Biomedical subjects

Dean E Dluzen

Publications and source records attributed to Dean E Dluzen.

At least 19 recordsLinked to original sources

PubMed2006

Gender differences in Parkinson's disease.

OBJECTIVE: To investigate gender differences in basic disease characteristics, motor deterioration and nigrostriatal degeneration in Parkinson's disease (PD). METHODS: We studied 253 consecutive PD patients who were not receiving levodopa or dopamine agonists (disease duration < or = 10 years). We investigated the influence of gender and oestrogen status on: (1) age at onset, (2) presenting symptom, (3) severity and progression of motor symptoms (Unified Parkinson's Disease Rating Scale III (UPDRS-III) scores) and (4) amount and progression of nigrostriatal degeneration ([123I]FP-CIT single photon emission computed tomography measurements). RESULTS: Age at onset was 2.1 years later in women (53.4 years) than in men (51.3 years). In women, age at onset correlated positively with parity, age at menopause and fertile life span. Women more often presented with tremor (67%) than men (48%). Overall, patients presenting with tremor had a 3.6 year higher age at onset and a 38% slower UPDRS-III deterioration. Mean UPDRS-III scores at disease onset were equal for both genders, as was the rate of deterioration. Women had a 16% higher striatal [123I]FP-CIT binding than men at symptom onset and throughout the course of PD. CONCLUSIONS: Our results suggest that, in women, the development of symptomatic PD may be delayed by higher physiological striatal dopamine levels, possibly due to the activity of oestrogens. This could explain the epidemiological observations of a lower incidence and higher age at onset in women. Women also presented more often with tremor which, in turn, is associated with milder motor deterioration and striatal degeneration. Taken together, these findings suggest a more benign phenotype in women with PD.

Adult↗

PubMed2006

Effects of estrogen and related agents upon methamphetamine-induced neurotoxicity within an impaired nigrostriatal dopaminergic system of ovariectomized mice.

Estrogen increases methamphetamine (MA)-induced neurotoxicity within the impaired nigrostriatal dopaminergic (NSDA) system of ovariectomized female mice, as defined by enhanced striatal dopamine (DA) depletion. In this study we compared the effects of a lower dose of estradiol benzoate (EB, 1 microg) with related agents--tamoxifen (TMX, 12.5 microg), testosterone (5 microg) and dehydroepiandrosterone (DHEA, 3 mg) in this paradigm. In experiment 1, ovariectomized mice received an initial treatment with MA. At 1 week after MA, mice were treated with EB, TMX, testosterone, DHEA or oil vehicle and 24 h later a second MA treatment. Striatal DA and 3,4-dihydroxyphenylacetic acid (DOPAC) concentrations in the MA-treated groups were decreased compared to the non-MA-treated control. Neither EB nor any of the other agents tested showed enhanced neurodegenerative or neuroprotective effects against a second MA invasion. To verify that estrogen was capable of showing a neuroprotective effect under a condition of two administrations of MA, in experiment 2, EB was administered either once or twice prior to each of the two MA treatments. EB treatment prior to the first MA invasion or first and second MA protected the NSDA system against DA and DOPAC depletion. These results imply that a lower dose of EB, TMX, testosterone and DHEA cannot exert neurodegenerative or neuroprotective effects in the impaired NSDA model. However, EB administered prior to the introduction of neurotoxicity can protect the NSDA system. This study may provide an understanding of the variations in results on the effects of estrogen upon the NSDA neurodegenerative disorder, Parkinson's disease.

3,4-Dihydroxyphenylacetic Acid↗

PubMed2006

Sex differences in methamphetamine-evoked striatal dopamine of mice are reversed by nomifensine.

Male mice show more severe striatal dopamine depletions to the psychostimulant, methamphetamine (MA). To gain some understanding for this sex difference, we examined MA-evoked dopamine (DA) responses from superfused striatal tissue fragments of male and female mice under conditions of a dopamine transporter which was either unaltered (Experiment 1) or inhibited, with use of the drug, nomifensine (Experiment 2). In Experiment 1, MA-evoked DA was significantly greater in male versus female mice. In Experiment 2, diminished, albeit statistically significant, DA responses to MA infusion in the presence of nomifensine were obtained from striatal tissue of female, but not male, mice. In Experiment 3, potassium-evoked DA responses and sex differences were abolished in the presence of nomifensine. These data demonstrate a clear sex difference in DA responses to MA. Interestingly, under conditions where dopamine transporter function is inhibited, MA retains its ability to evoke DA. However, this capacity was only observed within striatal tissue fragments of female mice and not under conditions of potassium-evoked DA. These results indicate an additional component for the bases of sex differences in nigrostriatal dopaminergic function in health and in disease. In particular, the present findings have important implications in suggesting an alternative, non-traditional, mechanism for MA effects and indicate that such a function is limited to females.

Animals↗

PubMed2006

Differential protective properties of estradiol and tamoxifen against methamphetamine-induced nigrostriatal dopaminergic toxicity in mice.

Mechanisms implicated in protective potential of estrogens are poorly understood. Tamoxifen, a selective estrogen receptor modulator (SERM), presents a neuroprotective effect against methamphetamine (MA)- and methoxy-phenyltetrahydropyridine (MPTP)-induced toxicity when used alone but abolishes estrogen's positive effects when combined with this hormone. In order to understand tamoxifen's protective properties, the present study compared it to estradiol on several markers of dopaminergic neurons to achieve a relatively comprehensive comparison between these two agents. Estradiol benzoate (E) or tamoxifen were used at different concentrations (E: 1, 10 or 40 microg; tamoxifen: 12.5, 125 or 500 microg) 24 h prior to a MA injection in ovariectomized CD-1 mice. The effects of the lesion and treatments were studied on striatal dopamine (DA) concentrations, dopamine and monoamine vesicular transporters (DAT and VMAT2), and preproenkephalin (PPE) mRNA levels. Both treatments, at all concentrations, prevented the MA-induced decrease of striatal DA concentrations and VMAT2 binding. Only E was able to prevent loss of DAT binding in the lateral striatum and to attenuate the MA-induced increase in striatal PPE mRNA levels (at 1 or 40 microg). Therefore, in this paradigm, E and tamoxifen differentially modulated MA-induced neuronal damages. While both treatments prevented the DA decrease, E protected more efficiently other dopaminergic parameters suggesting that overall E is more effective than tamoxifen as a neuroprotectant of the nigrostriatal dopaminergic system.

Animals↗

PubMed2006

Sex differences in methamphetamine-evoked striatal dopamine output are abolished following gonadectomy: comparisons with potassium-evoked output and responses in prepubertal mice.

Sex differences are reported for methamphetamine (MA)-induced neurotoxicity of the nigrostriatal dopaminergic system. In an attempt to understand some of the bases for these differences, we investigated MA-evoked dopamine (DA) responses from superfused striatal tissue fragments of intact and male and female CD-1 mice. These responses were compared with that of gonadectomized mice, potassium-evoked DA responses in intact mice and responses in prepubertal mice. In experiment 1, DA responses were tested using infusion of MA at doses of 1, 10, 100 and 1,000 microM. In intact mice, mean peak MA-evoked DA responses were consistently increased and significantly greater in male vs. female mice at the 1,000 microM dose. No such significant differences were observed between gonadectomized male vs. female mice (experiment 2). In contrast to MA, potassium-stimulated DA responses were increased in intact female mice, with statistically significant differences at doses of 30 and 60 mM (experiment 3). No statistically significant differences between intact prepubertal male and female mice were obtained in response to a 1,000 microM dose of MA (experiment 4) or to a 60 mM dose of potassium (experiment 5). These results indicate that intact male mice show greater sensitivity to MA-evoked DA output. This sex difference is abolished following gonadectomy, is not observed with potassium, nor is it present in prepubertal mice. The increased sensitivity to MA shown by intact males may be related to the greater degree of striatal dopaminergic neurotoxicity observed in male mice in response to this psychostimulant and appears to be attributable to differences in gonadal steroid hormones between male and female mice.

Animals↗

PubMed2006

Estrogen prevents neuroprotection by caffeine in the mouse 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine model of Parkinson's disease.

Epidemiological studies have strongly linked caffeine consumption with a reduced risk of developing Parkinson's disease (PD) in men. Interestingly, in women, this inverse association is present only in those who have not taken postmenopausal estrogens, suggesting an interaction between the influences of estrogen and caffeine use on the risk of PD. To explore a possible biological basis for this interaction, we systematically investigated how the neuroprotective effect of caffeine is influenced by gender, ovariectomy (OVX), and then exogenous estrogen in the mouse 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) model of PD. (1) Caffeine treatment produced a dose-dependent attenuation of MPTP-induced striatal dopamine loss in both young and retired breeder (RB) male, but not female, mice. (2) In female mice (both young and RB), caffeine was less potent or altogether ineffective as a neuroprotectant after sham surgery compared to OVX or after OVX plus estrogen replacement compared to OVX plus placebo treatment. (3) Estrogen treatment also prevented the protection of caffeine against dopamine loss in young male mice. (4) Consistent with the putative protective effect of estrogen, female and OVX plus estrogen mice were relatively resistant to MPTP toxicity compared to male and OVX plus placebo mice, respectively. (5) There was no overall difference in brain levels of caffeine and its metabolites between OVX plus placebo and OVX plus estrogen mice. Together, these results suggest that estrogen can occlude and thereby prevent the neuroprotective effect of caffeine in a model of PD neurodegeneration, supporting a biological basis for the interaction between estrogen and caffeine in modifying the risk of PD.

3,4-Dihydroxyphenylacetic Acid↗

PubMed2006

Effect of estrogen upon methamphetamine-induced neurotoxicity within the impaired nigrostriatal dopaminergic system.

In the present study, we investigated whether estrogen remains effective as a neuroprotectant within an impaired nigrostriatal dopaminergic (NSDA) system of gonadectomized female and male mice. In Experiment 1, mice were treated with four different regimens of methamphetamine (MA) to establish a protocol for an impaired NSDA system to be used in subsequent experiments. Based upon the results of Experiment 1, in Experiment 2 gonadectomized female mice received a treatment with either control (saline), low- or high-dose of MA to produce an initial NSDA impairment. At one week post-MA, mice received either estradiol benzoate (10 microg) or vehicle followed 24 h later with low-MA or saline. Estrogen altered the toxic effects of the second invasion of MA as indicated by a significant decrease in striatal dopamine (DA) and 3,4-dihydroxyphenylacetic acid (DOPAC) concentrations. In addition, DA and DOPAC depletion was greater in high- vs. low-dose MA. In gonadectomized male mice (Experiment 3), striatal DA and DOPAC concentrations showed greater decreases following high-, vs. low-doses of MA; however, estrogen did not alter these responses. These results demonstrate that the capacity for estrogen to protect or worsen MA-induced neurotoxicity of dopaminergic neurons is limited to female mice and depends on the condition of the NSDA system.

3,4-Dihydroxyphenylacetic Acid↗

PubMed2006

Testosterone modulation of striatal dopamine output in orchidectomized mice.

Three experiments are presented in which dopamine (DA) responses from superfused striatal tissue of orchidectomized (ORCH) mice treated or not with testosterone (T) are compared. In experiment 1, potassium-stimulated DA output was significantly greater in ORCH vs. ORCH+T mice. This profile was reversed when reserpine was infused in experiment 2, with DA output being significantly greater in ORCH+T vs. ORCH mice. In experiment 3, the amount of DA recovered following infusion of DA indicated no statistically significant differences in DA recoveries between ORCH and ORCH+T mice as tested in this paradigm. The findings that both potassium- and reserpine-induced DA responses are altered significantly by T suggests that one potential site of T action might involve the storage/uptake of DA within the vesicles of these neurons. Such results have important implications with regard to understanding the sex differences that are present in nigrostriatal dopaminergic function within health and diseased states.

Adrenergic Uptake Inhibitors↗

PubMed2006

Rotenone produces opposite effects upon mouse striatal dopamine function as a result of environmental temperature.

Rotenone is a commonly used pesticide that can function as an environmental neurotoxin. Rotenone is a known mitochondrial complex I inhibitor which can lead to oxidative stress and results in dopaminergic cell death. Another environmental factor known to exacerbate oxidative stress and result in striatal dopaminergic cell death is elevated environmental temperature. In this study we evaluated the effects of a single injection of various doses of rotenone (0.65, 1.3 and 2.6 mg/kg) on striatal dopamine (DA) and 3,4-dihydroxyphenylacetic acid (DOPAC) concentrations in CD-1 mice and compared this with a single injection of two doses of methamphetamine (MA - 10 or 20 mg/kg), a known striatal DA depleting agent, as administered to mice maintained at 21 degrees C (Experiment 1). These results were then compared to striatal DA and DOPAC concentrations of mice treated with rotenone (1.3 or 2.6 mg/kg) or MA (10 or 20 mg/kg) administered to mice maintained at 28 degrees C (Experiment 2). A single injection of rotenone to mice maintained at 21 degrees C resulted in a significant increase in DA and decrease in DOPAC concentrations for all doses tested compared to controls, whereas a single injection of MA at the same temperature resulted in a significant decrease in DA and no change in DOPAC concentrations. At a temperature of 28 degrees C, a single injection of rotenone resulted in a significant decrease in both DA and DOPAC concentrations similar to that seen with the MA-treated mice. Collectively, these results indicate that rotenone interacts with environmental temperature to produce opposite effects upon striatal DA concentrations -- significantly increasing striatal DA when administered at 21 degrees C and significantly decreasing striatal DA when administered at 28 degrees C, while producing similar decreases in striatal DOPAC under both temperatures.

3,4-Dihydroxyphenylacetic Acid↗

PubMed2006

Estrogen, testosterone, and methamphetamine toxicity.

The gonadal steroid hormone, estrogen, can diminish the degree of striatal dopamine depletion resulting from methamphetamine. In this article, we describe the conditions of this estrogen neuroprotection as well as the potential for estrogen and testosterone to enhance methamphetamine-induced neurodegeneration of the nigrostriatal dopaminergic system. When administered prior to a neurotoxic regimen of methamphetamine, estrogen significantly decreases the amount of striatal dopamine depletion in intact or gonadectomized female, but not male, mice. This capacity for estrogen to function as a neuroprotectant can occur quite rapidly, at 30 min prior to methamphetamine administration, and with relatively low doses of estrogen (1 microg estradiol benzoate). Estrogen remains an effective neuroprotectant in neonatally gonadectomized female mice treated with testosterone, but not in female mice that were gonadectomized prior to puberty. Nor does estrogen demonstrate any beneficial effects when administered after methamphetamine. Recent data have indicated some conditions where gonadal steroids can increase the extent of striatal neurodegeneration in response to methamphetamine. Specifically, when some existing perturbation is present in the nigrostriatal dopaminergic system, treatment with estrogen enhances the extent of striatal dopamine depletion to methamphetamine. Similarly, increased striatal dopamine depletion to methamphetamine is observed in gonadectomized male mice treated with testosterone.

Animals↗

PubMed2005

Dopamine transporter function differences between male and female CD-1 mice.

It has been reported that male mice are more susceptible to the neurotoxic effects of methamphetamine (MA) upon the nigrostriatal dopaminergic (NSDA) system. Since MA utilizes the dopamine transporter (DAT) to exert its effects, in the present study, we tested for differences in the dynamics of DAT function between male and female mice as an approach to understand some of the bases for this sex difference in MA-induced NSDA neurotoxicity. To accomplish this goal, in Experiment 1, the amount of dopamine (DA) obtained following DA infusion into the superfused striatal tissue fragments of male and female mice was measured while in Experiment 2 responses to the DA uptake blocker, nomifensine (NMF), were assessed in these preparations. The differences obtained to these treatments demonstrate that marked differences in DA transporter activity exist between male and female mice. When combining the DA and DOPAC measures from these two experiments, the data suggest that the female mice show a more active and efficient recovery and vesicular packaging of extracellular DA. These findings have important implications for sex differences in NSDA functions and responses to neurotoxins which enter the neurons via the DAT.

3,4-Dihydroxyphenylacetic Acid↗

PubMed2005

Gender differences in modulatory effects of tamoxifen upon the nigrostriatal dopaminergic system.

It has been demonstrated that the gonadal steroid hormone estrogen can exert neuroprotective effects upon the nigrostriatal dopaminergic (NSDA) system against methamphetamine (MA)-induced neurotoxicity in female, but not male, mice. In contrast, the anti-estrogen, tamoxifen (TMX) can function as a NSDA neuroprotectant within both female and male mice. In an attempt to understand these effects of TMX, the effects of this anti-estrogen upon both behavioral and neurochemical indices of NSDA function were examined within female and male mice following treatment with MA. In general, TMX exerted markedly different (bi-directional) effects upon NSDA function between female and male mice. Notably, treatment with TMX resulted in a relative decrease in striatal dopamine (DA) and 3,4-dihydroxyphenylacetic acid (DOPAC) concentrations within male mice and a relative increase in female mice when treated with MA to produce a significant gender difference. Similar effects were obtained for locomotor behaviors related with NSDA function. That is, TMX produced increases in horizontal activity, number of movements and total distance traveled within MA-treated female mice resulting in statistically significant gender differences for the two former parameters. For non-locomotor behaviors, like time occupying the center and margin of the cage, TMX-treated male mice showed statistically significant increases and decreases compared within TMX-treated female mice, respectively. These results show that in contrast to the similar neuroprotective effects of TMX upon MA-induced NSDA neurotoxicity, a number of other NSDA indices induced by MA show markedly different response profiles between TMX-treated female and male mice.

Animals↗

PubMed2005

Unconventional effects of estrogen uncovered.

The nigrostriatal dopamine system shows marked gender differences that, in many cases, can be attributable to estrogen. However, the virtual absence of conventional estrogen receptors within the nigrostriatal dopamine system has made it difficult to understand how estrogen can function within this system. Recent findings have helped to uncover how estrogen can affect a discrete function of striatal dopamine-containing neurons--transporter activity--in a manner similar to that achieved through alterations in dopamine D(2) receptors and their associated G protein. These findings suggest that the effects of estrogen on dopamine transporter function could result from a signal transduction interaction involving D(2) receptor-G protein coupling.

Animals↗

PubMed2005

Estrogen, testosterone, and gender differences.

The purpose of this report is to gain some current perspective on the definition, bases, and trends for research associated with gender differences. To accomplish this goal an analysis on the number of citations from a 1994-2004 Medline search with the terms estrogen, testosterone, gender differences, sex differences as well as the combinations of these terms was performed. Other combinations of terms included separate searches of estrogen, testosterone, and their combination within males or females, and an analysis of gender and sex differences with the terms human and animal. The salient results from this survey include: (1) An overall greater ratio of estrogen:testosterone citations when these terms were searched alone or in combination with gender differences; (2) an overall greater ratio of testosterone:estrogen citations when these terms were combined with sex differences or conducted separately within males or females, although this trend was shifting toward decreased testosterone and increased estrogen citation numbers toward the latter years of the survey; (3) a trend for increasing numbers of estrogen and gender differences citations over the period of the survey; (4) a clear indication for the term gender differences to be associated with the search term human; and (5) a very small number of citations when the terms estrogen and testosterone were combined. Interpretations and implications of these results are discussed.

Estrogens↗

PubMed2004

Tamoxifen increases methamphetamine-evoked dopamine output from superfused striatal tissue fragments of male mice.

The antiestrogen, tamoxifen (TMX), has been shown to function as a neuroprotectant against the nigrostriatal dopaminergic (NSDA) neurotoxin, methamphetamine (MA), within male mice. In the present report, we examined the effects of a combined infusion of TMX and MA within superfused striatal tissue fragments of male mice as an approach to understand some of the bases for TMX to function as a NSDA neuroprotectant within male mice. In Experiment 1, a coinfusion of TMX at 1, 10, or 100 pg/ml were all equally effective in increasing MA-evoked dopamine (DA) output as compared with a 0 pg/ml (control) dose. In Experiment 2, we tested whether this effect of TMX was specific for MA-evoked DA output by coinfusing TMX with a depolarizing concentration of potassium chloride (K+ -30 mM). No statistically significant differences were obtained between superfusions of striatal tissue fragments stimulated with K+ in the presence or absence of TMX (100 pg/ml). In Experiment 3, we assessed whether these effects of TMX may be exerted upon the dopamine transporter (DAT) by coinfusing DA (1 microM) in the presence or absence of TMX (100 pg/ml). No differences in DA recovery rates were obtained between superfusions performed in the presence or absence of TMX. Taken together, these results show that the striatum of male mice is very sensitive to the modulatory effects of TMX upon MA-evoked DA output. These effects of TMX appear to be relatively specific for MA-evoked DA output, as K+ -stimulated DA was not altered by TMX, and do not appear to exert these effects by altering dopamine transporter function.

Animals↗

PubMed2004

Dose-response effects of estrogen and tamoxifen upon methamphetamine-induced behavioral responses and neurotoxicity of the nigrostriatal dopaminergic system in female mice.

In the present experiment we evaluated the dose-response effects of estrogen (estradiol benzoate; EB) and tamoxifen (TMX) in modulating the acute behavioral and chronic effects of methamphetamine (MA) upon the nigrostriatal dopaminergic (NSDA) system in ovariectomized (OVX) mice. EB over a range of doses from 1-40 microg resulted in a neuroprotective effect upon the NSDA system as defined by both a preservation of striatal dopamine (DA) concentrations and a decrease in DOPAC/DA ratios. Interestingly, the neuroprotective effect of the 1-microg EB dose occurred in the absence of any statistically significant effect upon the bioassay parameter of uterine weight. With the exception of an increase in stereotypy time as a response to the 40-microg dose, EB at any of the doses tested failed to alter any acute behavioral responses evoked by MA. In response to TMX, a statistically significant NSDA neuroprotectant response was obtained for DOPAC/DA ratios, but not DA concentrations, to doses ranging from 12.5 to 500 microg. No statistically significant effects upon uterine weights were obtained for any of the doses of TMX tested. Behaviorally, TMX at 500 microg had the effect of increasing the amount of time spent in the center of the cage. Taken together these results demonstrate: (1) EB and TMX at relatively low doses can exert a neuroprotective effect against MA; (2) these neuroprotective effects of EB and TMX can occur in the absence of an effect upon the bioassay parameter--uterine weights; (3) the parameter of DOPAC/DA ratio may indicate a more sensitive index of NSDA neuroprotection, and (4) modulatory effects of EB and TMX upon acute behavioral responses of the NSDA system to MA can be distinguished from their neuroprotective actions.

3,4-Dihydroxyphenylacetic Acid↗

PubMed2004

Dopamine transporter as a marker of neuroprotection in methamphetamine-lesioned mice treated acutely with estradiol.

Our laboratories have shown the positive effect of estradiol on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine- and methamphetamine (MA)-induced striatal dopamine (DA) depletion. Most studies on E neuroprotection use chronic administration of the steroid to evaluate its beneficial effect. In the present report, we investigated the neuroprotective potential of 17 beta-estradiol-3-benzoate (E) under acute conditions when administered 24, 12 or 0.5 h before MA. The effects of E on striatal DA and dihydroxyphenylacetic acid (DOPAC) contents, and DA transporter (DAT) protein and mRNA were measured using high-performance liquid chromatography, autoradiography and in situ hybridization, respectively. We observed neuroprotection with an acute dose of E, and also that protection presents a different time course for each dopaminergic marker. DAT mRNA responded more quickly to E than its protein (at 0.5 h vs. 24 h). Also, E treatment 12 h prior to MA resulted in 'normal' (equal to control) DA content, while DAT protein was still decreased as compared to control values. These different responses for each marker may represent different mechanisms of action of E (genomic versus nongenomic). Since most experimental studies use DA content as the sole indicator of nigrostriatal toxicity and examine a single time point following chronic E administration, the present results demonstrate the importance of evaluating differences in temporally dependent responses of DA, DAT protein and mRNA, to achieve a more comprehensive indication of the nigrostriatal state and the means by which E can function as a neuroprotectant in this system.

3,4-Dihydroxyphenylacetic Acid↗

PubMed2004

The effect of gender and the neurotrophin, BDNF, upon methamphetamine-induced neurotoxicity of the nigrostriatal dopaminergic system in mice.

The interactive effects between gender and a selective alteration in the neurotrophin, brain-derived neurotrophic factor (BDNF) upon methamphetamine (MA)-induced neurotoxicity of the nigrostriatal dopaminergic (NSDA) system were assessed. MA treatment produced a greater degree of NSDA neurotoxicity (indicated by greater reductions in corpus striatal dopamine levels) in wild type control BDNF male versus female mice. This sex difference was unaltered in heterozygous mutant BDNF (BDNF +/-) mice and in mice which overexpress BDNF (DBH:BDNF +). Both BDNF mutant conditions resulted in preservation of corpus striatal dopamine levels following MA treatment as compared with their respective MA-treated wild type controls. The relative amount of this preservation was greater in male BDNF mutants, with values being significantly greater than females in the BDNF +/- condition. These results suggest that alterations in BDNF do not alter basic gender differences in MA-induced NSDA neurotoxicity, but may produce a neuroprotection against MA which is relatively greater in males.

Animals↗