Lipid Peroxidation In Cerebral Cortex Research Articles

A Purine Derivative Containing an Organoselenium Group Protects Against Memory Impairment, Sensitivity to Nociception, Oxidative Damage, and Neuroinflammation in a Mouse Model of Alzheimer's Disease.

In the present study, the effect of 6-((4-fluorophenyl) selanyl)-9H-purine (FSP) was tested against memory impairment and sensitivity to nociception induced by intracerebroventricular injection of amyloid-beta peptide (Aβ) (25-35 fragment), 3nmol/3μl/per site in mice. Memory impairment was determined by the object recognition task (ORT) and nociception by the Von-Frey test (VFT). Aβ caused neuroinflammation with upregulation of glial fibrillary acidic protein (GFAP) (in hippocampus), nuclear factor-κB (NF-κB), and the proinflammatory cytokines interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α) in cerebral cortex and hippocampus. Additionally, Aβ increased oxidant levels and lipid peroxidation in cerebral cortex and hippocampus, but decreased heme oxygenase-1 (HO-1) and peroxiredoxin-1 (Prdx1) expression in the hippocampus. Anti-neuroinflammatory effects of FSP were demonstrated by a decrease in the expression of GFAP and NF-κB in the hippocampus, as well as a decrease in proinflammatory cytokines in both the hippocampus and cerebral cortex FSP protected against oxidative stress by decreasing oxidant levels and lipid peroxidation and by increasing HO-1 and Prdx1 expressions in the hippocampus of mice. Moreover, FSP prevented the activation of nuclear factor erythroid 2-related factor 2 (Nrf-2) in the hippocampus of mice induced by Aβ. In conclusion, treatment with FSP attenuated memory impairment, nociception sensitivity by decreasing oxidative stress, and neuroinflammation in a mouse model of Alzheimer's disease.

An evaluation of in vitro and in vivo free radical scavenging and antioxidant potential of ethanolic extract of Pergularia daemia

Oxidative stress plays a major role in developing chronic, degenerative, cardiovascular and neurodegenerative diseases caused by excessive production of reactive oxygen species. To combat against this oxidative induced free radical generation, many antioxidant compounds have been explored. In the present study, the antioxidant potential of traditional herb, Pergularia daemia (PD) was explored by invitro and invivo methods. The invitro analysis was done by determining the total antioxidant capacity, DPPH, superoxide and hydrogen peroxide scavenging activity and ferric reducing antioxidant capacity using spectrophotometry. Invivo study was done by pre-treating wistar strain albino rats with ethanolic extract of PD and exposing them to acute noise stress using a pure tone noise from a function generator for 45 min for 1 day. The discrete brain regions were dissected and the brain enzymatic and non-enzymatic antioxidant enzymes like superoxide dismutase, catalase, glutathione peroxidase, reduced glutathione, vitamin C and lipid peroxidation were analyzed. Results of invitro analysis revealed that PD extract exhibited a potent antioxidant capacity, scavenged the DPPH, superoxide and hydrogen peroxide and reduced the ferric ions to ferrous form in a dose dependent manner. Animals exposed to acute noise stress for 45 min showed a significant increase in plasma corticosterone and significantly increased the superoxide dismutase, catalase, glutathione peroxidase activity and lipid peroxidation in cerebral cortex, striatum, hippocampus and hypothalamus and decreased the reduced glutathione and vitamin C levels in all the four discrete regions of the brain. PD treatment significantly prevented those acute noise stress induced changes and restored it to normal.

Suppression and inhibition of Acetylcholinesterase (AChE) Gene Expression and Adenosine Deaminase (ADA) respectively in Cadmium Treated Rats by curcumin administration

Curcumin, the main polyphenolic component of turmeric (Curcuma longa) rhizomes have been reported to exert anticholinesterase and cognitive enhancing potentials with limited information on their scientific basis and how they regulate gene expression.This study sought to evaluate the in vitro effect of curcumin on cerebral cortex acetylcholinesterase (AChE) activity, their mRNA gene expression level and adenosine deaminase (ADA) in cadmium (Cd)‐treated rats. Animals were divided into six groups (n=6): group 1 [(control) received saline/vehicle], group 2 [saline plus curcumin (25 mg/kg)], group 3 [saline plus curcumin (50 mg/kg)], group 4 [Cd (2.5 mg/kg) plus vehicle], group 5 [Cd (2.5 mg/kg) plus curcumin (25 mg/kg)] and group 6 [Cd (2.5 mg/kg) plus curcumin (50 mg/kg)] by oral gavage for 7 days. Acetylcholinesterase (AChE) and adenosine deaminase (ADA) activities were determined and AChE expression was analyzed out using real time polymerase chain reaction (RT‐qPCR).The results of this study revealed that ADA activity was increased in Cd‐poisoned rats, and curcumin co‐treatment reversed this effect comparable to the control. Also, it was observed that acute administration of Cd increased AChE activity and caused a significant (P<0.05) increase in AChE mRNA levels in whole cerebral cortex when compared to control group. However, co‐treatment with curcumin inhibited AChE activity and alters AChE mRNA levels when compared to Cd‐treated rats. Furthermore, Cd intoxication increased the level of lipid peroxidation in cerebral cortex with a concomitant decreased in functional sulfhydryl (−SH) group and nitric oxide (NO). However, the co‐treatment with curcumin at 25 and 50 mg/kg, respectively increased the non‐enzymatic antioxidant status and NO in cerebral cortex with a decreased in malondialdehyde (MDA) level.In conclusion, inhibition of AChE and ADA activities, suppression of AChE mRNA gene expression level in Cd exposed rats, as well as increased antioxidant status by curcumin in Cd‐induced memory dysfunction could suggest some possible mechanism of action for their cognitive enhancing properties, thus providing some biochemical and molecular evidence on the therapeutic effect of this turmeric‐derived compound in treating neurological disorders including Alzheimer's disease.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Evaluation of epigallocatechin gallate and epicatechin gallate effects on acrylamide-induced neurotoxicity in rats and cytotoxicity in PC 12 cells

The neurotoxicity of acrylamide (ACR) monomer occurs through different mechanisms such as oxidative stress. Epigallocatechin gallate (EGCG) and epicatechin gallate (ECG) are green tea catechins which are known as powerful antioxidants. In this study, we examined the possible protective effects of ECG and EGCG on ACR neurotoxicity in both in-vitro and in-vivo models. PC12 cells were exposed to different concentrations of ECG and EGCG. After 24 and 48 hours, ACR was added to the cells (IC50 = 4.85 mM) and cell viability was measured through MTT assay after 24 hours. Male Wistar rats were pretreated with ECG, EGCG (10, 20 and 40 mg/kg, i.p) and vitamin E (200 IU/kg i.p.) for 3 days. Afterwards they were treated with ACR (50 mg/kg, i.p.) for 11 days. After the treatment period, gait score examination was performed and molondialdehyde (MDA) and reduced glutathione (GSH) were measured in cerebral cortex. ACR reduced the cell viability in a concentration-dependent manner. Both ECG and EGCG (20 μM) showed inhibitory effects on ACR cytotoxicity. ACR significantly induced gait abnormalities, decreased GSH level and increased lipid peroxidation in cerebral cortex. ECG and EGCG (20 mg/kg) improved all ACR toxic effects. Although the food intake was increased in pretreated groups compared to the ACR-treated group, intensive weight loss was observed due to the green tea’s different weight loss mechanisms. ECG and EGCG inhibited the cytotoxicity of ACR in PC12 cells and increased GSH level and decreased lipid peroxidation in rat cerebral cortex.

Curcumin improves episodic memory in cadmium induced memory impairment through inhibition of acetylcholinesterase and adenosine deaminase activities in a rat model.

Curcumin, the main polyphenolic component of turmeric (Curcuma longa) rhizomes has been reported to exert cognitive enhancing potential with limited scientific basis. Hence, this study sought to evaluate the effect of curcumin on cerebral cortex acetylcholinesterase (AChE) and adenosine deaminase (ADA) activities in cadmium (Cd)-induced memory impairment in rats. Animals were divided into six groups (n=6): saline/vehicle, saline/curcumin 12.5mg/kg, saline/curcumin 25mg/kg, Cd/vehicle, Cd/curcumin 12.5mg/kg, and Cd/curcumin 25mg/kg. Rats received Cd (2.5mg/kg) and curcumin (12.5 and 25mg/kg, respectively) by gavage for 7days. The results of this study revealed that cerebral cortex AChE and ADA activities were increased in Cd-poisoned rats, and curcumin co-treatment reversed these activities to the control levels. Furthermore, Cd intoxication increased the level of lipid peroxidation in cerebral cortex with a concomitant decreased in functional sulfuhydryl (-SH) group and nitric oxide (NO), a potent neurotransmitter and neuromodulatory agent. However, the co-treatment with curcumin at 12.5 and 25mg/kg, respectively increased the non-enzymatic antioxidant status and NO in cerebral cortex with a decreased in malondialdehyde (MDA) level. Therefore, inhibition of AChE and ADA activities as well as increased antioxidant status by curcumin in Cd-induced memory dysfunction could suggest some possible mechanism of action for their cognitive enhancing properties.

Sciatic Nerve Transection Modulates Oxidative Parameters in Spinal and Supraspinal Regions

Neuropathic pain is a very common dysfunction caused by several types of nerve injury. This condition leads to a variety of pathological changes in central nervous system regions related to pain transmission. It has been demonstrated that nociception is modulated by reactive oxidative species and treatments with antioxidant compounds produce antinociceptive effects. Thus, the aim of the present study was to investigate oxidative parameters in spinal and supraspinal regions following sciatic nerve transection (SNT). In behavioral assessments, animals showed mechanical allodynia and a significant functional impairment following SNT, measured by von Frey hairs test and sciatic functional index, respectively. Superoxide dismutase activity was increased 3 and 7 days following SNT in cerebral cortex and brainstem. Catalase activity was also increased in cerebral cortex 3 days after SNT. Ascorbic acid levels were decreased 7 days in the spinal cord only in SNT group. We also showed an increase in lipid peroxidation in cerebral cortex and brainstem 3 days after surgery in SNT and sham groups. These results showed that supraspinal regions also exhibit changes in antioxidant activity after SNT and demonstrate an intricate relationship among antioxidant defenses in different regions of the neuro axis related to pain transmission.

Curcumin differentially regulates the expression of superoxide dismutase in cerebral cortex and cerebellum of l-thyroxine (T4)-induced hyperthyroid rat brain

The present investigation was aimed to elucidate the effect of curcumin on lipid peroxidation (LPx) and superoxide dismutase (SOD) in L-thyroxine (T4)-induced oxidative stress in cerebral cortex and cerebellum of rat brain. Elevated level of LPx in cerebral cortex declined to control level on supplementation of curcumin to T4-treated rats. On the other hand, unaltered LPx level in T4-treated rats showed a significantly decreased level of LPx on supplementation of curcumin. The increased activity of SOD and translated products of SOD1 and SOD2 in cerebral cortex of T4-treated rats was ameliorated on supplementation of curcumin. The decreased activity of SOD and protein expression of SOD1 in cerebellum of T4-treated rats were ameliorated on administration of curcumin. On the other hand, SOD2 expression was not influenced either by T4-treated or by curcumin supplementation to T4-treated rats. Results of the present investigation reveal that the regulation of expression of SOD by curcumin in different regions (cerebral cortex and cerebellum) of rat brain is different under hyperthyroidism.

In vitro Antioxidant Activity of Valeriana officinalis Against Different Neurotoxic Agents

Valeriana officinalis L. (Valerian) is widely used as a traditional medicine to improve the quality of sleep. Although V. officinalis have been well documented as promising pharmacological agent; the exact mechanisms by which this plant act is still unknown. Limited literature data have indicated that V. officinalis extracts can exhibit antioxidant properties against iron in hippocampal neurons in vitro. However, there is no data available about the possible antioxidant effect of V. officinalis against other pro-oxidants in brain. In the present study, the protective effect of V. officinalis on lipid peroxidation (LPO) induced by different pro-oxidant agents with neuropathological importance was examined. Ethanolic extract of valerian (0-60 microg/ml) was tested against quinolinic acid (QA); 3-nitropropionic acid; sodium nitroprusside; iron sulfate (FeSO4) and Fe2+/EDTA induced LPO in rat brain homogenates. The effect of V. officinalis in deoxyribose degradation and reactive oxygen species (ROS) production was also investigated. In brain homogenates, V. officinalis inhibited thiobarbituric acid reactive substances induced by all pro-oxidants tested in a concentration dependent manner. Similarly, V. officinalis caused a significant decrease on the LPO in cerebral cortex and in deoxyribose degradation. QA-induced ROS production in cortical slices was also significantly reduced by V. officinalis. Our results suggest that V. officinalis extract was effective in modulating LPO induced by different pro-oxidant agents. These data may imply that V. officinalis extract, functioning as antioxidant agent, can be beneficial for reducing insomnia complications linked to oxidative stress.

Neuroprotective effect of N-acetylcysteine in the development of diabetic encephalopathy in streptozotocin-induced diabetes

Diabetic encephalopathy is characterized by impaired cognitive functions that involve neuronal damage triggered by glucose driven oxidative stress. The objective of the present study was to determine whether N-acetylcysteine (NAC) supplementation ameliorates learning and memory deficits caused by hyperglycemia-induced oxidative stress in experimental diabetes. Male Wistar rats (200-250 g) were rendered diabetic by a single intraperitoneal injection of streptozotocin (50 mg/kg). Cognitive deficits were observed in diabetic animals assessed using elevated plus maze test after 8 weeks of induction of diabetes. Acetylcholinesterase activity, a marker of cholinergic function, was decreased by 15.6% in the cerebral cortex, 20.9% in cerebellum and 14.9% in brain stem of diabetic rats compared to control rats. There was an increase in lipid peroxidation in cerebral cortex (21.97%), cerebellum (20.4%) and brain stem (25.5%) of diabetic rats. This was accompanied by decrease in glutathione and total thiol content along with decrease in the activities of superoxide dismutase, catalase and glutathione reductase. However, glutathione peroxidase activity increased by 11.2%, 13.6% and 23.1% in cerebral cortex, cerebellum and brain stem respectively, while the activity of glutathione-s-transferase decreased only in cerebral cortex (21.7%). Supplementation with NAC (1.4 g/kg/day in drinking water) significantly attenuated cognitive deficits and oxidative stress in diabetic rats. Our results emphasize the involvement of increased oxidative stress in cognitive impairment in diabetic animals and point towards the potential beneficial role of NAC as an adjuvant therapy to conventional anti-hyperglycemic regimens for the prevention and treatment of diabetic encephalopathy.

Nitric oxide associated with iNOS expression inhibits acetylcholinesterase activity and induces memory impairment during acute hypobaric hypoxia

The mechanisms responsible for cholinergic dysfunction associated learning and memory impairment during hypoxia are not well-understood. However it is known that inflammatory mediators like inducible nitric oxide synthase (iNOS) hamper the functions of cholinergic neurons. In this present experiment we made an effort to study the iNOS expression mediated retrograde and anterograde memory impairment in Balb/c mice following acute hypobaric hypoxia (at an altitude of 23,000ft for 6h) using elevated plus maze and passive avoidance step-through tasks. Our results demonstrated that hypoxia transiently impairs the retrograde memory without affecting the anterograde memory functions, accompanied with a substantial rise in iNOS expression and nitric oxide levels in cerebral cortex on days 2 and 3 post hypoxia. Treatment with aminoguanidine (iNOS inhibitor ), resulted in down-regulation of the iNOS expression, attenuation of the surge of nitric oxide (NO) in cerebral cortex and reversal of retrograde memory impairment due to hypoxia. Moreover the reduced AChE activity and elevated lipid peroxidation in cerebral cortex were evident during post hypoxia re-oxygenation period, which was not observed in the hippocampus. Additionally, NO donor spermine NONOate could inhibit the AChE activity in brain homogenates in a concentration-dependent manner, which further substantiate that nitric oxide produced during post hypoxia re-oxygenation, primarily contributes to the observed inhibition of cortical AChE activity. Based on these experiments we hypothesize that the NO burst as a result of iNOS upregulation during hypoxia interrupts the memory consolidation by altering the cholinergic functions.

Inhibitory role ofAcorus calamusin ferric chloride–induced epileptogenesis in rat

The roots and rhizomes of Acorus calamus (Family: Araceae) have been used in the ancient systems of medicine for the treatment of various neurological disorders. Of the various methods used for inducing experimental epileptic models, the intracortical administration of ferric chloride (FeCl(3)) into sensorimotor cortex induces recurrent seizures and epileptic discharge similar to human post-traumatic epilepsy through the generation of free radicals. The present study focuses on the effect of Acorus calamus on the behavioral, electroencephalographic, and antioxidant changes in FeCl(3)-induced rat epileptogenesis. Topical administration of FeCl(3) (5 microL; 100 mM) into the sensorimotor cortex of rats showed an increase in the wet dog shake behavior, spike wave discharges together with an significant increase in antioxidant enzyme activity, such as superoxide dismutase and catalase, resulting in an increase in the level of lipid peroxidation in cerebral cortex. Pretreatment with Acorus calamus (200 mg/kg b.w., p.o. for 14 days) and also diazepam (DZ, 20 mg/kg b.w., i.p.) decreased the WDS behavior, spike wave discharges with single isolated positive waves, and a significant decrease in activity of superoxide dismutase and level of lipid peroxidation was observed in cerebral cortex with respect to those observed in FeCl(3)-induced epileptic group. Data presented in this study clearly show that Acorus calamus possesses the ability for preventing the development of FeCl(3)-induced epileptogenesis by modulating antioxidant enzymes, which in turn exhibit the potentiality of Acorus calamus to be developed as an effective anti-epileptic drug.

Oxidative damage and sensitivity to nociceptive stimulus and opioids in aging rats

Oxidative stress contributes to aging and may cause alterations in pain and analgesia. Knowledge about effects of oxidative stress on the opioid system is very limited. This project was designed to determine the relationship between age-related oxidative damage and opioid antinociception. Three age groups of male Fischer 344 rats were tested for pain sensitivity and responses to morphine and fentanyl using the hot plate method. Oxidative stress markers in various brain regions were measured. With advancing age, nociceptive threshold and antinociceptive effects of opioids decreased significantly. There was a significant negative correlation between morphine antinociception and protein oxidation in cortex, striatum, and midbrain (r2=0.73, 0.87, and 0.77, respectively), and lipid peroxidation in cerebral cortex, hippocampus, and striatum (r2=0.73, 0.61, and 0.71, respectively). Similar correlation was observed between oxidative stress markers and fentanyl antinociception. These findings demonstrate that the age-related increase in oxidative damage in brain is associated with a significant decrease in the antinociceptive effects of opioids.

(664): Oxidative stress and sensitivity to pain and opioids in rats

Oxidative stress plays an important role in aging and development of neurodegeneration. Aberrant pain associated with oxidative stress-induced neurodegenerative disorders is inadequately managed because the neurodegeneration-related changes in sensitivity to pain and opioids are poorly understood. The knowledge about effects of oxidative stress on the opioid system is very limited. We have demonstrated significant decrease in opioid receptor function in neuronal cell cultures exposed to oxidative stress. The goal of this project was to study the relationship between oxidative damage and sensitivity to pain and opioids in rats. Three age groups (3-6, 9-12, and 21-24 months) of male Fisher 344 rats were tested for pain threshold and responses to three doses of morphine or fentanyl using the hot plate method. Various brain regions were used to measure oxidative stress markers and opioid receptors protein levels. The baseline sensitivity to thermal nociceptive stimulus increased significantly with age. There was a significant age-dependent and dose-dependent decrease in the antinociceptive effects of morphine and fentanyl. Levels of oxidative stress markers were the highest in brain regions from the oldest group of rats. There was a significant negative correlation between morphine antinociception and protein oxidation in cortex, striatum, and midbrain (r = 0.73, 0.87, and 0.77, respectively), and lipid peroxidation in cerebral cortex and striatum (r = 0.73 and 0.71, respectively). The mu opioid receptor protein level in cerebral cortex was significantly lower in the oldest rats. The results from this research show that (1) at the advanced age, the sensitivity to pain is significantly increased and the antonociceptive effect of opioids significantly decreased, (2) oxidative stress is negatively correlated with the opioid-induced antinocoception, and (3) age-related changes in pain and analgesia may be due to oxidative stress-induced reduction in opioid receptors protein level. Supported by NIH-NIA AG022550. Oxidative stress plays an important role in aging and development of neurodegeneration. Aberrant pain associated with oxidative stress-induced neurodegenerative disorders is inadequately managed because the neurodegeneration-related changes in sensitivity to pain and opioids are poorly understood. The knowledge about effects of oxidative stress on the opioid system is very limited. We have demonstrated significant decrease in opioid receptor function in neuronal cell cultures exposed to oxidative stress. The goal of this project was to study the relationship between oxidative damage and sensitivity to pain and opioids in rats. Three age groups (3-6, 9-12, and 21-24 months) of male Fisher 344 rats were tested for pain threshold and responses to three doses of morphine or fentanyl using the hot plate method. Various brain regions were used to measure oxidative stress markers and opioid receptors protein levels. The baseline sensitivity to thermal nociceptive stimulus increased significantly with age. There was a significant age-dependent and dose-dependent decrease in the antinociceptive effects of morphine and fentanyl. Levels of oxidative stress markers were the highest in brain regions from the oldest group of rats. There was a significant negative correlation between morphine antinociception and protein oxidation in cortex, striatum, and midbrain (r = 0.73, 0.87, and 0.77, respectively), and lipid peroxidation in cerebral cortex and striatum (r = 0.73 and 0.71, respectively). The mu opioid receptor protein level in cerebral cortex was significantly lower in the oldest rats. The results from this research show that (1) at the advanced age, the sensitivity to pain is significantly increased and the antonociceptive effect of opioids significantly decreased, (2) oxidative stress is negatively correlated with the opioid-induced antinocoception, and (3) age-related changes in pain and analgesia may be due to oxidative stress-induced reduction in opioid receptors protein level. Supported by NIH-NIA AG022550.

The effect of Juglandis Semen extract on improvement of tBHT‐induced Na+‐pump inactivity in rabbit cerebral cortex

This study was undertaken to determine whether Juglandis Semen (JAS) extract exerts protective effect against oxidant-induced inhibition of Na+-pump activity in cerebral cortex. Na+-pump activity was estimated by measuring ouabain-sensitive oxygen consumption. The oxygen consumption significantly inhibited by 1 mM t-butylhydroperoxide (tBHP), which was prevented by addition of 2% JAS extract. The oxygen consumption was increased by an increase in Na+ concentration from 5 to 100 mM, K+ concentration from 0.5 to 10 mM, and Mg2+ concentration from 0.2 to 5 mM. These changes in ion concentrations did not affect the inhibitory effect of tBHP and protective action of JAS on oxygen consumption. tBHP (1 mM) produced a significant increase in lipid peroxidation in cerebral cortex, which was prevented by 2% JAS extraction. These results suggest that JAS exerts protective effect against tBHP-induced inhibition of Na+-pump activity in the cerebral cortex, probably through action as antioxidant. This work was supported by the Research Project on the Production of Bio-organs (No. 200508010801), Ministry of Agriculture and Forestry, Korea.

호도약침액(胡桃藥鍼液)이 가토(家兎) 뇌조직(腦組織)의 Na+-pump 활성(活性) 장애(障碍)에 미치는 영향(影響)

This study was undertaken to determine whether Juglandis Semen (JAS) extraction exerts protective effect against oxidant-induced inhibition of -pump activity in cerebral cortex. -pump activity was estimated by measuring ouabain-sensitive oxygen consumption. The oxygen consumption significantly inhibited by 1 mM t-butylhydroperoxide (tBHP), which was prevented by addition of 2% JAS extraction. The oxygen consumption was increased by an increase in concentration from 5 to 100mM, concentration from 0.5 to 10 mM, and concentration from 0.2 to 5 mM. These changes in ion concentrations did not affect the inhibitory effct of tBHP and protective action of JAS on oxygen consumption. tBHP(1mM) produced a significant increase in lipid peroxidation in cerebral cortex, which was prevented by 2% JAS extraction. These result suggest that JAS exerts protective effect against tBHP-induced inhibition of -pump activity in the cerebral cortex, this effect may be due to by an antioxidant action.

A comparative study on lipid peroxidation in cerebral cortex of stroke-prone spontaneously hypertensive and normotensive rats

1.1. Lipid peroxidation and membrane-related enzyme changes in the cerebral cortex of stroke-prone rats (SHRSP) and normotensive rats were examined at 5 and 20 weeks of age.2.2. In vivo formation of thiobarbituric acid-reactant substances was higher in SHRSP at 20 weeks of age and in vitro generation of free malondialdehyde was greater in SHRSP brains, both at 5 and 20 weeks of age, as compared with those in WKY.3.3. Membrane-associated enzymes such as Na/K-ATPase and 5'-nucleotidase activities were lower in 20-week-old SHRSP than in age-matched WKY.4.4. These results indicate how very prone the SHRSP brain is toward lipid peroxidation and subsequent membrane-related enzyme changes.