Number Of Nissl-stained Neurons Research Articles

Aminochrome Induces Neuroinflammation and Dopaminergic Neuronal Loss: A New Preclinical Model to Find Anti-inflammatory and Neuroprotective Drugs for Parkinson's Disease.

Studies have suggested aminochrome as an endogenous neurotoxin responsible for the dopaminergic neuron degeneration in Parkinson's disease (PD). However, neuroinflammation, an important alteration in PD pathogenesis, has been strictly induced in vitro by aminochrome. The aim of this study was to characterize the neuroinflammation induced in vivo by aminochrome. Wistar rats (male, 250-270g) received a unilateral single dose by stereotaxic injection of saline into three sites in the striatum in the negative control group, or 32nmol 6-hydroxydopamine (6-OHDA) in the positive control, or 6nmol aminochrome. After 14 days, histological and molecular analyses were performed. We observed by immunofluorescence that aminochrome, as well as 6-OHDA, induced an increase in the number of Iba-1+ cells and in the number of activated (Iba-1+/ CD68+) microglia. An increase in the number of S100b+ cells and in the GFAP expression were also evidenced in the striatum and the SNpc of animals from aminochrome and positive control group. Dopaminergic neuronal loss was marked by reduction of TH+ cells and confirmed with reduction in the number of Nissl-stained neurons in the SNpc of rats from aminochrome and positive control groups. In addition, we observed by qPCR that aminocrhome induced an increase in the levels of IL-1β, TNF-α, NLRP3, CCL5 and CCR2 mRNA in the SNpc. This work provides the first evidence of microgliosis, astrogliosis and neuroinflammation induced by aminochrome in an in vivo model. Since aminochrome is an endogenous molecule derived from dopamine oxidation present in the targeted neurons in PD, these results reinforce the potential of aminochrome as a useful preclinical model to find anti-inflammatory and neuroprotective drugs for PD. Aminochrome induced dopaminergic neuronal loss, microglial activation, astroglial activation and neuroinflammation marked by an increase in NLRP3, IL1β, TNF-α, CCL2, CCL5 and CCR2.

Chapter 31 - The intermediate nucleus in humans: Cytoarchitecture, chemoarchitecture, and relation to sleep, sex, and Alzheimer disease

The intermediate nucleus of Brockhaus (INH), also known as the interstitial nucleus of the anterior hypothalamus-1 of Allen and Gorski (INAH-1), the sexually dimorphic nucleus of Swaab and colleagues (SDN), and the ventrolateral preoptic nucleus of Saper and colleagues (VLPO), is a cluster of largely galanin-expressing neurons in the lateral preoptic area, at the level of the crossing of the anterior commissure and dorsal to the supraoptic nucleus. The number of Nissl-stained neurons in the INH has been reported to be larger in men than women and to decrease with aging, although these findings have been controversial, in part because of differences in patient populations and methods used to assess the nucleus. However, recent studies have confirmed that the number of galanin-immunoreactive INH neurons is larger in men than women and decreases with age and have reported further loss with Alzheimer disease. The galanin-immunoreactive VLPO neurons have been thought to drive sleep behavior in many species, and their numbers in older humans correlate with the amount of consolidated sleep they experience. Sleep differences between men and women, during aging, and with Alzheimer disease may also depend upon the integrity of this nucleus.

Effects of Tualang honey in modulating nociceptive responses at the spinal cord in offspring of prenatally stressed rats

ObjectiveThis study was done to determine whether Tualang honey could prevent the altered nociceptive behaviour, with its associated changes of oxidative stress markers and morphology of the spinal cord, among the offspring of prenatally stressed rats. MethodsPregnant rats were divided into three groups: control, stress, and stress treated with Tualang honey. The stress and stress treated with Tualang honey groups were subjected to restraint stress from day 11 of pregnancy until delivery. Ten week old male offspring (n = 9 from each group) were given formalin injection and their nociceptive behaviours were recorded. After 2 h, the rats were sacrificed, and their spinal cords were removed to assess oxidative stress activity and morphology. Nociceptive behaviour was analysed using repeated measures analysis of variance (ANOVA), while the levels of oxidative stress parameters and number of Nissl-stained neurons were analysed using a one-way ANOVA. ResultsThis study demonstrated that prenatal stress was associated with increased nociceptive behaviour, changes in the oxidative stress parameters and morphology of the spinal cord of offspring exposed to prenatal stress; administration of Tualang honey reduced the alteration of these parameters. ConclusionThis study provides a preliminary understanding of the beneficial effects of Tualang honey against the changes in oxidative stress and neuronal damage in the spinal cord of the offspring of prenatally stressed rats.

Neuroprotective and Antiapoptotic Potential of Trigonelline in a Striatal 6-Hydroxydopamine Rat Model of Parkinson’s Disease

Considering neuroprotective and antioxidant effects of trigonelline, our study was undertaken to evaluate its protective effect in a 6-hydroxydopamine-induced model of Parkinson’s disease (PD) in rats. Unilateral intrastriatal 6-OHDA-lesioned rats were pretreated with trigonelline at doses of 50 and 100 mg/kg. Significant rotational behavior, a significant reduction in the number of Nissl-stained neurons on the left side of the substantia nigra pars compacta (SNC), increased apoptosis, enhanced levels of malondialdehyde (MDA) and nitrite, and a lower level of glutathione (GSH) were observed in 6-OHDA-lesioned rats. Trigonelline at a dose of 100 mg/kg significantly reduced rotations, prevented reduction of SNC neurons, prevented apoptosis, and restored the MDA level. These results suggest that pre-lesion trigonelline treatment exerts dose-dependent neuroprotective and antiapoptotic effects under conditions of 6-OHDA toxicity and may be, henceforth, advantageous for the management of early PD.

Calcium-binding proteins in focal cortical dysplasia.

SummaryObjectiveAlterations in γ‐aminobutyric acid (GABA)‐ergic cortical neurons have been reported in focal cortical dysplasia (FCD)Ia/IIIa, a malformation of cortical development associated with drug‐resistant epilepsy. We compared numbers of neurons containing calcium‐binding proteins parvalbumin (PV), calbindin (CB), and calretinin (CR) and densities of respective fibers in lateral temporal lobe surgical specimens of 17 patients with FCD with 19 patients who underwent anterior temporal lobe resection due to nonlesional temporal lobe epilepsy (non‐FCD) as well as with 7 postmortem controls.Methods PV‐, CB‐, and CR‐immunoreactive (IR) neurons were quantitatively investigated with use of two‐dimensional cell counting and densitometry (reflecting mainly IR fibers) in cortical layers II, IV, and V.ResultsNumbers of PV‐IR neurons, ratios of PV‐containing to Nissl‐stained neurons (correcting for eventual cell loss), and densities of PV‐IR were higher in layer II of the cortex of FCD compared to non‐FCD patients. Similarly, densities of CB‐IR and CR‐IR were also higher in layers II and V, respectively, of FCD than of non‐FCD patients. Comparison with postmortem controls revealed significant higher cell numbers and fiber labeling for all three calcium‐binding proteins in FCD cortex, whereas numbers of Nissl‐stained neurons did not vary between FCD, non‐FCD, and postmortem controls. In non‐FCD versus postmortem controls, ratios of calcium‐binding protein‐IR cells to Nissl‐stained neurons were unchanged in most instances except for increased CB/Nissl ratios and CB‐IR densities in all cortical layers.SignificanceIncreased numbers of PV neurons and fiber labeling in FCD compared to nondysplastic epileptic temporal neocortex and postmortem controls may be related to cortical malformation, whereas an increased number of CB‐IR neurons and fiber labeling both in FCD and non‐FCD specimens compared with postmortem controls may be associated with ongoing seizure activity. The observed changes may represent increased expression of calcium‐binding proteins and thus compensatory mechanisms for seizures and neuronal loss in drug‐resistant epilepsy.

Carnosine Exerts Neuroprotective Effect Against 6-Hydroxydopamine Toxicity in Hemiparkinsonian Rat

Parkinson's disease (PD) is the second most common disorder of the central nervous system due to the degeneration of mesencephalic dopaminergic neurons. Current treatments for PD have a symptomatic relief strategy with no prevention of disease progression. Due to the neuroprotective and antiapoptotic potential of the natural dipeptide carnosine, this study was conducted to assess its beneficial effect in 6-hydroxydopamine (6-OHDA)-induced model of PD in rat. Unilateral intrastriatal 6-OHDA-lesioned rats received i.p. carnosine at a dose of 250mg/kg twice at an interval of 24h, which started presurgery. Apomorphine caused contralateral rotations, a significant reduction in the number of Nissl-stained neurons on the left side of the substantia nigra, and increased apoptosis was observed with enhanced oxidative stress burden in 6-OHDA-lesioned rats. Carnosine pretreatment significantly reduced rotations, attenuated apoptosis, and restored malondialdehyde and nitrite content and catalase activity with no significant effect on reduced glutathione (GSH). These results indicate that prelesion administration of carnosine could exert neuroprotection against 6-OHDA toxicity, and this may be of benefit in patients with early PD.

Antiepileptogenic effect of curcumin on kainate-induced model of temporal lobe epilepsy

Context: Temporal lobe epilepsy (TLE) is an intractable neurological disorder. Curcumin is the bioactive component of turmeric with anti-epileptic and neuroprotective potential.Objective: The beneficial effect of curcumin on the intrahippocampal kainate-induced model of TLE was investigated.Materials and methods: Rats were divided into sham, curcumin-pretreated sham, kainate and curcumin-pretreated kainate groups. The rat model of TLE was induced by unilateral intrahippocampal injection of 4 μg of kainate. Rats received curcumin p.o. at a dose of 100 mg/kg/d starting 1 week before the surgery. Seizure activity (SE) and oxidative stress-related markers were measured. Furthermore, the Timm index for evaluation of mossy fiber sprouting (MFS) and number of Nissl-stained neurons were quantified.Results: All rats in the kainate group had SE, while 28.5% of rats showed seizures in the curcumin-pretreated kainate group. Malondialdehyde and nitrite and nitrate levels significantly increased in the kainate group (p < 0.01 and p < 0.05, respectively), and curcumin significantly lowered these parameters (p < 0.05). Superoxide dismutase activity significantly decreased in the kainate group (p < 0.05) and curcumin did not improve it. Rats in the kainate group showed a significant reduction of neurons in Cornu Ammonis 1 (CA1) (p < 0.05), CA3 (p < 0.005) and hilar (p < 0.01) regions, and curcumin significantly prevented these changes (p < 0.05–0.005). The Timm index significantly increased in the kainate group (p < 0.005), and curcumin significantly lowered this index (p < 0.01).Discussion and conclusion: Curcumin pretreatment can attenuate seizures, lower some oxidative stress markers, and prevent hippocampal neuronal loss and MFS in the kainate-induced model of TLE.

Neuroprotective actions of the synthetic estrogen 17alpha-ethynylestradiol in the hippocampus.

17alpha-ethynylestradiol (EE2), a major constituent of many oral contraceptives, is similar in structure to 17beta-estradiol, which has neuroprotective properties in several animal models. This study explored the potential neuroprotective actions of EE2 against kainic and quinolinic acid toxicity in the hippocampus of adult ovariectomized Wistar rats. A decrease in the number of Nissl-stained neurons and the induction of vimentin immunoreactivity in astrocytes was observed in the hilus of the dentate gyrus of the hippocampus after the administration of either kainic acid or quinolinic acid. EE2 prevented the neuronal loss and the induction of vimentin immunoreactivity induced by kainic acid at low (1 microg/rat) and high (10-100 microg/rat) doses and exerted a protection against quinolinic acid toxicity at a low dose (1 microg/rat) only. These observations demonstrate that EE2 exerts neuroprotective actions against excitotoxic insults. This finding is relevant for the design of new neuroprotective estrogenic compounds.

Neuroprotective effect of genistein in 6‐hydroxydopamine Hemi‐parkinsonian rat model

A large body of experimental evidence supports a role for oxidative stress as a mediator of nerve cell death in Parkinson's disease (PD). Phytoestrogens such as genistein have been reported to prevent neuronal degeneration caused by increased oxidative burden, therefore, this study examined whether genistein administration at a high dose would attenuate behavioral and structural abnormalities in an experimental model of PD in rat. For this purpose, unilateral intrastriatal 6-hydroxydopamine (6-OHDA, 12.5 microg/5 microL of saline-ascorbate)-lesioned rats were intraperitoneally pretreated with a single and high dose of genistein (10 mg/kg) 1 h before surgery. Apomorphine-induced rotations and the number of Nissl-stained neurons in the substantia nigra pars compacta (SNC) were counted after 2 weeks. Genistein administration could attenuate the rotational behavior in lesioned rats and protect the neurons of SNC against 6-OHDA toxicity. Genistein administration has a protective effect against 6-OHDA toxicity.

Neuroprotective effect of genistein in 6-hydroxydopamine hemi-Parkinsonian rat model

A large body of experimental evidence supports a role for oxidative stress as a mediator of nerve cell death in Parkinson-s disease (PD). Phytoestrogens such as genistein have been reported to prevent neuronal degeneration caused by increased oxidative burden, therefore, this study examined whether genistein administration at a high dose would attenuate behavioral and structural abnormalities in an experimental model of PD in rat. For this purpose, unilateral intrastriatal 6-hydroxydopamine (6-OHDA, 12.5 μg/5 μL of saline-ascorbate)- lesioned rats were intraperitoneally pretreated with a single and high dose of genistein (10 mg/kg) 1 h before surgery. Apomorphine-induced rotations and the number of Nissl-stained neurons in the substantia nigra pars compacta (SNC) were counted after 2 weeks. Genistein administration could attenuate the rotational behavior in lesioned rats and protect the neurons of SNC against 6-OHDA toxicity. Genistein administration has a protective effect against 6-OHDA toxicity.

Expression of neuronal nitric oxide synthase in the hippocampal formation in affective disorders

Hippocampal output is increased in affective disorders and is mediated by increased glutamatergic input via N-methyl-D-aspartate (NMDA) receptor and moderated by antidepressant treatment. Activation of NMDA receptors by glutamate evokes the release of nitric oxide (NO) by the activation of neuronal nitric oxide synthase (nNOS). The human hippocampus contains a high density of NMDA receptors and nNOS-expressing neurons suggesting the existence of an NMDA-NO transduction pathway which can be involved in the pathogenesis of affective disorders. We tested the hypothesis that nNOS expression is increased in the human hippocampus from affectively ill patients. Immunocytochemistry was used to demonstrate nNOS-expressing neurons in sections obtained from the Stanley Consortium postmortem brain collection from patients with major depression (MD, N = 15), bipolar disorder (BD, N = 15), and schizophrenia (N = 15) and from controls (N = 15). nNOS-immunoreactive (nNOS-IR) and Nissl-stained neurons were counted in entorhinal cortex, hippocampal CA1, CA2, CA3, and CA4 subfields, and subiculum. The numbers of Nissl-stained neurons were very similar in different diagnostic groups and correlated significantly with the number of nNOS-IR neurons. Both the MD and the BD groups had greater number of nNOS-IR neurons/400 microm(2) in CA1 (mean +/- SEM: MD = 9.2 +/- 0.6 and BD = 8.4 +/- 0.6) and subiculum (BD = 6.7 +/- 0.4) when compared to control group (6.6 +/- 0.5) and this was significantly more marked in samples from the right hemisphere. These changes were specific to affective disorders since no changes were seen in the schizophrenic group (6.7 +/- 0.8). The results support the current view of the NMDA-NO pathway as a target for the pathophysiology of affective disorders and antidepressant drug development.

Neuroprotective effects of soy phytoestrogens in the rat brain

Soy extracts are widely used as an alternative to hormone replacement therapy for the treatment of menopausal symptoms. Soy phytoestrogens, such as genistein, may act on the nervous system, affecting mood, cognitive function and behavior. In addition, several studies suggest that soy phytoestrogens are neuroprotective. The hypothesis of the present study was that soy extracts may exert neuroprotection and that this effect is mediated by phytoestrogens such as genistein. To test this hypothesis we assessed whether an acute administration of soy extract or genistein in vivo affects hippocampal neuronal loss induced by the systemic administration of kainic acid to adult Wistar female rats. One week after ovariectomy, animals received one intraperitoneal injection of soy extract (0.2, 1, 2 or 20 mg/kg), one injection of genistein (0.1, 1 or 10 mg/kg) or one injection of vehicle. Thirty minutes later, all animals received one intraperitoneal injection of kainic acid (7 mg/kg) or vehicle. One week after the injections, all animals were fixed by perfusion and the number of Nissl-stained neurons in the hilus of the dentate gyrus was estimated by the optical disector method. Administration of soy extract, even at high doses, did not induce neuronal loss and did not increase neuronal degeneration after kainic acid injury. On the contrary, soy extract at doses ranging from 1 to 20 mg/kg prevented neuronal loss induced by kainic acid. Genistein showed neuroprotective effects only at high dose (10 mg/kg), suggesting that other components in the soy extract are involved in the neuroprotective effect.

Neuroprotection by the steroids pregnenolone and dehydroepiandrosterone is mediated by the enzyme aromatase.

Pregnenolone and dehydroepiandrosterone (DHEA) are sex hormone precursors and neuroprotective steroids. Effects of pregnenolone and DHEA may be in part mediated by their conversion to testosterone and by the consecutive conversion of testosterone to estradiol by the enzyme aromatase. This enzyme is induced in reactive astrocytes after different forms of neurodegenerative lesions and the resultant local production of estradiol in the brain has been shown to be neuroprotective. The participation of aromatase in the neuroprotective effect of pregnenolone and DHEA has been assessed in this study. The protective effect of different doses (12.5, 25, 50, and 100 mg/kg) of pregnenolone or DHEA, against systemic kainic acid (7 mg/kg b.w.), was assessed on hippocampal hilar neurons in gonadectomized Wistar male rats. To determine whether the neuroprotective effect of pregnenolone and DHEA was dependent on their conversion to estradiol, the aromatase inhibitor fadrozole (4.16 mg/ml) was administered using subcutaneous osmotic minipumps. The number of Nissl-stained neurons in the hilus of the dentate gyrus of the hippocampal formation was estimated by the optical disector method. The administration of kainic acid resulted in a significant decrease in the number of hilar neurons compared to rats injected with vehicles. Pregnenolone and DHEA showed a dose-dependent protective effect of hilar neurons against kainic acid. The administration of the aromatase inhibitor fadrozole blocked the neuroprotective effect of pregnenolone and DHEA. These findings suggest that estradiol formation by aromatase mediates neuroprotective effects of pregnenolone and DHEA against excitotoxic-induced neuronal death in the hippocampus.