Young Rat Brain Research Articles

Regional rat brain distribution of heme oxygenase-1 and manganese superoxide dismutase mRNA: relevance of redox homeostasis in the aging processes.

Increasing evidence supports the notion that reduction of cellular expression and activity of antioxidant proteins and the resulting increase of oxidative stress are fundamental causes in the aging processes and neurodegenerative diseases. In the present study, we evaluated, in the brains of young and aged rats, the gene expression profiles of two inducible proteins critically involved in the cellular defense against endogenous or exogenous oxidants: heme oxygenase-1 (HO-1) and manganese superoxide dismutase-2 (SOD-2). SOD-2 is an essential antioxidant and HO-1 has been reported to be very active in regulating cellular redox homeostasis. Deregulation of these enzymes has been extensively reported to play a crucial role in the pathogenesis of neurodegenerative disorders. To measure the regional distribution of HO-1 and SOD-2 transcript levels in the rat brain, we have developed a real time quantitative reverse transcription-polymerase chain reaction protocol. Although these two genes presented a highly dissimilar range of expression, with SOD-2 >HO-1, both transcripts were highly expressed in the cerebellum and the hippocampus, showing in a different scale a strikingly parallel distribution gradient. To further investigate the regional brain expression of these mRNAs, we performed in situ hybridization using specific riboprobes. In situ hybridization results showed that both transcripts were highly concentrated in the hippocampus, the cerebellum and some specific regions of the brain cortex. We have also quantified, by reverse transcription-polymerase chain reaction, the brain expression of HO-1 and SOD-2 mRNAs in middle aged (12 months) and aged (28 months) rats. We found that the hippocampus of aged rats presents a significant down regulation of SOD2 mRNA expression and a parallel upregulation of HO-1 mRNA compared with young (6 months) and middle-aged rats. Furthermore, in the cerebellum of the aged rats, we detected a parallel significant upregulation of both HO-1 and SOD-2 transcripts. These regional age-dependent differences may help to explain the increased susceptibility to oxidative damage in these two brain areas during aging.

Age-related oxidative inactivation of Na +, K +-ATPase in rat brain crude synaptosomes

The study was undertaken to examine the status of Na +, K +-ATPase in aged rat brain and to verify if any alteration of this enzyme in aged brain could be related to an oxidative damage. The crude synaptosomes from rat brain were exposed in vitro to an oxidative stress in the form of a combination of Fe 2+ (100 μM) and ascorbate (2 mM) for up to 2 h when increased lipid peroxidation (nearly four-fold), extensive protein carbonyl formation and a marked decrease of Na +, K +-ATPase activity (approximately 88%) were observed. All these changes were prevented by the presence of a chain-breaking anti-oxidant, butylated hydroxytoluene (0.2 mM), in the incubation mixture. When the same crude synaptosomal membranes from the young (4–6 months) and aged (18–22 months) rat brains were analysed, a significant reduction of Na +, K +-ATPase activity (nearly 48%) along with significantly elevated levels of lipid peroxidation products and protein carbonyls could be detected in the aged animals in comparison to young ones. The latter data in combination with the results of in vitro experiments imply that the age-related decline of rat brain Na +, K +-ATPase activity is presumably the consequence of an enhanced oxidative damage in aging brain

Effects of age and dexamethasone treatment on glucocorticoid response element and activating protein-1 binding activity in rat brain.

The effect of dexamethasone (DEX) on glucocorticoid receptor (GR)-mediated gene expression was examined in the brain of young and aged rats. Electrophoretic mobility shift assays showed that DEX treatment led to an increase of glucocorticoid response element (GRE) binding activity in aged rats, whereas in young animals GRE binding activity was decreased. Western blot analysis and reverse transcriptase polymerase chain reaction confirmed that, in aged animals, the GR mRNA and the GR protein levels were increased on DEX treatment. The binding activity of GRE activating protein-1 (AP-1) site and cross-competition analysis demonstrated specific pattern of expression during the ageing and DEX treatment, suggesting that GR modulates the activity of transcription factors AP-1 (Fos/Jun proteins) through protein-protein interaction. On the basis of these results, it can be concluded that the composition of transcriptional complexes that bind to GRE and AP-1 regulatory elements changes upon DEX treatment in an age-specific manner.

Glutaric acid induces oxidative stress in brain of young rats

This study investigated the effects of glutaric acid, which predominantly accumulates in glutaric acidemia type I, on some in vitro parameters of oxidative stress in brain of young rats. We evaluated chemiluminescence, total radical–antioxidant potential (TRAP) and the activities of the antioxidant enzymes catalase, glutathione peroxidase and superoxide dismutase in brain tissue homogenates in the presence of glutaric acid at concentrations ranging from 0.05 to 2.0 mM. The acid significantly increased chemiluminescence (up to 65%) and reduced total radical–antioxidant potential (up to 28%) and glutathione peroxidase activity (up to 46%), without affecting catalase and superoxide dismutase activities. The results provide evidence that glutaric acid induces oxidative stress in vitro in rat brain. If these findings also occur in humans, it is possible that they may contribute to the neuropathology of patients affected by glutaric acidemia type I.

Developmental Pb 2+ exposure alters NMDAR subtypes and reduces CREB phosphorylation in the rat brain

In the present study we show that chronic exposure to low levels of lead (Pb 2+) during development alters the type of N-methyl- d-aspartate receptor (NMDAR) expressed in the developing and young adult rat brain. Ifenprodil inhibition of [ 3H]MK-801 binding to the NMDAR channel in cortical and hippocampal neuronal membranes expressed high and low affinity components. Previous studies have shown that the high affinity component is associated with NR1/NR2B receptor complexes while the low affinity component is associated with the appearance and insertion of the NR2A subunit to NMDAR complexes. Pb 2+-exposed rats express a greater number of [ 3H]MK-801 binding sites associated with the high affinity and low affinity components of ifenprodil inhibition. Further, [ 3H]ifenprodil saturation isotherms and Scatchard analysis in cortical and hippocampal membranes showed a higher number of binding sites ( B max) with no change in binding affinity ( K d) in Pb 2+-exposed animals relative to controls. Quantitative [ 3H]MK-801 autoradiography in response to glutamate and glycine provided evidence that NMDAR complexes in Pb 2+-exposed rat brain were maximally activated in situ. Higher levels of ifenprodil-sensitive binding sites and increased sensitivity to agonists are properties characteristic of NR1/NR2B recombinant receptors. Thus, our results strongly suggest that a greater proportion of the total number of NMDAR are NR1/NR2B receptors in the Pb 2+-exposed rat brain. This Pb 2+-induced change in NMDAR subtypes in the rat brain was associated with reduced CREB phosphorylation in cortical and hippocampal nuclear extracts. These findings demonstrate that chronic exposure to environmentally relevant levels of Pb 2+ altered the subunit composition of NMDAR complexes with subsequent effects on calcium-sensitive signaling pathways involved in CREB phosphorylation.

Age‐related decline in neurogenesis: Old cells or old environment?

Age‐related decline in neurogenesis: Old cells or old environment?

Ultrastructural analysis of the paranodal junction of myelinated fibers in 31-month-old-rats.

Recent studies have revealed a significant decrease in white matter volume, including loss of myelin, with age but minimal decrease in gray matter volume (Guttmann et al., [1998] Neurology 50:972-978). Myelin is necessary for the rapid conduction of impulses along axons. Myelinated nerve includes various domains, the node of Ranvier, the paranodal region, the juxtaparanodal region and the internode. The paranodal junction may serve to anchor the myelin sheath to the axon. We analyzed the ultrastructure of the paranodal region in myelinated fibers from the aged rat brain. Severe alterations of myelinated fibers were observed in 31-month-old rats, resulting in the appearance of macrophages, splitting of the myelin sheath, myelin balloon formation and separation from the axon. Many paranodal retractions of myelinated axons occurred in the aged rats. It should be noted that the paranodal junction is functionally important, serving to anchor the myelin to the axon and that there is a diffusion barrier in the paranodal region. We analyzed myelin-related proteins from young and aged rat brains. The 21.5-kDa isoform of myelin basic protein (MBP) almost disappeared in the 31-month-old rats, whereas other myelin proteins were not significantly changed between young and aged rats. These results suggest that this isoform, a highly cationic charged major dense component protein that binds lipid bilayer in the membrane, may participate in the formation of a paranodal diffusion barrier at the myelin/noncompact membrane border.

Age-related changes of the nitric oxide system in the rat brain

This work examines the age-related changes of the NO pathway in the central nervous system (CNS), analyzing nitric oxide synthase (NOS) isoform expression, the level of nitrotyrosine-modified proteins, and the NOS activity in the cerebral cortex, decorticated brain (basal ganglia, thalamus, hypothalamus, tegtum and tegmentum) and cerebellum of young, adult and aged rats. Our data demonstrate that the different NOS isoforms are not uniformly expressed across the CNS. In this sense, the nNOS and eNOS isoenzymes are expressed mainly in the cerebellum and decorticated brain, respectively, while the iNOS isoenzyme shows the highest level in cerebellum. Concerning age, in the cerebral cortex nNOS significantly increased its expression only in adult animals; meanwhile, in the cerebellum the eNOS expression decreased whereas iNOS increased in adult and aged rats. No age-related changes in any isoform were found in decorticated brain. NOS activity, determined by nitrate plus nitrite quantification, registered the highest levels in the cerebellum, where the significant increase detected with aging was probably related to iNOS activity. The number of nitrotyrosine-modified immunoreactive bands differed among regions; thus, the highest number was detected in the decorticated brain while the cerebellum showed the least number of bands. Finally, bulk protein nitration increased in cerebral cortex only in adult animal. No changes were found in the decorticated brain, and the decrease detected in the cerebellum of aged animals was not significant. According to these results, the NO pathway is differently modified with age in the three CNS regions analyzed.

Chronic treatments with tacrine and (-)-nicotine induce different changes of nicotinic and muscarinic acetylcholine receptors in the brain of aged rat.

The present study evaluated effects of chronic treatment with tacrine and (-)-nicotine for 21 days on nicotinic and muscarinic acetylcholine receptors in the brains of old rats (24-25 months) by receptor autoradiography. The nicotinic receptor (nAChR) binding sites were measured by (-)-[3H]nicotine and [3H]epibatidine, and the muscarinic receptor (mAChR) binding sites by [3H]pirenzepine and [3H]AFDX 384. No change in (-)-[3H]nicotine binding was observed in all of the brain regions analysed following chroinic treatment with tacrine (10 mg/kg). Similarly, the [3H]epibatidine binding was not changed in most of the brain regions analysed except for a few brain regions where a decrease was observed in tacrine treated animals compared to control animals. Chronic treatment with (-)-nicotine (0.45 mg base/kg) significantly increased both (-)-[3H]nicotine and [3H]epibatidine bindings in every brain regions analysed except for the hippocampus when measured by (-)-[3H]nicotine. A significant decrease in [3H]AFDX 384 binding, but not in [3H]pirenzepine binding was observed in all of the brain regions analysed following the treatment with tacrine. These data suggest that chronic treatments with tacrine and (-)-nicotine differentially interfere and regulate the subtypes of nAChRs and mAChRs in the brain of aged rat. These data differ from what have been earlier observed in the brain of young adult rat following tacrine treatment, revealing some dynamic changes in receptor properties in the brain during aging.

Age-associated mitochondrial oxidative decay: improvement of carnitine acetyltransferase substrate-binding affinity and activity in brain by feeding old rats acetyl-L- carnitine and/or R-alpha -lipoic acid.

We test whether the dysfunction with age of carnitine acetyltransferase (CAT), a key mitochondrial enzyme for fuel utilization, is due to decreased binding affinity for substrate and whether this substrate, fed to old rats, restores CAT activity. The kinetics of CAT were analyzed by using the brains of young and old rats and of old rats supplemented for 7 weeks with the CAT substrate acetyl-l-carnitine (ALCAR) and/or the mitochondrial antioxidant precursor R-alpha-lipoic acid (LA). Old rats, compared with young rats, showed a decrease in CAT activity and in CAT-binding affinity for both substrates, ALCAR and CoA. Feeding ALCAR or ALCAR plus LA to old rats significantly restored CAT-binding affinity for ALCAR and CoA, and CAT activity. To explore the underlying mechanism, lipid peroxidation and total iron and copper levels were assayed; all increased in old rats. Feeding old rats LA or LA plus ALCAR inhibited lipid peroxidation but did not decrease iron and copper levels. Ex vivo oxidation of young-rat brain with Fe(II) caused loss of CAT activity and binding affinity. In vitro oxidation of purified CAT with Fe(II) inactivated the enzyme but did not alter binding affinity. However, in vitro treatment of CAT with the lipid peroxidation products malondialdehyde or 4-hydroxy-nonenal caused a decrease in CAT-binding affinity and activity, thus mimicking age-related change. Preincubation of CAT with ALCAR or CoA prevented malondialdehyde-induced dysfunction. Thus, feeding old rats high levels of key mitochondrial metabolites can ameliorate oxidative damage, enzyme activity, substrate-binding affinity, and mitochondrial dysfunction.

Stimulation of lipid peroxidation in vitro in rat brain by the metabolites accumulating in maple syrup urine disease.

In this study we investigated the in vitro effects of the metabolites accumulating in maple syrup urine disease on lipid peroxidation in brain of young rats. Chemiluminescence and thiobarbituric acid-reactive substances were measured in brain homogenates from 7- and 30-day-old rats in the presence of 10 mM of the branched-chain amino acids L-leucine, L-isoleucine, or L-valine; their keto acids L-2-ketoisocaproic acid, L-2-keto-3-methylvaleric acid, or L-2-ketoisovaleric acid; or the hydroxy derivatives L-2-hydroxyisocaproic acid, L-2-hydroxy-3-methylvaleric acid, or L-2-hydroxyisovaleric acid separately added to the incubation medium. We observed that all amino acids, keto acids, and hydroxy acids accumulating in this disease stimulate to a variable degree the in vitro parameters of lipid peroxidation tested in homogenates of rat brain. The results indicate a possible participation of oxidative stress in the neuropathology of maple syrup urine disease patients, especially during a crisis, when the metabolites are highly increased, and point to the use of antioxidant drugs as a possible adjuvant therapy in such situations to improve the neurological status of the patients and to prevent sequelae.

Postnatal Handling Induces Long-term Modifications in Central β-noradrenergic Signalling in Rats

Neonatal handling has been shown to induce a short-term reduction in the binding properties of g -adrenoceptors and in their primary biochemical responses in the young rat brain, which may account for the reduced responsiveness to stress observed in the handled rats. We have studied the persistence and duration of these changes in cerebral cortex, cerebellum and hippocampus at successive stages of life in neonatally handled rats. Binding properties of the g -adrenoceptors in handled animals were essentially similar to those of the control rats from 3 to 24 months of age. However, handling disturbed the efficacy of the g -adrenoceptor intracellular signalling since the isoprenaline-induced accumulation of cyclic AMP was reduced in cerebral cortex at 1, 12 and 24 months; in cerebellum at 12 and 18 months; and in hippocampus at 3 and 12 months. This effect might be partially dependent on a regulatory action of handling on the adenylyl cyclase enzyme itself since both basal and forskolin-induced accumulation of cyclic AMP were persistently reduced. Therefore, postnatal handling can be considered as an effective intervention that modifies sensitivity to various hormonal and neurochemical signals; these changes may be involved over a long period of time in protection against an excessive response to stress. These results suggest that the long-lasting adaptation of the adenylyl cyclase transduction system, which affects the primary biochemical response of the g -adrenoceptor, may participate in the effects of this manipulation.

Kainic acid modifies mu-receptor binding in young, adult, and elderly rat brain.

Mu-receptor binding changes were evaluated following the kainic acid (KA)-induced status epilepticus (SE) in young, adult, and elderly animals. Male Wistar rats were used as follows: young rats (15 days old) were treated with KA (7 mg/kg) and sacrificed 72 h (YKA3d) or 35 days (YKA35d) after SE; adult (90 days old) (AKA1d and AKA40d) and elderly rats (1-year-old) (EKA1d and EKA40d) were injected with KA (10 mg/kg) and then sacrificed 24 h or 40 days following SE. Their brains were processed for an autoradiography assay for mu-receptors. The YKA3d group showed increased values in dentate gyrus (39%) and a decrease in substantia nigra (26%); YKA35d animals had a reduction in caudate putamen (29%) and in substantia nigra (20%). The AKA1d group exhibited increased mu-receptors in caudate putamen (49%), cingulate (415%), frontal (52%), and temporal (53%) cortices: substantia nigra (56%), dentate gyrus (48%). and CA2 field of hippocampus (53%). The AKA40d group showed increased values in sensorimotor cortex (45%), anterior (39%), medial (65%), basolateral (202%), and central (32%) amygdaloid nuclei; dentate gyrus (80%) as well as CA2 (80%) and CA3 (49%) fields of hippocampus. The EKA1d group presented decreased mu-receptor binding in piriform (16%) and enthorinal (22%) cortices as well as in anterior amygdala nucleus (17%). The EKA40d group showed reduced values in sensorimotor cortex (14%) and substantia nigra (27%). The present results indicate that the mu-binding changes following SE depend on the rate of brain maturation.

Ebb Tide: Brain center linked to decrease in egg-producing waves

As mammals age, one of the first things to go is reproductive capacity. Ovulation becomes irregular, because waves of luteinizing hormone (LH) don't crest as high as before. New results indicate that a reduction in nerve impulses from a particular part of the brain is partly responsible for lowering the levels of the hormone that triggers LH production. Release of luteinizing hormone-releasing hormone (LH-RH) from neurons in the hypothalamus, a part of the brain that governs a host of hormone-controlled bodily functions, spurs the pituitary gland to produce waves of LH. These so-called LH surges stimulate egg release from the ovaries, but they diminish during aging because production of LH-RH by hypothalamic neurons decreases. Exactly what causes this decline is unknown, but some suspect that neurons from elsewhere in the hypothalamus might be to blame. Previous work implicated a region known as the AVPv: AVPv nerve cells connect to LH-RH-producing neurons, and damaging the AVPv blocks LH surges. But it hasn't been clear if a decrease in AVPv activity with advancing years prevents LH-RH synthesis. In search of a missing link, Le and colleagues looked for activity in AVPv and LH-RH neurons in the brains of young and middle-aged rats sacrificed in the midst of an LH surge. The team used antibodies to detect the presence of the Fos protein, an indicator of neuron activity. A smaller percentage of LH-RH neurons in middle-aged rat brains contained Fos as compared with young rat brains. In addition, a similarly reduced fraction of neurons in the AVPv region of middle-aged brains lit up with Fos. The researchers then damaged AVPv in young rats and monitored LH-RH neuron activity. LH-RH neurons on the same side of the brain as the lesion took a hit, expressing no Fos; LH-RH neurons on the uninjured side of the brain carried on normally. The results add to evidence that nerves in the AVPv stimulate LH-RH production. They also suggest that reduced AVPv firing accounts in part for the waning LH-RH production--and, in turn, the declining LH and loss of ovulation--that comes with age. Why AVPv activity falls over time is unclear, and the answer is not likely to be simple. The AVPv takes in signals from multiple hormones and neurons, so the change probably involves more than one trigger. And other brain centers could play roles as well. Further elucidating this pathway will help researchers understand how once-swelling hormonal seas flatten. --R. John Davenport W.-W. Le, P. M. Wise, A. Z. Murphy, L. M. Coolen, G. E. Hoffman, Parallel declines in Fos activation of the medial anteroventral periventricular nucleus and LHRH neurons in middle-aged rats. Endocrinology 142 , 4976-4982 (2001). [Abstract] [Full Text]

Age-specific changes in expression, activity, and activation of the c-Jun NH 2-terminal kinase and p38 mitogen-activated protein kinases by methyl methanesulfonate in rats

The stress-activated protein kinases (SAPKs), c-Jun NH 2-terminal kinases (JNKs) and p38 mitogen-activated protein kinases, were evaluated in the liver and brain of young and old rats in response to a direct-acting alkylating agent, methyl methanesulfonate (MMS). A slight but statistically significant increase in the baseline expression levels of JNK isoforms was detected in both the liver and brain of old as compared with young rats. In the liver of both young and old rats, no basal activities of JNKs were detected. In the brain, JNK activities were constitutively high and significantly increased in old rats compared with their young counterparts. Upon MMS treatment, JNKs were strongly activated in the liver, but not in the brain, of both young and old animals. The basal activity of p38 significantly increased in both the liver and brain of old rats as compared with young rats. An increase in the basal expression of p38 was detected in the brain but not in the liver of old rats. Upon treatment with MMS, p38 was activated in the liver of both young and old rats. In the brain, p38 was only activated in young but not in old rats. Taken together, these results demonstrate age-specific as well as organ-specific SAPKs signaling pathways in the rat in vivo. The possible implications of these findings in terms of resistance to endogenous and environmentally induced genotoxic stress during aging are discussed.

Different expression of glycogen synthase kinase-3β between young and old rat brains after transient middle cerebral artery occlusion

Ischemia is a common stress to human brain and is difficult to cure in older individuals. To examine the differences of the response to cerebral ischemia between young and old rat brains, distributions of glycogen synthase kinase-3β (GSK3β) and tau proteins were analyzed after 90 min of transient middle cerebral artery occlusion (MCAO) in young (10-11 weeks) and old (15 months) rats by immunohistochemical analyses. At 4 h of reperfusion, strong cytoplasmic and nuclear immunoreactivity for GSK3β was induced in neurons of lamina I, II, V and VI of the cerebral cortex and dorsal caudate in young brains, while the induction was not observed in lamina I and II of old cerebral cortex. The staining in lamina V and VI and dorsal caudate then gradually decreased until seven days of reperfusion in both animal groups. The staining of tau protein and terminal deoxynucleotidyl transferase-mediated dUTP-biotin in situ nick end labeling (TUNEL) did not show any positive signals in the control brain, but showed positive signals after ischemia with a peak at 24 h and 3 days, respectively. No significant difference was observed in the temporal and spatial patterns of tau and TUNEL stainings between these two groups. These data suggest that GSK3β may have a role in ischemic neuronal cell death, and that the different spatial expression of GSK3β between young and old rat brains may partly explain the vulnerability of older neurons after ischemia. [Neurol Res 2001; 23: 588-592]

Heteropteris aphrodisiaca O. Machado : effects of extract BST 0298 on the oxidative stress of young and old rat brains.

The plant Heteropteris aphrodisiaca O. Machado is widely employed in Brazilian popular medicine as a stimulant, a tonic and a remedy for nervous debility. Several other plant products with similar therapeutic applications may have such effects based on the antioxidant content of polyphenols (gallates, cathecols, etc.) and flavonoids. The aim of this work was to investigate the effects of Heteropteris aphrodisiaca O. Machado extracts on the antioxidant defences and oxidative stress of young and old rat brains. Tests of lipoperoxidation in vitro, comparing H. aphrodisiaca extracts with butylhydroxytoluene (BHT), a classic antioxidant, showed an efficient inhibition of lipoperoxidation (Q(1/2) = 3.3 microg/mL). Chronic treatment of young and old rats with 50 mg plant extract/kg body weight resulted in a significant increase in superoxide dismutase (SOD) activities (40%) in the brain of old rats, but no changes in catalase and glutathione peroxidase (GPX). No significant variations in antioxidant enzyme activities were observed in the brains of young rats. However, significantly lower levels of lipoperoxidation (30%) were detected in the brain of young rats upon plant extract administration, suggesting that H. aphrodisiaca extracts reduced the oxidative stress to brain lipids.

Fibronectin is a binding partner for the myelin-associated glycoprotein (siglec-4a)

The myelin-associated glycoprotein (MAG) mediates cell–cell interactions between myelinating glial cells and neurons. Here we describe the extracellular matrix glycoprotein fibronectin as a binding partner of MAG. It has been identified by affinity precipitation with MAG-Fc from NG108-15 cells and by microsequencing of two peptides derived from a 210-kDa protein band. Western blot analysis showed that fibronectin is also present in MAG binding partners isolated from N 2A (murine neuroblastoma) cells, rat brain and rat spinal cord. Different fibronectin isoforms have been isolated from brains of young and adult rats, indicating that the expression of MAG binding fibronectin changes during development.

The Role of L-Carnitine in the Activities of Membrane-Bound Enzymes in the Brains of Aged Rats

Membrane-bound enzymes play a crucial role in neuronal function. These enzymes are thought to be responsible for maintenance of membrane potential and impulse propagation. An altered membrane potential might be responsible for age-related neuronal changes. We evaluated the effect of L-carnitine (300 mg/kg body weight/day) on the activities of membrane bound enzymes (Na+,K+-ATPase, Ca2+-ATPase, and Mg2+-ATPase) and lipid peroxidation in discrete areas of young and aged rat brains. A progressive increase in lipid peroxidation in all five regions of the brain has been observed. The activities of membrane-bound enzymes were found to be decreased significantly in cortex, hippocampus, and striatum. The results show that there is a negative correlation between lipid peroxidation and activities of membrane-bound enzyme. L-Carnitine lowers the status of lipid peroxidation and increases the activity of membrane-bound enzymes. Our results suggest that L-carnitine has a tendency to inhibit lipid peroxidation and thereby helps the brain to maintain the activities of membranebound enzymes.

Morphology and physiology of neurons in the ventral nucleus of the lateral lemniscus in rat brain slices.

The ventral nucleus of the lateral lemniscus (VNLL) is a prominent neuronal group that lies within the auditory pathway connecting the auditory lower brainstem and midbrain. Previous physiologic studies showed that VNLL neurons respond mainly to contralaterally presented sounds and display various firing patterns. To understand better the role that VNLL neurons play in transmitting and processing of auditory information, we examined the morphology of VNLL neurons and their cellular physiology in young rat brain slices. We made whole-cell patch-clamp recordings and labeled cells intracellularly with neurobiotin to investigate the relation between morphologic neuronal types, intrinsic membrane properties, and postsynaptic responses. VNLL neurons fell into two distinct morphologic groups, i.e., bushy cells and stellate cells, based on their dendritic patterns. Stellate cells were grouped further into stellate I, II, and elongate cells according to soma shape, dendritic branches, and orientation. Bushy cells showed an onset firing pattern and a nonlinear current-voltage relationship. All three subtypes of stellate cells had a linear current-voltage relationship, but exhibited different firing patterns. Stellate I cells showed regular and onset-pause firing patterns, whereas stellate II cells showed adapting and elongate cells showed burst firing patterns. Bushy cells and stellate cells responded to stimulation of the lateral lemniscus with excitatory and/or inhibitory synaptic potentials. These results suggest that the VNLL is a heterogeneous neuronal group and that it contains many channels for processing different kinds of auditory information. Neuronal morphology and intrinsic membrane properties contribute to the behavior of individual neurons.