Specific Regions Of Rat Brain Research Articles

Intracisternally Injected L-Proline Activates Hypothalamic Supraoptic, but Not Paraventricular, Vasopressin-Expressing Neurons in Conscious Rats

When injected into specific rat brain regions, the neurotransmitter candidate L-proline produces various cardiovascular changes through ionotropic excitatory amino acid receptors. The present study used an immunohistochemical double-labeling approach to determine whether intracisternally injected L-proline in freely moving rats, which increases blood pressure, activates hypothalamic vasopressin-expressing neurons and ventral medullary tyrosine-hydroxylase- (TH-) containing neurons. Following injection of L-proline, the number of activated hypothalamic neurons that coexpressed vasopressin and c-Fos was much greater in the supraoptic nucleus (SON) than in the paraventricular nucleus (PVN) of rats with increased blood pressure. The number of activated TH-containing neurons was significantly greater following L-proline treatment than following control injections of artificial cerebrospinal fluid (ACSF). These results clearly demonstrate that intracisternally injected L-proline activates hypothalamic supraoptic, but not paraventricular, vasopressin-expressing neurons and medullary TH-containing (A1/C1) neurons in freely moving rats.

Molecular Imaging of Brain Lipid Environment of Lymphocytes in Amyotrophic Lateral Sclerosis Using Magnetic Resonance Imaging and SECARS Microscopy

This paper highlights some of the key technologies of using two innovative molecular imaging modalites, magnetic resonance imaging (MRI) and nonlinear optical microscopy, for imaging intravenously injected ultra small paramagnetic iron oxide nanoparticles cross linked with antibodies (CLUSPIO) in the amyotrophic lateral sclerosis (ALS) experimental model in vivo or ex vivo, respectively. Intensive efforts have been made in investigating the causes of abnormalities in lipid metabolism, monitored in some neurodegenerative disorders systems. It has been shown that an abnormal accumulation of some common lipids in motor nerve cells may play a critical role in the development of amyotrophic lateral sclerosis. The presented experiments were performed on brain specimens from the transgenic rat model expressing multiple copies of mutated (G93A) human SOD-1 gene, after CD4+ lymphocytes were magnetically labeled with i.v.i. CLUSPIO antibodies. In vivo MRI revealed marked signal intensity enhancements in specific pathological regions of the ALS rat brain as compared to the wild type. Surface-enhanced coherent anti-Stokes Raman scattering (SECARS) microscopy indicated cellular interactions based on lipids association to anti-CD4 CLUSPIO.

Phase Advance of the Light-Dark Cycle Perturbs Diurnal Rhythms of Brain-derived Neurotrophic Factor and Neurotrophin-3 Protein Levels, Which Reduces Synaptophysin-positive Presynaptic Terminals in the Cortex of Juvenile Rats

In adult rat brains, brain-derived neurotrophic factor (BDNF) rhythmically oscillates according to the light-dark cycle and exhibits unique functions in particular brain regions. However, little is known of this subject in juvenile rats. Here, we examined diurnal variation in BDNF and neurotrophin-3 (NT-3) levels in 14-day-old rats. BDNF levels were high in the dark phase and low in the light phase in a majority of brain regions. In contrast, NT-3 levels demonstrated an inverse phase relationship that was limited to the cerebral neocortex, including the visual cortex, and was most prominent on postnatal day 14. An 8-h phase advance of the light-dark cycle and sleep deprivation induced an increase in BDNF levels and a decrease in NT-3 levels in the neocortex, and the former treatment reduced synaptophysin expression and the numbers of synaptophysin-positive presynaptic terminals in cortical layer IV and caused abnormal BDNF and NT-3 rhythms 1 week after treatment. A similar reduction of synaptophysin expression was observed in the cortices of Bdnf gene-deficient mice and Ca(2+)-dependent activator protein for secretion 2 gene-deficient mice with abnormal free-running rhythm and autistic-like phenotypes. In the latter mice, no diurnal variation in BDNF levels was observed. These results indicate that regular rhythms of BDNF and NT-3 are essential for correct cortical network formation in juvenile rodents.

The glutaminergic, GABAergic, dopaminergic but not cholinergic neurons are susceptible to anaesthesia-induced cell death in the rat developing brain

Neuronal cell death induced by anaesthetics in the developing brain was evident in previous pre-clinical studies. However, the neuronal cell types involved in anaesthesia-induced neuronal cell death remains elusive. The aim of this study was to investigate glutamatergic, GABAergic, cholinergic and dopaminergic neuronal cell apoptosis induced by anaesthetic exposure in specific brain regions in rats. Separate cohorts of 7-day-old Sprague Dawley (SD) rat pups were randomly assigned to two groups: Naive and anaesthetics alone (70% nitrous oxide and 0.75% isoflurane exposure for 6 h). The brains were sectioned and the slices that contained the basal forebrain, substantia nigra, cornu ammonis area 1 (CA1) subarea of hippocampus or cingulate cortex were selected and subsequently subjected to double-labelled fluorescent immunohistochemistry for choline acetyltransferase, dopamine, vesicular glutamate transporter 1 (vGLUT1) or glutamic acid decarboxylase 67 (GAD67) together with caspase 3, respectively. Compared to the naive control, anaesthetic exposure significantly increased the number of caspase-3 positive cells in the CA1 subarea of hippocampus, cingulate cortex, and substantia nigra, but not in the basal forebrain. 54% and 14% of apoptotic cells in the CA1 subarea of hippocampus were GABAergic and glutamatergic neurons respectively. In the cingulate cortex, 30% and 37% of apoptotic cells were GABAergic and glutamatergic neurons respectively. In the substantia nigra, 22% of apoptotic cells were dopaminergic neurons. Our data suggests, anaesthetic exposure significantly increases neuroapoptosis of glutamatergic, GABAergic and dopaminergic neurons in the developing brain but not that of the cholinergic neurons in the basal forebrain.

Phencyclidine (PCP)-Induced Disruption in Cognitive Performance is Gender-Specific and Associated with a Reduction in Brain-Derived Neurotrophic Factor (BDNF) in Specific Regions of the Female Rat Brain

Phencyclidine (PCP), used to mimic certain aspects of schizophrenia, induces sexually dimorphic, cognitive deficits in rats. In this study, the effects of sub-chronic PCP on expression of brain-derived neurotrophic factor (BDNF), a neurotrophic factor implicated in the pathogenesis of schizophrenia, have been evaluated in male and female rats. Male and female hooded-Lister rats received vehicle or PCP (n = 8 per group; 2 mg/kg i.p. twice daily for 7 days) and were tested in the attentional set shifting task prior to being sacrificed (6 weeks post-treatment). Levels of BDNF mRNA were measured in specific brain regions using in situ hybridisation. Male rats were less sensitive to PCP-induced deficits in the extra-dimensional shift stage of the attentional set shifting task compared to female rats. Quantitative analysis of brain regions demonstrated reduced BDNF levels in the medial prefrontal cortex (p < 0.05), motor cortex (p < 0.01), orbital cortex (p < 0.01), olfactory bulb (p < 0.05), retrosplenial cortex (p < 0.001), frontal cortex (p < 0.01), parietal cortex (p < 0.01), CA1 (p < 0.05) and polymorphic layer of dentate gyrus (p < 0.05) of the hippocampus and the central (p < 0.01), lateral (p < 0.05) and basolateral (p < 0.05) regions of the amygdaloid nucleus in female PCP-treated rats compared with controls. In contrast, BDNF was significantly reduced only in the orbital cortex and central amygdaloid region of male rats (p < 0.05). Results suggest that blockade of NMDA receptors by sub-chronic PCP administration has a long-lasting down-regulatory effect on BDNF mRNA expression in the female rat brain which may underlie some of the behavioural deficits observed post PCP administration.

Ethanol‐Induced Increase of Agouti‐Related Protein (AgRP) Immunoreactivity in the Arcuate Nucleus of the Hypothalamus of C57BL/6J, but not 129/SvJ, Inbred Mice

The melanocortin (MC) system is composed of peptides that are cleaved from the polypeptide precursor, pro-opiomelanocortin (POMC). Previous research has shown that MC receptor (MCR) agonists reduce, and MCR antagonists increase, ethanol consumption in rats and mice. Consistently, genetic deletion of the endogenous MCR antagonist, agouti-related protein (AgRP), causes reductions of ethanol-reinforced lever pressing and binge-like ethanol drinking in C57BL/6J mice. Ethanol also has direct effects on the central MC system, as chronic exposure to an ethanol-containing diet causes significant reductions of alpha-melanocyte stimulating hormone (alpha-MSH) immunoreactivity in specific brain regions of Sprague-Dawley rats. Together, these observations suggest that the central MC system modulates neurobiological responses to ethanol. To further characterize the role of the MC system in responses to ethanol, here we compared AgRP and alpha-MSH immunoreactivity in response to an acute injection of saline or ethanol between high ethanol drinking C57BL/6J mice and moderate ethanol drinking 129/SvJ mice. Mice received an intraperitoneal (i.p.) injection of ethanol (1.5 g/kg or 3.5 g/kg; mixed in 0.9% saline) or an equivolume of 0.9% saline. Two hours after injection, animals were sacrificed and their brains were processed for AgRP and alpha-MSH immunoreactivity. Results indicated that acute ethanol administration triggered a dose-dependent increase in AgRP immunoreactivity in the arcuate (ARC) of C57BL/6J mice, an effect that was not evident in the 129/SvJ strain. Although acute administration of ethanol did not influence alpha-MSH immunoreactivity, C57BL/6J mice had significantly greater overall alpha-MSH immunoreactivity in the ARC, dorsomedial, and lateral regions of the hypothalamus relative to the 129/SvJ strain. In contrast, C57BL/6J mice displayed significantly lower alpha-MSH immunoreactivity in the medial amygdala. The results show that acute ethanol exposure has direct effects on endogenous AgRP activity in ethanol preferring C57BL/6J mice. It is suggested that ethanol-induced increases in AgRP may be part of a positive feedback system that stimulates excessive binge-like ethanol drinking in C57BL/6J mice. Inherent differences in alpha-MSH immunoreactivity may contribute to differences in neurobiological responses to ethanol that are characteristically observed between the C57BL/6J and 129/SvJ inbred strains of mice.

S33-03 - Involvement of cytoskeletal microtubules in the action of antidepressant drugs

Growing evidence suggests that alterations in cytoskeletal microtubules dynamics may be involved in the effects of antidepressant drugs on brain structural neuronal plasticity phenomena such as remodelling of axons and dendrites. The speaker will review the most recent data in the field obtained in either naïve animals or in animal models of stress/depression. These results were gathered using a multidisciplinary approach, ranging from behavioural tests to neurochemistry and molecular analyses of specific markers of microtubule dynamics and synaptic remodelling. Several classes of antidepressant drugs have been shown to differentially modulate the expression of microtubular proteins and synaptic markers in specific rat brain regions depending from the dose and length of administration. Importantly, such antidepressant-induced effects on microtubular and synaptic proteins showed a very different pattern of changes in environmental (social isolation from weaning) or genetic (Flinders Sensitive Line) rat models of depression, which were not always accompanied by recover of the “depressive-like” behavioural phenotypes. Therefore, antidepressant drugs can modulate brain cytoskeletal and synaptic remodelling, but the pattern of these phenomena seems related to a complex gene-environment interaction. These data may be considered of translational human relevance when put in the context of partial- or non responders to antidepressant therapy. Finally, MAPREG developed new molecules specifically targeting neuronal microtubules and promoting structural neuronal plasticity, which may represent novel tools for the therapy of depressive disorders. Novel data on the antidepressant efficacy of one of these promising molecules in rat models of depression will be presented.

Fluoxetine administration modulates the cytoskeletal microtubular system in the rat hippocampus

A number of studies suggest that stressful conditions can induce structural alterations in the hippocampus and that antidepressant drugs may prevent such deficits. In particular, the selective serotonin reuptake inhibitor (SSRI) fluoxetine was more effective in modulating different neuronal plasticity phenomena and related molecules in rat hippocampus. Cytoskeletal microtubule dynamics are fundamental to dendrites and axons remodeling, leading to the hypothesis that fluoxetine may affect the microtubular system. However, despite reports of stress-induced alterations in microtubule dynamics by different stressors, only few studies investigated the in vivo effects of antidepressants on microtubules in specific rat brain regions. The present study investigated the dose-related (1, 5, or 10 mg/kg i.p.) effects of acute and chronic (21 days) treatments with fluoxetine on the ratio of hippocampal alpha-tubulin isoforms which is thought to reflect microtubule dynamics. Western Blot analysis was used to quantify alpha-tubulin isoforms, high-performance liquid chromatography and fluorescence detection was used to measure ex vivo monoamine metabolism. The results showed that acute fluoxetine increased the stable forms acetylated and detyrosinated alpha-tubulin. Conversely, chronic fluoxetine decreased acetylated alpha-tubulin, indicative of increased microtubule dynamics. The neuron-specific Delta2-Tubulin was increased by chronic fluoxetine indicating neuronal involvement in the observed cytoskeletal changes. Although acute and chronic fluoxetine similarly altered serotonin metabolism by inhibition of serotonin reuptake, this showed no apparent correlation to the cytoskeletal perturbations. Our findings demonstrate that fluoxetine administration modulates microtubule dynamics in rat hippocampus. The cytoskeletal effect exerted by fluoxetine may eventually culminate in promoting events of structural neuronal remodeling.

Fluoxetine inhibits corticotropin-releasing factor (CRF)-induced behavioural responses in rats

Corticotropin-releasing factor (CRF) is a potent neuromodulator of stress-related behaviour but the neural mechanisms underlying these effects are not clear. Studies were designed to test the hypothesis that CRF-induced behavioural arousal involves interactions with brainstem serotonergic systems. To examine interactions between CRF and serotonergic systems in the regulation of behaviour, CRF (1 μg, intracerebroventricular (i.c.v.)) or vehicle was infused in the presence or absence of the selective serotonin re-uptake inhibitor fluoxetine (0, 0.1, 1 or 10 mg/kg, intravenous (i.v.)). Fluoxetine was used at these doses because it is known to decrease serotonin cell firing rates while increasing extracellular serotonin concentrations in select forebrain regions. We then measured behavioural, neurochemical and endocrine responses. CRF increased locomotion and spontaneous non-ambulatory motor activity (SNAMA) in the home cages. Fluoxetine decreased tissue 5-hydroxyindoleacetic acid concentrations, a measure of serotonin metabolism, in specific limbic brain regions of CRF-treated rats (nucleus accumbens shell region, entorhinal cortex, central nucleus of the amygdala). Furthermore, fluoxetine inhibited CRF-induced SNAMA. CRF and fluoxetine independently increased plasma corticosterone concentrations, but the responses had distinct temporal profiles. Overall, these data are consistent with the hypothesis that CRF-induced facilitation of behavioural activity is dependent on brainstem serotonergic systems. Therefore, fluoxetine may attenuate or alleviate some behavioural responses to stress by interfering with CRF-induced responses.

Nimodipine prior to alcohol withdrawal prevents memory deficits during the abstinence phase

Effects of the dihydropyridine, nimodipine, an antagonist at L-type calcium channels, on the memory loss in rats caused by long term alcohol consumption were examined. Either a single dose of nimodipine or 2 weeks of repeated administration was given prior to withdrawal from 8 months of alcohol consumption. Memory was measured by the object recognition test and the T maze. Both nimodipine treatments prevented the memory deficits when these were measured between 1 and 2 months after alcohol withdrawal. At the end of the memory testing, 2 months after cessation of chronic alcohol consumption, glucocorticoid concentrations were increased in specific regions of rat brain without changes in plasma concentrations. Both nimodipine treatment schedules substantially reduced these rises in brain glucocorticoid. The data indicate that blockade of L-type calcium channels prior to alcohol withdrawal protects against the memory deficits caused by prolonged alcohol intake. This shows that specific drug treatments, such as nimodipine, given over the acute withdrawal phase, can prevented the neuronal changes responsible for subsequent adverse effects of long term consumption of alcohol. The results also suggest the possibility that regional brain glucocorticoid increases may be involved in the adverse effects of long term alcohol intake on memory. Such local changes in brain glucocorticoid levels would have major effects on neuronal function. The studies indicate that L-type calcium channels and brain glucocorticoid levels could form new targets for the treatment of cognitive deficits in alcoholics.

MicroPET Detection of Regional Brain Activation Induced by Colonic Distention in a Rat Model of Visceral Hypersensitivity

Using microPET and (18)F-fluorodeoxyglucose ((18)F-FDG) as a tracer, we investigated regional brain activation in a rat model of visceral hypersensitivity induced by 2,4,6-trinitrobenzene sulfonic acid (TNBS). TNBS injection into the proximal colon through laparotomy resulted in a significant, sustained decrease in the pain threshold to mechanical distention of the distal colon, indicating a phenomenon referred to as visceral hypersensitivity. When TNBS-induced colonic hypersensitivity was fully developed, all the TNBS-treated rats presented characteristic pain behaviors in response to colonic distention at previously innocuous pressure (0-35 mmHg) that produced no abdominal pain in sham-operated control animals. In microPET study, colonic distention at the normally non-painful pressure produced significant increases in (18)F-FDG uptake in the thalamus and sensory cortex I of TNBS-treated rats. Since the increases in (18)F-FDG uptake in the brain regions were completely abolished by an analgesic dose of morphine (375 microg/kg, s.c.), it is most likely that the regional brain activation detected by microPET is a pain-related central event. The pharmacological and microPET data indicate that colonic distention at the normally non-painful pressure activates specific brain regions in rats with TNBS-induced visceral hypersensitivity, and the microPET protocol described here could provide an objective measure to test visceral analgesic compounds.

EFFECT OF PERINATAL IRON DEFICIENCY ON BEHAVIORAL DEVELOPMENTS AND MYELINATION AROUND THE HIPPOCAMPUS IN RATS

INTRODUCTION: Iron deficiency is a common nutritional disorder. The effect of iron deficiency on myelination of specific brain regions and their relevant behavior has not been well documented. OBJECTIVE: The objective of this study was to determine the consequences of perinatal iron deficiency on behavioral and myelination of specific brain regions in rats. METHODS: Sixteen dams were randomly assigned to iron-sufficient or low-iron diets during gestation and lactation. Thereafter, all offspring were fed the iron-sufficient diet and were assessed for behavioral and neurologic developments. Behavioral assessments included sensorimotor function tests, a recognition memory task, and a spatial learning task. The density of myelination around the hippocampus was measured by 2`,3`-cyclic nucleotide 3`-phosphohydrolase (marker of oligodendrocyte) by means of immunohistochemistry and quantified by analysis of integrated optical density. The regions of interest included the corpus callosum and the fimbria of the hippocampus. RESULTS: Iron-deficient rats showed behavioral impairments in sensorimotor functions and recognition memory task but no significant differences were found in the spatial learning task. Iron-deficient rats had significantly reduced density of myelination than control rats in the corpus callosum but had no difference in the fimbria of the hippocampus. CONCLUSIONS: This study shows that perinatal iron deficiency can significantly alter the behavioral outcomes in rat pups and can profoundly influence the development of myelination in specific brain regions.

Specific brain regions of female rats are differentially depleted of docosahexaenoic acid by reproductive activity and an (n-3) fatty acid-deficient diet.

Low tissue levels of (n-3) PUFA, particularly docosahexaenoic acid [DHA, 22:6(n-3)], are implicated in postpartum depression. Brain DHA content is depleted in female rats undergoing pregnancy and lactation when the diet supplies inadequate (n-3) PUFA. In this study, the effects of DHA depletion as a result of reproductive activity and an (n-3) PUFA-deficient diet were examined in 8 specific brain regions of female rats after undergoing 2 sequential reproductive cycles. Virgin females, fed the alpha-linolenic acid (ALA)-containing or deficient (low-ALA) diets for a commensurate duration (13 wk) served as a control for reproduction. Total phospholipid composition of each brain region was determined at weaning (postnatal d 21) by TLC/GC. The regional PUFA composition of ALA virgins was similar to that previously measured in male rats. All brain regions examined were affected by reproductive activity and/or the low-ALA diet; however, the magnitude of the loss of DHA and compensatory incorporation of docosapentaenoic acid [(n-6) DPA, 22:5(n-6)] varied among brain regions. In low-ALA parous dams, frontal cortex (77% of ALA virgin) and temporal lobe (83% of ALA virgin), regions involved in cognition and affect, were among those exhibiting the greatest depletion of DHA. Caudate-putamen also exhibited significant depletion of DHA (82% of ALA virgin), whereas only (n-6) DPA levels were altered in ventral striatum, hypothalamus, hippocampus, and cerebellum. This pattern of changes in regional DHA and (n-6) DPA content suggests that specific neuronal systems may be differentially affected by depletion of brain DHA in the postpartum organism.

Selective Oxidative Stress in Brain Areas of Neonate Rats Exposed to 2,4-Dichlorophenoxyacetic Acid Through Mother's Milk

2,4-Dichlorophenoxyacetic acid (2,4-D) induced disparate alterations on enzymatic activities of the defensive mechanism and/or modifications of the reactive oxygen species levels in specific neonate rat brain regions. The midbrain, striatum, and prefrontal cortex were the areas where the alterations were more remarkable and with similar tendency. The hippocampus did not suffer many alterations, and the hypothalamus was the area where no changes were observed. The current results suggest that the developing brain areas have different susceptibilities to the adverse effect of the herbicide, especially those areas related to the dopaminergic system, and that oxidative stress is one 2,4-D mechanism of toxicity.

Streptozotocin-induced diabetes progressively increases blood-brain barrier permeability in specific brain regions in rats

This study investigated the effects of streptozotocin-induced diabetes on the functional integrity of the blood-brain barrier in the rat at 7, 28, 56, and 90 days, using vascular space markers ranging in size from 342 to 65,000 Da. We also examined the effect of insulin treatment of diabetes on the formation and progression of cerebral microvascular damage and determined whether observed functional changes occurred globally throughout the brain or within specific brain regions. Results demonstrate that streptozotocin-induced diabetes produced a progressive increase in blood-brain barrier permeability to small molecules from 28 to 90 days and these changes in blood-brain barrier permeability were region specific, with the midbrain most susceptible to diabetes-induced microvascular damage. In addition, results showed that insulin treatment of diabetes attenuated blood-brain barrier disruption, especially during the first few weeks; however, as diabetes progressed, it was evident that microvascular damage occurred even when hyperglycemia was controlled. Overall, results of this study suggest that diabetes-induced perturbations to cerebral microvessels may disrupt homeostasis and contribute to long-term cognitive and functional deficits of the central nervous system.

The dam breaks: disruption of the blood-brain barrier in diabetes mellitus

AT THE END OF THE CENTURY before the last, a young graduate student performed an experiment that would forever change the way we look at the microvasculature of the brain. He injected basic dyes into the blood and noted that nearly every tissue of the body was colored by the dye except for the central nervous system (CNS). This experiment and the observation that bile salts could cause seizures when injected into the brain but not intravenously were the seminal 19th century observations giving rise to the concept of a blood-brain barrier (BBB). The young graduate student, Paul Ehrlich, would get many things right in his career, winning a Nobel prize in 1908 for his work on antibiotics. But the BBB he got wrong. Ehrlich thought the brain did not stain because the dye was not taken up by brain tissue, not because a barrier prevented the dye from reaching the brain. Indeed, that a BBB really existed and that it resided at the level of the capillary bed and the choroid plexus were not finally established until the late 1960s. Elegant physiological experiments by Davson and Segal (10) and electron microscopy studies by Reese and Karnovsky (24) demonstrated the basis of the BBB: the capillary bed of adult mammals is modified to exclude the production of a plasma ultrafiltrate. The major modifications include a greatly decreased rate of pinocytosis, a lack of intracellular pores and fenestrae, and obliteration of the intercellular space between brain endothelial cells by tight junctions that essentially “cement” apposing endothelial cells together. The lack of production of an ultrafiltrate means that circulating proteins such as albumin do not exude from blood into brain. This is the basis for Ehrlich’s 120-year-old observation: basic dyes bind to albumin so tightly that they are a visible proxy for plasma

Differential effects of modulation of docosahexaenoic acid content during development in specific regions of rat brain

Variation in brain FA composition, particularly decreased DHA (22:6n-3), affects neurodevelopment, altering visual, attentional, and cognitive functions, and is implicated in several neuropsychiatric disorders. To further understand how specific brain processes and systems are affected by variation in brain DHA content, we sought to determine whether specific brain regions were differentially affected by treatments that alter brain DHA content. Adult male Long-Evans rats were raised from conception using diet/breeding treatments to produce four groups with distinct brain phospholipid compositions. Total phospholipid FA composition was determined in whole brain and 15 brain regions by TLC/GC. Brain regions exhibited significantly different DHA contents, with the highest levels observed in the frontal cortex and the lowest in the substantia nigra/ventral tegmental area. Increased availability of DHA resulted in increased DHA content only in the olfactory bulb, parietal cortex, and substantia nigra/ventral tegmental area. In contrast, treatment that decreased whole-brain DHA levels decreased DHA content in all brain regions except the thalamus, dorsal midbrain, and the substantia nigra/ventral tegmental area. Alterations in DHA level were accompanied by changes in docosapentaenoic acid (n-6 DPA, 22:5n-6) content; however, the change in DHA and n-6 DPA was nonreciprocal in some brain regions. These findings demonstrate that the FA compositions of specific brain regions are differentially affected by variation in DHA availability during development. These differential effects may contribute to the specific neurochemical and behavioral effects observed in animals with variation in brain DHA content.

Methylphenidate treatment induces oxidative stress in young rat brain

Methylphenidate (MPH) is frequently prescribed for the treatment of attention deficit/hyperactivity disorder. Psychostimulants can cause long-lasting neurochemical and behavioral adaptations. Here, we evaluated oxidative damage in the rat brain and the differential age-dependent response to MPH after acute and chronic exposure. We investigated the oxidative damage, assessed by the thiobarbituric acid reactive species (TBARS), and the protein carbonyl assays in cerebellum, prefrontal cortex, hippocampus, striatum, and cerebral cortex of young (25 days old) and adult (60 days old) male Wistar rats after acute and chronic exposure to MPH. Chronic MPH-treated young rats presented a dose-dependent increase in TBARS content and protein carbonyls formation in specific rat brain regions. In the acute exposure, only MPH highest dose increased lipid peroxidation in the hippocampus. No difference in protein carbonilation was observed among groups in all structures analyzed. In adult rats, we did not find oxidative damage in both acute and chronic treatment. Chronic exposure to MPH in induces oxidative damage in young rat brain, differentially from chronic exposure during adulthood. These findings highlight the need for further research to improve understanding of MPH effects on developing nervous system and the potential consequences in adulthood resulting from early-life drug exposure.

Neuropsychological Disorders Indicative of Postresuscitation Encephalopathy in Rats

The aim of this research was to study the effect of 12-minute clinical death on innate and acquired behavior, biogenic amine concentration, and the composition and quantity of neural populations in specific brain regions of white rats. The study shows that in animals during the postresuscitation period with formal restoration of neurological status, there are changes in emotional reactivity, orientation-exploration reactions, impairment of learning and memory, decrease in exercise tolerance and pain sensitivity. These processes are accompanied by alterations in serotonin and norepinephrine levels in the frontal cerebral cortex, dopamine and serotonin levels in the striatum, certain biochemical indices in blood plasma and neural loss in the CA1 sector of the hippocampus and lateral portions of the cerebellum.

Morphometric studies of specific brain regions of rats chronically intoxicated with the organophosphate methamidophos

Subtle neurological disturbances have been described in organophosphorus intoxication. Experimental studies have reported neuronal necrosis, particularly in animals experiencing seizures. The objective of the present work was to investigate if in rats (without seizures) exposed to an organophosphate agent, morphological changes occur in specific regions of the brain. The animals received 2.5 or 5.0 mg/kg methamidophos once a week for 2 months and were decapitated after 2 months 7 days of drug administration. We observed atrophy of the molecular layer of the parietal cortex without neuronal loss in specific cerebral regions. This would be due to atrophy or loss of neuronal ramifications but without neuronal loss.