gangliosides (GM1, GD1a, and GD1b) and the major brain phospholipids (sphingomyelin, phosphatidylcholine, phosphatidylethanolamine, phosphatidylinositol, and phosphatidylserine). Total cholesterol content was also reduced in the hippocampi of juvenile rats treated with MPH. These results provide evidence that disruptions of cytoskeletal and lipid homeostasis in hippocampus of juvenile rats are triggers by chronic MPH treatment and present a new basis for understanding the effects and consequences associated with chronic use of this psychostimulant during the development of the central nervous system.