High egg retention in Chinook Salmon Oncorhynchus tshawytscha carcasses sampled downstream of a migratory barrier.

Barriers in rivers have the potential to severely decrease functional connectivity between habitats. Failure to pass barriers and reach natal spawning habitat may compromise individual reproductive success, particularly for semelparous, philopatric species that rely on free-flowing rivers to reach natal habitat during their once-in-a-lifetime spawning migrations. To investigate the consequences of in-river barriers on fish spawning success, we quantified egg retention and spawning effort (caudal fin wear) in female Chinook Salmon Oncorhynchus tshawytscha carcasses collected downstream of the Whitehorse Hydro Plant on the upper Yukon River and at a nearby free-flowing tributary (Teslin River) from 2018 to 2020 (~2900 km migrations). Previous studies have demonstrated that a large proportion of fish attempting to reach spawning locations upstream of the hydro plant fail to pass the associated fishway. We estimated nearly all female salmon failing to pass the hydro plant attempted spawning in non-natal habitat downstream, but that these females retained ~34% of their total fecundity compared to ~6% in females from the free-flowing river. Females downstream of the hydro plant also had lower wear on their caudal fin, a characteristic that was correlated with increased egg deposition. Egg retention did not vary across years with different run sizes, and we propose that egg retention downstream of the hydro plant was not driven by density-dependent mechanisms. Findings from this work indicate that female Chinook Salmon can still deposit eggs following failed fish passage and failure to reach natal spawning sites, though egg retention rates are considerably higher and uncertainties remain about reproductive success. We encourage researchers to incorporate carcass surveys into fish passage evaluations for semelparous species to fully account for consequences of failed passage.

Telemetry-Determined Habitat Use Informs Multi-Species Habitat Management in an Urban Harbour.

Widespread human development has led to impairment of freshwater coastal wetlands and embayments, which provide critical and unique habitat for many freshwater fish species. This is particularly evident in the Laurentian Great Lakes, where such habitats have been severely altered over the last century as a result of industrial activities, urbanization, dredging and infilling. In Toronto Harbour, extensive restoration efforts have been directed towards improving the amount and quality of aquatic habitat, especially for fishes. To evaluate the effectiveness of this restoration work, use of the restored area by both target species and the fish community as a whole must be assessed. Individuals from four species (Common Carp, Largemouth Bass, Northern Pike and Yellow Perch) were tagged and tracked continuously for 1 year using an acoustic telemetry array in Toronto Harbour area of Lake Ontario. Daily site fidelity was estimated using a mixed-effects logistic regression model. Daily site fidelity was influenced by habitat restoration and its interactions with species and body size, as well as season and its interactions with species and body size. Daily site fidelity was higher in restored sites compared to non-restored sites for Yellow Perch and Northern Pike, but lower for Largemouth Bass and Common Carp. For all species, daily site fidelity estimates were highest during the summer and lowest during autumn. The approach used here has merit for evaluating restoration success and informing future habitat management activities. Creating diverse habitats that serve multiple functions and species are more desirable than single-function-oriented or single-species-oriented designs.

Targeted spectroscopy in the eye fundus.

Significance: The assessment of biomarkers in the eye is rapidly gaining traction for the screening, diagnosis, and monitoring of ocular and neurological diseases. Targeted ocular spectroscopy is a technology that enables concurrent imaging of the eye fundus and analysis of high-quality spectra from a targeted region within the imaged area. This provides structural, compositional, and functional information of specific regions of the eye fundus from a non-invasive approach to ocular biomarker detection. Aim: The aim of our study was to demonstrate the multimodal functionality and validation of targeted ocular spectroscopy. This was done in vitro, using a reference target and a model eye, and in vivo. Approach: Images and spectra from different regions of a reference target and a model eye were acquired and analyzed to validate the system. Targeted ocular fluorescence spectroscopy was also demonstrated with the same model. Subsequently, in vivo imaging and diffuse reflectance spectra were acquired to assess blood oxygen saturation in the optic nerve head and the parafovea of healthy subjects. Results: Tests conducted with the reference target showed accurate spectral analysis within specific areas of the imaging space. In the model eye, distinct spectral signatures were observed for the optic disc, blood vessels, the retina, and the macula, consistent with the variations in tissue composition and functions between these regions. An ocular oximetry algorithm was applied to in vivo spectra from the optic nerve head and parafovea of healthy patients, showing significant differences in blood oxygen saturation. Finally, targeted fluorescence spectral analysis was performed in vitro. Conclusions: Diffuse reflectance and fluorescence spectroscopy in specific regions of the eye fundus open the door to a whole new range of monitoring and diagnostic capabilities, from assessment of oxygenation in glaucoma and diabetic retinopathy to photo-oxidation and photodegradation in age-related macular degeneration.

Monte-Carlo simulation and tissue-phantom model for validation of ocular oximetry.

Ocular oximetry, in which blood oxygen saturation is evaluated in retinal tissues, is a promising technique for the prevention, diagnosis and management of many diseases and conditions. However, the development of new tools for evaluating oxygen saturation in the eye fundus has often been limited by the lack of reference tools or techniques for such measurements. In this study, we describe a two-step validation method. The impact of scattering, blood volume fraction and lens yellowing on the oximetry model is investigated using a tissue phantom, while a Monte Carlo model of the light propagation in the eye fundus is used to study the effect of the fundus layered-structure. With this method, we were able to assess the performance of an ocular oximetry technique in the presence of confounding factors and to quantify the impact of the choroidal circulation on the accuracy of the measurements. The presented strategy will be useful to anyone involved in studies based on the eye fundus diffuse reflectance.

Specific role of dopamine D1 receptors in spinal network activation and rhythmic movement induction in vertebrates.

Dopamine (DA) is well-recognized for its determinant role in the modulation of various brain functions. DA was also found in in vitro isolated invertebrate preparations to activate per se the central pattern generator for locomotion. However, it is less clear whether such a role as an activator of central neural circuitries exists in vertebrate species. Here, we studied in vivo the effects induced by selective DA receptor agonists and antagonists on hindlimb movement generation in mice completely spinal cord-transected (Tx) at the low-thoracic level (Th9/10). Administration of D1/D5 receptor agonists (0.5-2.5 mg kg(-1), i.p.) was found to acutely elicit rhythmic locomotor-like movements (LMs) and non-locomotor movements (NLMs) in untrained and non-sensory stimulated animals. Comparable effects were found in mice lacking the D5 receptor (D5KO) whereas D1/D5 receptor antagonist-pretreated animals (wild-type or D5KO) failed to display D1/D5 agonist-induced LMs. In contrast, administration of broad spectrum or selective D2, D3 or D4 agonists consistently failed to elicit significant hindlimb movements. Overall, the results clearly show in mice the existence of a role for D1 receptors in spinal network activation and corresponding rhythmic movement generation.

Role of spinal 5-HT2 receptor subtypes in quipazine-induced hindlimb movements after a low-thoracic spinal cord transection.

A role of serotonin receptors (5-HTRs) in spinal rhythmogenesis has been proposed several years ago based mainly upon data showing that bath-applied 5-HT could elicit locomotor-like rhythms in in vitro isolated spinal cord preparations. Such a role was partially confirmed in vivo after revealing that systemically administered 5-HTR(2) agonists, such as quipazine, could induce some locomotor-like movements (LM) in completely spinal cord-transected (Tx) rodents. However, given the limited binding selectivity of currently available 5-HTR(2) agonists, it has remained difficult to determine clearly if one receptor subtype is specifically associated with LM induction. In situ hybridization, data using tissues from L1-L2 spinal cord segments, where critical locomotor network elements have been identified in mice, revealed greater 5-HTR(2A) mRNA levels in low-thoracic Tx than non-Tx animals. This expression level remained elevated for several days, specifically in the lateral intermediate zone, where peak values were detected at 1 week post-Tx and returned to normal at 3 weeks post-Tx. Behavioral and kinematic analyses revealed quipazine-induced LM in 1-week Tx mice either non-pretreated or pretreated with selective 5-HTR(2B) and/or 5-HTR(2C) antagonists. In contrast, LM completely failed to be induced by quipazine in animals pretreated with selective 5-HTR(2A) antagonists. Altogether, these results provide strong evidence suggesting that 5-HTR(2A) are specifically associated with spinal locomotor network activation and LM generation induced by quipazine in Tx animals. These findings may contribute to design drug treatments aimed at promoting locomotor function recovery in chronic spinal cord-injured patients.

Effects of spinal alpha(2)-adrenoceptor and I(1)-imidazoline receptor activation on hindlimb movement induction in spinal cord-injured mice.

A partial recovery of locomotor functions has been shown in spinal cord-transected (Tx) cats after regular treadmill training and repeated administration of clonidine, an alpha(2)-adrenoreceptor agonist. However, clonidine has generally failed to show prolocomotor effects in other models (e.g., rat or mudpuppy in vitro-isolated spinal cord preparations). The reasons for this discrepancy remain unclear, but they may suggest condition- or species-specific effects induced by clonidine. This study is aimed at examining both the acute (at 6 or 41 days post-Tx) and chronic effects of repeated (once a week for one month) clonidine administration (0.25-5.0 mg/kg i.p.) on hindlimb movement generation in Tx mice (thoracic segment9/10). Locomotor-like (LM) and nonlocomotor movements (NLM) were assessed both in open-field and treadmill conditions. The results show that clonidine consistently failed, in both conditions, to induce LM and NLM at all time points even though control experiments revealed hindlimb movements steadily induced by 8-hydroxy-2-(di-N-propylamino)-tetralin (8-OH-DPAT), a serotonin receptor agonist. In turn, clonidine acutely suppressed (I(1)-imidazoline receptor-mediated) the frequency of spontaneously occurring LM and NLM but apparently increased spinal excitability over time, because the frequency of spontaneous LM and NLM was significantly greater in clonidine-treated (before an injection) than vehicle-treated animals after repeated administration for a few weeks. The results clearly show that clonidine can not acutely induce hindlimb movements in untrained and otherwise nonstimulated (e.g., no tail or perineal pinching) Tx mice, although repeated administration may progressively facilitate the expression of spontaneous hindlimb movements.

Tail pinching-induced hindlimb movements are suppressed by clonidine in spinal cord injured mice.

Experiments in completely spinal cord transected (Tx) cats have provided compelling evidence that clonidine combined with tail stimulation can promote locomotor function recovery. However, clonidine has generally failed to induce locomotor activity in other comparable animal models suggesting the existence of species- or condition-specific effects. This study aimed at investigating the effects of clonidine administered (0.25 or 5.0 mg/kg, i.p.) in mice during tail pinching in early (6-7 days post-Tx) or late (41-42 days post-Tx) paraplegic animals (Th9/10 level). Comparisons were made with the effects induced by 8-OH-DPAT (1.0 mg/kg, i.p.), a 5-HT1A/7 receptor agonist known to display prolocomotor effects. Clonidine with or without tail pinching failed to induce hind limb movements and even suppressed the frequency of spontaneously occurring nonlocomotor (NLM) and locomotor-like movements (LM) whereas tail pinching alone (prior to clonidine administration) increased the frequency of spontaneous movements specifically in late chronic animals. In turn, 8-OH-DPAT clearly induced hind limb movements that remained relatively unchanged during tail pinching. Altogether, the results suggest that the prolocomotor effects of clonidine reported elsewhere must depend upon stimuli or factors that remain to be identified.

Intact primate brain tissue identification using a completely fibered coherent Raman spectroscopy system.

Coherent Raman fiber probes have not yet found their way into the clinic despite their immense potential for label-free sensing and imaging. This is mainly due to the traditional bulky laser systems required to create the high peak power laser pulses needed for coherent Raman, as well as the complications that arise from the propagation of this type of energy through silica. Specifically, a coherent anti-Stokes Raman scattering (CARS) probe that could select its integration volume at high resolution, away from the tip of the fiber, is particularly interesting in the case of electrode implantation neurosurgeries, wherein it is possible to place optical fibers on-board the chronic electrode and provide optical guidance during its implantation, through the semi-transparent tip. To this clinical end, we have created an all fiber CARS system, consisting of small, rapidly tunable, turn-key fiber-lasers, capable of creating high wavenumber CARS spectra on the order of tens-of-milliseconds. The use of traditional silica fibers is made possible by the use of the laser's long pulse-widths (25 ps). The probe itself has an outer diameter of 250 µm allowing it to fit within commercially available metal tubes that can replace deep brain stimulation (DBS) stylets. Using this system, we identified brain tissue types in intact nonhuman primates' brains and showed the ability to delineate white and gray matters with high resolution. Its advantages over spontaneous Raman stem from the orders of magnitude improvement in spatial resolution, its inherent translatability to three-dimensional (3-D) imaging, as well as the theoretical ability to remove parasitic Raman signal from probe encasements, such as a DBS electrode. The system is planned to have clinical implications in neurosurgical guidance as well as diseased tissue detection.

Hormonal and immunological changes in mice after spinal cord injury.

Spinal cord injury (SCI) is associated with immune deficiencies and life-threatening infections. However, the specific mechanisms underlying this pathological condition remain unclear. In recent years, increasing evidence has suggested that anabolic hormones may be involved in immunological complications. Here, we monitored candidate hormone concentrations and immune cell counts, in CD1 mice, for 4 weeks after low-thoracic transection of the spinal cord (Tx). Serum dihydroepiandrosterone (DHEA), insulin, and parathyroid hormone (PTH) levels decreased throughout the time period studied compared with control, non-Tx mice. In turn, testosterone and growth hormone (GH) levels were only transiently changed, with a decrease of testosterone during the first 2 weeks and an increase of GH at 1 week post-Tx. A complete blood count revealed either unchanged or moderately decreased erythrocyte, platelet, hemoglobin and hematocrit levels. Total leukocyte, lymphocyte, and eosinophil counts also decreased, whereas neutrophils and monocytes did not change significantly. In the bone marrow, lymphocyte numbers decreased and neutrophils increased, whereas monocytes, eosinophils, and megakariocytes did not change significantly. These results revealed significant changes occurring rapidly (<1-2 weeks) after Tx in both hormonal and immunological systems, providing compelling evidence of a role for anabolic hormones in SCI-related immune deficiencies.

In vitro gastric survival of commercially available probiotic strains and oral dosage forms.

Although the intestinal microbial community is still incompletely understood, there is strong evidence of the benefits of using probiotics to address some medical states or conditions. As a result, the probiotics oral supplements market has exploded during the last few years. However, while their sensitivity to gastric juices, acidic pH and bile is well known, most of these oral forms would not guarantee any survival of the strains in such conditions. In this work, we have studied the resistance to simulated gastric juices of several commercially available probiotics products. These included sixteen strains and ten oral forms such as enteric/non-enteric capsules/tablets and microencapsulated strains. Results demonstrated that all tested strains showed high sensitivity to acidic conditions and suggested that most of these microorganisms would not show any viability when immersed in the stomach at fasting. Most probiotics oral forms did not provide any protection to strains, unless these forms presented strong enteric protection. Consequently, the efficacy of non-enteric products to fully provide to the patient the benefits related to the consumption of probiotics supplement would be strongly questionable. This study underlines the chasm between the current opinion about probiotics protection needs and the products proposed by many companies in the dietary supplements area.

Strain-dependent recovery of spontaneous hindlimb movement in spinal cord transected mice (CD1, C57BL/6, BALB/c).

Reorganization and plasticity after spinal cord injury have been recently shown to take place in sublesional neuronal networks, but the possibility of strain-dependent changes at that level has never been explored. The authors studied the spontaneous return of hindlimb movement in low-thoracic spinal cord transected (Tx) mice from 3 commonly used strains. Without intervention, most CD1, C57BL/6, and BALB/c mice displayed some hindlimb movement recovery after Tx. Although all assessment methods unanimously reported that CD1 displayed higher recovery levels than did the C57BL/6 and BALB/c, higher scores were generally found with the Antri-Orsal-Barthe (M. Antri, D. Orsal, & J. Y. Barthe, 2002) and the Average Combined Score (P. A. Guertin, 2005a) methods. Such spontaneous recovery in low-thoracic Tx mice is likely the result of neuronal plasticity at the lumbosacral spinal cord level, suggesting that these sublesional changes are strain dependent.

Rotenone induces non-specific central nervous system and systemic toxicity.

We investigated the dopaminergic (DA) neuronal degeneration in animals subjected to systemic treatment of rotenone via subcutaneous delivery. Behavioral observations revealed a hypokinetic period in rats sacrificed at 3 and 5 days, and dystonic episodes in animals sacrificed at 8 days. Less than 20% of the total number of animals given rotenone depicted brain lesions after 8 days of treatment, as demonstrated by a significant loss of DA fibers in the striatum, but not of DA nigral neurons. Tyrosine hydroxylase-negative striatal territories were characterized by post-synaptic toxicity as demonstrated by a decreased number of interneurons labeled for choline acetyltransferase, NADPH-diaphorase, parvalbumin, and projection neurons labeled for calbindin and nerve growth factor inducible-B (NGFI-B). Post-synaptic neurodegeneration was demonstrated further by abundant striatal staining for Fluoro-Jade. Decrease in the nuclear orphan receptor Nurr1 expression was the only significant change observed at the level of the substantia nigra. Autopsy reports confirmed that animals suffered from severe digestion problems. These data suggest that hypokinesia observed between 3 and 5 days is the result of general health problems rather than a specific motor deficit associated to Parkinson's disease (PD) symptoms. Overall, the effects of rotenone toxicity are widespread, and subcutaneous administration of this toxin does not provide the neuropathological and behavioral basis for a relevant and reliable PD model.

Clear as mud: a meta-analysis on the effects of sedimentation on freshwater fish and the effectiveness of sediment-control measures.

Increase in fine sediments in freshwater resulting from anthropogenic development is a potential stressor for fish and thus may cause population declines. Though a large body of literature exists on the topic, there have been few attempts to synthesize this information in a quantitative manner. Through meta-analysis we investigated the effects of sediment in lotic environments on resident ichthyofauna using ecologically-relevant endpoints for tolerant (e.g., northern pike Esox lucius) and intolerant (e.g., brook trout Salvelinus fontinalis) species. Further, the efficiency of sediment-control devices was explored to inform mitigation measures. An increase in suspended and deposited sediments was demonstrated to have a negative effect on all parameters and tolerances tested (feeding behavior [feeding rate, reaction distance to food item]; spawning success [survival of fry to eyed stage, fry emergence]; species richness; P < 0.001) except fish abundance (P = 0.058). Heterogeneity between studies was a factor in all analyses. Although there were insufficient studies to conduct meta-analysis on sediment-control devices, weighted percent efficiency estimates revealed that properly installed sediment-control fences tended to have a higher percent efficiency (73-80%) than sediment traps and basins (40-52%). These results highlight the negative impact that increases in suspended and deposited sediments can have on resident fishes from the individual to the population, and the need for more transparent and thorough statistical reporting. The analysis also identifies a clear need for rigorous experimental studies contrasting different sediment-control devices and strategies given that little such work has been published. That alone is remarkable given that sediment-control devices are often a requirement of regulators for riparian development activities, yet the evidence to support the effectiveness of the primary mitigative strategies is weak.

Synergistic effects of D1/5 and 5-HT1A/7 receptor agonists on locomotor movement induction in complete spinal cord-transected mice.

Monoamines are well known to modulate locomotion in several vertebrate species. Coapplication of dopamine (DA) and serotonin (5-HT) has also been shown to potently induce fictive locomotor rhythms in isolated spinal cord preparations. However, a synergistic contribution of these monoamines to locomotor rhythmogenesis in vivo has never been examined. Here, we characterized the effects induced by selective DA and 5-HT receptor agonists on hindlimb movement induction in completely spinal cord transected (adult) mice. Administration of the lowest effective doses of SKF-81297 (D 1/5 agonist, 1-2 mg/kg, ip) or 8-OH-DPAT (5-HT 1A/7 agonist, 0.5 mg/kg, ip) acutely elicited some locomotor-like movements (LM) (5.85 +/- 1.22 and 3.67 +/- 1.44 LM/min, respectively). Coadministration of the same doses of SKF-81297 and 8-OH-DPAT led to a significant increase (7- to 10-fold) of LM (37.70 +/- 5.01 LM/min). Weight-bearing and plantar foot placement capabilities were also found with the combination treatment only (i.e., with no assistance or other forms of stimulation). These results clearly show that D 1/5 and 5-HT 1A/7 receptor agonists can synergistically activate spinal locomotor networks and thus generate powerful basic stepping movements in complete paraplegic animals. Although previous work from this laboratory has reported the partial rhythmogenic potential of monoamines in vivo, the present study shows that drug combinations such as SKF-81297 and 8-OH-DPAT can elicit weight-bearing stepping.

Histomorphometric and densitometric changes in the femora of spinal cord transected mice.

Spinal cord injury (SCI) leads generally to significant bone tissue loss within a few months to a few years post-trauma. Although, increasing data from rat models are available to study the underlying mechanisms of SCI-associated bone loss, little is known about the extent and rapidity of bone tissue changes in mouse models of SCI. The objectives are to characterize and describe quantitatively femoral bone tissue changes during 1 month in adult paraplegic mice. Histomorphometric and densitometric measurements were performed in 3- to 4-month-old CD1 mice spinal cord transected at the low-thoracic level (Th9/10). We found a general decrease in bone volume (-22%), trabecular thickness (-10%), and trabecular number (-14%) within 30 days post-transection. Dual-energy X-ray absorptiometric measurements revealed no change in bone mineral density but a significant reduction (-14%) in bone mineral content. These results show large structural changes occurring within only a few weeks post-spinal cord transection in the femora of adult mice. Given the increasing availability of genetic and molecular research tools for research in mice, this murine model may be useful to study further the cellular and molecular mechanisms of demineralization associated with SCI.

Plasticity in sublesionally located neurons following spinal cord injury.

Neuronal plasticity has been traditionally associated with learning and memory processes in the hippocampal regions of the brain. It is now generally accepted that plasticity phenomena are also associated with other kinds of cellular changes and modifications occurring in all areas of the CNS after injury or intense neuronal activity. For instance, spinal cord injuries have been associated with a series of cellular modifications and adaptations taking place distally in sublesional areas. Some of these modifications include changes in the expression of immediate early genes (e.g., c-fos and nor-1), TNF-alpha, preprodynorphin, neurotrophic factors (e.g., BDNF and NT-3), and several subtypes of transmembranal receptors (e.g., 5-HT(1A) and 5-HT(2A)). This review constitutes an update of the current knowledge regarding this broadly defined plasticity phenomenon that occurs spontaneously or can be modulated by training in sublesional segments of the spinal cord. Spinal cord plasticity is an increasingly popular field of research, believed by many as being a complex phenomenon that may contribute to the development of innovative therapeutics and rehabilitative approaches for spinal cord injured patients.

Contribution of spinal 5-HT1A and 5-HT7 receptors to locomotor-like movement induced by 8-OH-DPAT in spinal cord-transected mice.

Growing evidence from in vitro studies suggests that spinal serotonin (5-HT) receptor subtypes 5-HTR(1A) and 5-HTR(7) are associated with an induction of central pattern generator activity. However, the possibility of a specific role for these receptor subtypes in locomotor rhythmogenesis in vivo remains unclear. Here, we studied the effects of a single dose (1 mg/kg, i.p.) of 8-hydroxy-2-(di-N-propylamino)-tetralin (8-OH-DPAT), a potent and selective 5-HTR(1A/7) agonist, in mice spinal cord transected at the low-thoracic level (Th9/10). The results show that 8-OH-DPAT acutely induced, within 15 min, hindlimb movements that share some characteristics with normal locomotion. Paraplegic mice pretreated with the selective 5-HTR(1A) antagonists, WAY100,135 or WAY100,635, displayed significantly less 8-OH-DPAT-induced movement. A similar reduction of 8-OH-DPAT-induced movements was found in animals pretreated with SB269970, a selective 5-HTR(7) antagonist. Moreover, a near complete blockade of 8-OH-DPAT-induced movement was obtained in wild-type mice pretreated with 5-HTR(1A) and 5-HTR(7) antagonists, and in 5-HTR(7)-/- mice pretreated with 5-HTR(1A) antagonists. Overall, these results clearly demonstrate that 8-OH-DPAT potently induces locomotor-like movement in the previously paralysed hindlimbs of low-thoracic-transected mice. The results, with selective antagonists and knockout animals, provide compelling evidence of a specific contribution of both receptor subtypes to spinal locomotor rhythmogenesis in vivo.

Systemic exposure to paraquat and maneb models early Parkinson's disease in young adult rats.

In recent years, several lines of evidence have shown an increase in Parkinson's disease (PD) prevalence in rural environments where pesticides are widely used. Paraquat (PQ--herbicide) and maneb (MB--fungicide) are among the compounds suspected to induce neuronal degeneration and motor deficits characteristics of PD. Here, we investigated the effects of PQ and MB on dopaminergic (DA) neuron-glia cultures and in vivo in young adult rats. In vitro, PQ led to a loss of DA as compared to non-DA neurons and microglial activation in a dose-dependent manner. Addition of MB had no further effect nor did it lead to microglial activation when used alone. In vivo, 2-month old young adult rats were subjected to intraperitoneal injections of vehicle (n = 4), PQ alone (n = 8), or PQ in combination with MB (n = 8) twice a week for 4 weeks and were sacrificed the day following the last injection. Significant loss of nigral DA neurons was observed in both treatment groups, but a significant decrease in striatal DA fibers was not found. Microglial activation was seen in the nigra of rats subjected to PQ with or without MB. Behavioral analyses demonstrated a mixed pattern of motor impairments, which may have been related to early effects of nigral DA neuronal loss or systemic effects associated with MB exposure in addition to PQ. These results indicate that exposure to PQ with or without MB induces neurodegeneration which might occur via an early inflammatory response in young adult animals.